CAMBRIDGE, Mass., Oct 30, 2010 (BUSINESS WIRE) -- Idera Pharmaceuticals, Inc. /quotes/comstock/15*!idra/quotes/nls/idra (IDRA 2.76, -0.03, -1.08%) announced today the presentation of data from a Phase 1 clinical trial evaluating IMO-2125, a novel immune modulator, in null-responder patients with chronic hepatitis C virus (HCV) infection. The oral presentation, entitled "IMO-2125, a TLR9 Agonist, Induces Immune Responses which Correlate with Reductions in Viral Load in Null-Responder HCV Patients" (Abstract #33), is being made by Maribel Rodriguez-Torres, M.D., of Fundacion de Investigacion in Santurce, Puerto Rico at the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD).
"Null-responder patients are the most difficult HCV patients to treat and represent an area of significant need as there are currently no approved treatment options for these patients," said Dr. Rodriguez-Torres. "The data presented show that IMO-2125 induced a broad immune response including induction of endogenous interferons. This suggests that IMO-2125 may provide an alternative to the recombinant interferon component of HCV treatment."
This Phase 1 clinical trial evaluated 51 null-responder HCV patients; 41 patients received IMO-2125 monotherapy at five dose levels and 10 patients received placebo once per week for four weeks. Most of these patients were infected with HCV genotype 1 and had the CT or TT IL28B gene alleles. IMO-2125 was well tolerated at all dose levels. IMO-2125 induced a broad immune response with dose-dependent increases in serum concentrations of antiviral proteins and activation of cellular immune responses. Across the three highest dose levels, seventy-five percent of patients achieved a 1 log10 or greater decrease in viral load at least once during the treatment period. Consistent with the proposed mechanism of IMO-2125, induction of higher serum concentrations of interferon-alpha correlated with greater decreases in HCV viral load. Additional patients are being enrolled in this Phase 1 trial to evaluate twice-weekly dosing of IMO-2125.
"These data demonstrate that in the trial once-weekly dosing of IMO-2125 in null-responders induced a distinctive pattern of immune activation and achieved dose-dependent viral load reductions," said Robert Arbeit, M.D., VP of Clinical Development of Idera Pharmaceuticals. "To optimize the dosing schedule and maximize antiviral activity we are continuing the trial to evaluate twice-weekly dosing of IMO-2125."
Dr. Arbeit continued, "In addition, we are conducting a Phase 1 trial in treatment-naive HCV patients evaluating IMO-2125 at multiple dose levels using both once-weekly and twice-weekly dosing regimens for four weeks in combination with ribavirin, compared to a control arm of patients receiving pegylated recombinant interferon-alpha and ribavirin. We expect to report top-line data from this trial in the fourth quarter."
"The data presented from this trial support the target product profile of IMO-2125 as a novel immune modulator with the potential to be used as a key component of HCV treatment," said Sudhir Agrawal, D.Phil., Chairman and Chief Executive Officer at Idera. "Prior to initiating a Phase 2 clinical trial for IMO-2125, we plan to analyze the full data sets from the ongoing Phase 1 IMO-2125 trials and evaluate the upcoming changes in the development and treatment landscape for HCV. We expect that, after assessing these factors, we will outline our clinical development strategy and plans for a Phase 2 program for IMO-2125 by the end of 2010."
Phase 1 Clinical Trial in Null-Responder HCV Patients
Study Design:
IMO-2125 was administered subcutaneously once per week for four weeks at five dose levels of 0.04, 0.08, 0.16, 0.32 and 0.48 mg/kg. The clinical trial was designed to evaluate safety, immunological activity and reduction in HCV viral load. Eight patients were enrolled at each dose level with an additional two patients randomized to receive placebo treatment for a total of 10 per cohort. All patients enrolled in the trial were null-responders, defined as patients who failed to achieve a 2 log10 reduction in viral load with 12 to 24 weeks of previous treatment with pegylated recombinant interferon-alpha plus ribavirin.
Study Results:
Patient Population
This Phase 1 clinical trial evaluated 51 null-responder HCV patients; 41 patients received IMO-2125 monotherapy and 10 patients received placebo. Patients were predominantly infected with HCV genotype 1 (98%) and over 90% were IL-28B genotypes CT or TT. At enrollment, the patients had high viral load (mean HCV RNA, 6.8 log10) and elevated levels of IP-10 (mean, 561 pg/mL). These factors are generally associated with poor response to standard of care treatment.
Safety
IMO-2125 was well tolerated for four weeks of treatment. There were no treatment-related serious adverse events (SAEs) and no treatment-related discontinuations. The most common adverse events were "flu-like symptoms" that typically lasted less than 1 day, injection site reactions and headache. There were no clinically significant adverse effects on safety laboratory parameters.
IMO-2125 Activation of Immune Response
Patients receiving IMO-2125 showed dose-dependent increases in serum concentrations of endogenous interferon-alpha, which were more pronounced after the fourth dose compared to the first dose. Patients receiving IMO-2125 showed dose-dependent increases in serum concentrations of IP-10 and 2', 5'-oligoadenylate synthetase (2', 5'-OAS), host proteins which are known to contribute to antiviral activity. Patients receiving IMO-2125 showed dose-dependent increases in cell markers of immune activation, including increases in NK cells, helper T cells and cytotoxic T cells.
HCV RNA reduction
Patients receiving IMO-2125 showed dose-dependent reduction in HCV RNA viral load. At dose levels of 0.32 and 0.48 mg/kg/week, six of eight patients and seven of eight patients, respectively, achieved a reduction in viral load of 1 log10 or more at least once during the treatment period; in both groups the median for the maximum viral load reductions was 1.6 log10. IL28B genotype data are available for 14 of the 16 patients treated with IMO-2125 at 0.32 or 0.48 mg/kg/week. Thirteen of these patients had CT or TT IL28B genotype, of which 10 had maximum viral load reductions ranging from -1 to -2.6 log10 at least once during the treatment period. The 14th patient had CC IL28B genotype and had a maximum viral load reduction of 2.5 log10 at least once during the treatment period. Serum concentrations of endogenous interferon-alpha induced by IMO-2125 treatment correlated with reductions in HCV RNA viral levels.
Authors of the presentation and study investigators include: Maribel Rodriguez-Torres, M.D., of Fundacion de Investigation, Santurce PR; Reem Ghalib, M.D., of The Liver Institute, Dallas TX; Stuart Gordon, M.D., of Henry Ford Medical Center, Novi, MI; Eric Lawitz, M.D., of Alamo Medical Research, San Antonio TX; Keyur Patel, M.D., of Duke University Medical Center, Durham NC; Ronald Pruitt, M.D., of Nashville Gastrointestinal Specialists, Nashville, TN; Aasim Sheikh, M.D., of Gastrointestinal Specialists of Georgia, Marietta GA; Andrew Muir, M.D., MHS, of Duke Clinical Research Institute, Durham, NC; John McHutchison, M.D., formerly of Duke Clinical Research Institute, Durham, NC; and Alice Bexon, MBChB, Ekambar Kandimalla, Ph.D., Melissa Precopio, Ph.D. and Tim Sullivan, Ph.D., of Idera Pharmaceuticals, Inc.
About IMO-2125
IMO-2125, a Toll-like Receptor (TLR) 9 agonist, is a novel immune modulator being developed as a component of treatment for chronic hepatitis C virus (HCV) infection. IMO-2125 is designed to stimulate the immune system, causing the body to generate natural interferons and other antiviral cytokines. IMO-2125 is currently in a Phase 1 clinical trial in null-responder HCV patients, defined as those who did not achieve a 2 log10 reduction with prior standard of care treatment, as monotherapy for 4 weeks. IMO-2125 is also being evaluated in a Phase 1 clinical trial in treatment-naive HCV patients in combination with ribavirin for 4 weeks.
About Idera Pharmaceuticals, Inc.
Idera Pharmaceuticals develops drug candidates to treat infectious diseases, autoimmune and inflammatory diseases, cancer, and respiratory diseases, and for use as vaccine adjuvants. Our proprietary drug candidates are designed to modulate specific Toll-like Receptors (TLRs), which are a family of immune system receptors that direct immune system responses. Our pioneering DNA and RNA chemistry expertise enables us to create drug candidates for our internal development programs and our partnered programs, and generates opportunities for additional collaborative alliances. For more information, visit http://www.iderapharma.com/.
Idera Forward Looking Statements
This press release contains forward-looking statements concerning Idera Pharmaceuticals, Inc. that involve a number of risks and uncertainties. For this purpose, any statements contained herein that are not statements of historical fact may be deemed to be forward-looking statements. Without limiting the foregoing, the words "believes," "anticipates," "plans," "expects," "estimates," "intends," "should," "could," "will," "may," and similar expressions are intended to identify forward-looking statements. There are a number of important factors that could cause Idera's actual results to differ materially from those indicated by such forward-looking statements; whether results obtained in preclinical studies and early clinical trials such as the trials referred to in this release will be indicative of results obtained in future clinical trials; whether products based on Idera's technology will advance into or through the clinical trial process on a timely basis or at all and receive approval from the United States Food and Drug Administration or equivalent foreign regulatory agencies; whether, if the Company's products receive approval, they will be successfully distributed and marketed; whether the Company's collaborations will be successful; whether the patents and patent applications owned or licensed by the Company will protect the Company's technology and prevent others from infringing it; whether Idera's cash resources will be sufficient to fund the Company's operations; and such other important factors as are set forth under the caption "Risk Factors" in Idera's Quarterly Report on Form 10-Q for the three months ended June 30, 2010, which important factors are incorporated herein by reference. Idera disclaims any intention or obligation to update any forward-looking statements.
SOURCE: Idera Pharmaceuticals, Inc.
Idera Pharmaceuticals, Inc.
Teri Dahlman, 617-679-5519
tdahlman@iderapharma.com
or
MacDougall Biomedical Communications
Chris Erdman, 781-235-3060
cerdman@macbiocom.com
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October 30, 2010
Vertex, Merck Drugs Help More With Faster Cure for Hepatitis C
October 30, 2010, 9:36 AM EDT
By Michelle Fay Cortez
Oct. 30 (Bloomberg) -- Vertex Pharmaceuticals Inc. and Merck & Co. said their experimental drugs for hepatitis C cured more patients than traditional treatment, and many people were able to take a shorter, less toxic course of therapy.
Two-thirds of patients given Vertex’s telaprevir were able to cut their treatment time in half to six months, and about 90 percent were cured, two studies funded by the Cambridge, Massachusetts-based company found. Nearly half of those given boceprevir in studies from Whitehouse Station, New Jersey-based Merck were able to reduce their treatment times to six months to nine months, with similar high rates of cure.
The findings presented today at the American Association for the Study of Liver Disease meeting in Boston will help usher in a new era of treatment for hepatitis C, doctors say. The chronic condition affects nearly 4 million Americans and 200 million people worldwide, according to the National Institutes of Health. The companies plan to file for U.S. regulatory approval of the drugs by the end of the year.
“The current standard of care is long and it’s not easy to take,” said Michael Charlton, director of the Mayo Clinic’s liver transplant program in Rochester, Minnesota. “The appeal of the new drugs is the shorter treatment, and you get there quicker with telaprevir,” he said in a telephone interview.
Standard Treatment
Hepatitis C often persists as a chronic condition that causes nausea, weakness and exhaustion as it destroys the liver over time. Interferon, the standard of care when paired with the generic drug ribavirin to increase potency, works by boosting the immune system. The yearlong treatment causes aches and pains similar to the flu that may last the entire year of treatment and cures about half of those who can tolerate it.
Roche Holding AG of Basel, Switzerland, sells a version of interferon under the brand name Pegasys, while Merck sells a form called PegIntron.
Telaprevir will capture about three-fourths of the demand for the new medicines, said Howard Liang, an analyst at Leerink Swann & Co. in Boston, in a telephone interview. The drug, which Vertex is developing with New Brunswick, New Jersey-based Johnson & Johnson, will generate about $2.6 billion annually by 2013, he said.
--Editors: Andrew Pollack, Donna Alvarado
To contact the reporter on this story: Michelle Fay Cortez in Minneapolis at mcortez@bloomberg.net
To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.net
Source
By Michelle Fay Cortez
Oct. 30 (Bloomberg) -- Vertex Pharmaceuticals Inc. and Merck & Co. said their experimental drugs for hepatitis C cured more patients than traditional treatment, and many people were able to take a shorter, less toxic course of therapy.
Two-thirds of patients given Vertex’s telaprevir were able to cut their treatment time in half to six months, and about 90 percent were cured, two studies funded by the Cambridge, Massachusetts-based company found. Nearly half of those given boceprevir in studies from Whitehouse Station, New Jersey-based Merck were able to reduce their treatment times to six months to nine months, with similar high rates of cure.
The findings presented today at the American Association for the Study of Liver Disease meeting in Boston will help usher in a new era of treatment for hepatitis C, doctors say. The chronic condition affects nearly 4 million Americans and 200 million people worldwide, according to the National Institutes of Health. The companies plan to file for U.S. regulatory approval of the drugs by the end of the year.
“The current standard of care is long and it’s not easy to take,” said Michael Charlton, director of the Mayo Clinic’s liver transplant program in Rochester, Minnesota. “The appeal of the new drugs is the shorter treatment, and you get there quicker with telaprevir,” he said in a telephone interview.
Standard Treatment
Hepatitis C often persists as a chronic condition that causes nausea, weakness and exhaustion as it destroys the liver over time. Interferon, the standard of care when paired with the generic drug ribavirin to increase potency, works by boosting the immune system. The yearlong treatment causes aches and pains similar to the flu that may last the entire year of treatment and cures about half of those who can tolerate it.
Roche Holding AG of Basel, Switzerland, sells a version of interferon under the brand name Pegasys, while Merck sells a form called PegIntron.
Telaprevir will capture about three-fourths of the demand for the new medicines, said Howard Liang, an analyst at Leerink Swann & Co. in Boston, in a telephone interview. The drug, which Vertex is developing with New Brunswick, New Jersey-based Johnson & Johnson, will generate about $2.6 billion annually by 2013, he said.
--Editors: Andrew Pollack, Donna Alvarado
To contact the reporter on this story: Michelle Fay Cortez in Minneapolis at mcortez@bloomberg.net
To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.net
Source
ANA598 Data Presented at AASLD Highlight Positive Clinical Profile of DAA Entering Phase IIb
Oral Presentation at 3:00 pm on October 31 at AASLD
SAN DIEGO, Oct. 30 /PRNewswire-FirstCall/ -- Anadys Pharmaceuticals, Inc. (Nasdaq: ANDS) today announced the ANA598 data to be presented at the 61st Annual Meeting of the American Association for the Study of Liver Disease (AASLD) in Boston, MA. ANA598, the Company's direct-acting antiviral (DAA) being developed for the treatment of hepatitis C, will be discussed in two presentations at the conference:
• On Sunday, October 31, 2010 at 3:00 pm Eastern Daylight Time, Eric Lawitz, M.D., a principal investigator of the study, will give an oral presentation titled, "Safety and Antiviral Activity of ANA598 in Combination with Pegylated Interferon alpha 2A Plus Ribavirin in Treatment-Naive Genotype-1 Chronic HCV Patients." The slides will be available on the Company's website at www.anadyspharma.com following conclusion of the presentation.
• On Tuesday, November 2, 2010 at 7:00 am Eastern Daylight Time, Anadys will present data in a poster titled, "IL28B Polymorphism and Kinetics of Antiviral Activity for ANA598 in Combination with Pegylated Interferon alpha 2A Plus Ribavirin in Treatment-Naive Genotype-1 Chronic HCV Patients." The poster will be available on the Company's website at www.anadyspharma.com.
"We are pleased with the positive clinical profile seen to date for ANA598, as well as its preclinical properties that support investigation of combinations with other direct antivirals," said James L. Freddo, M.D., Senior Vice President, Drug Development and Chief Medical Officer of Anadys. "In the upcoming Phase IIb study, we look forward to testing ANA598 for the first time in treatment-experienced patients, as well as in a larger population of treatment-naive patients."
In the oral presentation, data from an ongoing Phase II combination study show that ANA598 added to pegylated interferon and ribavirin (current standard of care, or SOC) accelerated the rate of patients achieving undetectable levels of virus compared to placebo plus SOC, and that the antiviral response was equivalent at 200 mg bid and 400 mg bid ANA598. The data from the study further show a durable antiviral response through 12 weeks, with only a single patient (<2% of patients in the ANA598 arms) experiencing viral breakthrough while receiving ANA598 plus SOC. The safety profile of ANA598 through 12 weeks was excellent in the study, with reported adverse events being typical for patients treated with interferon and ribavirin alone, and the incidence of rash in patients receiving ANA598 200 mg bid plus SOC in the study was comparable to the group receiving placebo plus SOC.
Additional data from the Phase II combination study will be presented reflecting the persistence of ANA598's benefit beyond week 12. 39 of 41 patients (>95%) who achieved undetectable levels of virus at week 12 in the two active arms have maintained undetectable levels while continuing to receive SOC through the latest available measurements. For patients who, per protocol, concluded all treatment at week 24, interim analysis of SVR data for available patients indicates that 8 of 11 patients maintained undetectable levels of virus 12 weeks later, referred to as a Sustained Virological Response 12, or SVR12. The three patients who relapsed after concluding treatment at week 24 demonstrated the lowest week 4 ribavirin levels of all patients who concluded treatment at week 24, consistent with the known impact of ribavirin levels on converting on-treatment response to SVR. Data is available for three patients 24 weeks after concluding treatment. All three patients achieved an SVR24, recognized as a viral cure.
In the poster presentation on Tuesday, November 2, 2010, Anadys will present additional data from the Phase II combination study showing that the addition of ANA598 to SOC conferred benefit independent of a patient's IL-28B genotype. In patients with the IL-28B genotype most responsive to SOC (referred to as CC), ANA598 accelerated the rate of achieving undetectable levels of virus, with 82% of patients who received ANA598 plus SOC achieving undetectable levels by week 4, compared to 27% of patients who received placebo plus SOC. In patients with IL-28B genotypes less responsive to SOC (referred to as CT and TT, or collectively non-CC), ANA598 both accelerated the rate of achieving undetectable levels of virus and increased the percentage of patients with undetectable levels of virus at week 12. In the non-CC patients, 38% of patients who received ANA598 plus SOC achieved undetectable levels of virus by week 4, compared to 8% of patients who received placebo plus SOC, and 73% of patients who received ANA598 plus SOC achieved undetectable levels of virus at week 12, compared to 47% of patients who received placebo plus SOC.
Phase II Combination Study
In the ongoing Phase II study, approximately 90 treatment-naive genotype 1 HCV patients have received ANA598 or placebo in combination with Pegasys® (peginterferon alfa-2a) and Copegus® (ribavirin, USP) for 12 weeks at dose levels of 200 mg twice-daily (bid) or 400 mg bid, each with a loading dose of 800 mg bid on day one. After week 12, patients are to continue receiving SOC. Patients who achieved undetectable levels of virus at weeks 4 and 12 were randomized to stop all treatment at week 24 or 48. The primary endpoint of the study is the proportion of patients who achieve undetectable levels of virus at week 12 (defined as complete Early Virological Response, or cEVR). Additional endpoints include safety and tolerability as well as the proportion of patients with undetectable levels of virus at week 4 (defined as Rapid Virological Response, or RVR). Patients are being followed for 24 weeks after stopping therapy to determine the rate of Sustained Virological Response, or SVR. Approximately 90 patients have been enrolled in this study – with approximately 30 patients receiving ANA598 plus SOC at each dose level and 30 patients receiving placebo plus SOC. The study is being managed by the Duke Clinical Research Institute (DCRI) and is being conducted at a number of clinical sites in the United States.
About Anadys
Anadys Pharmaceuticals, Inc. is a biopharmaceutical company dedicated to improving patient care by developing novel medicines for the treatment of hepatitis C. The Company believes hepatitis C represents a large unmet medical need in which meaningful improvements in treatment outcomes may be attainable with the introduction of new medicines. Anadys is preparing to initiate a Phase IIb study of ANA598, the Company's direct-acting antiviral or DAA, added to current standard of care for the treatment of hepatitis C. The Company is also preparing to resume clinical development of ANA773, the Company's oral, small-molecule inducer of endogenous interferons that acts via the Toll like receptor 7, or TLR7, pathway in hepatitis C.
Safe Harbor Statement
Statements in this press release that are not strictly historical in nature constitute "forward-looking statements." Such statements include, but are not limited to, references to (i) the plans and trial design for the planned ANA598 Phase IIb study; (ii) the belief that the preclinical properties of ANA598 support investigation of combinations with other direct antivirals and the ability to pursue such combinations; (iii) assessments of the potency, safety and tolerability profile of ANA598 based on the 12 week results; (iv) the durability of antiviral response after treatment with ANA598 is concluded as well as interim SVR rates based on data available to date; and (v) the beneficial effect of ANA598 in both CC and non-CC patients based on observations in the Phase II combination study. Such forward-looking statements involve known and unknown risks, uncertainties and other factors, which may cause Anadys' actual results to be materially different from historical results or from any results expressed or implied by such forward-looking statements. For example, the results of preclinical and early clinical studies may not be predictive of future results, and Anadys cannot provide any assurances that ANA598 or ANA773 will not have unforeseen safety issues, will have favorable results in future clinical trials or will receive regulatory approval. In addition, Anadys' results may be affected by competition from other biotechnology and pharmaceutical companies, its effectiveness at managing its financial resources, its ability to enter into transactions around its product candidates, its ability to successfully develop and market products, difficulties or delays in its preclinical studies or clinical trials, difficulties or delays in manufacturing its clinical trials materials, the scope and validity of patent protection for its products, regulatory developments and its ability to obtain additional funding to support its operations. Risk factors that may cause actual results to differ are more fully discussed in Anadys' SEC filings, including Anadys' Form 10-K for the year ended December 31, 2009, Form 10-Q for the quarter ended September 30, 2010 and Form 8-K filed on October 15, 2010. All forward-looking statements are qualified in their entirety by this cautionary statement. Anadys is providing this information as of this date and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.
Pegasys® and Copegus® are registered trademarks of Hoffman-La Roche Inc.
SOURCE Anadys Pharmaceuticals, Inc.
RELATED LINKS
http://www.anadyspharma.com/
Source
SAN DIEGO, Oct. 30 /PRNewswire-FirstCall/ -- Anadys Pharmaceuticals, Inc. (Nasdaq: ANDS) today announced the ANA598 data to be presented at the 61st Annual Meeting of the American Association for the Study of Liver Disease (AASLD) in Boston, MA. ANA598, the Company's direct-acting antiviral (DAA) being developed for the treatment of hepatitis C, will be discussed in two presentations at the conference:
• On Sunday, October 31, 2010 at 3:00 pm Eastern Daylight Time, Eric Lawitz, M.D., a principal investigator of the study, will give an oral presentation titled, "Safety and Antiviral Activity of ANA598 in Combination with Pegylated Interferon alpha 2A Plus Ribavirin in Treatment-Naive Genotype-1 Chronic HCV Patients." The slides will be available on the Company's website at www.anadyspharma.com following conclusion of the presentation.
• On Tuesday, November 2, 2010 at 7:00 am Eastern Daylight Time, Anadys will present data in a poster titled, "IL28B Polymorphism and Kinetics of Antiviral Activity for ANA598 in Combination with Pegylated Interferon alpha 2A Plus Ribavirin in Treatment-Naive Genotype-1 Chronic HCV Patients." The poster will be available on the Company's website at www.anadyspharma.com.
"We are pleased with the positive clinical profile seen to date for ANA598, as well as its preclinical properties that support investigation of combinations with other direct antivirals," said James L. Freddo, M.D., Senior Vice President, Drug Development and Chief Medical Officer of Anadys. "In the upcoming Phase IIb study, we look forward to testing ANA598 for the first time in treatment-experienced patients, as well as in a larger population of treatment-naive patients."
In the oral presentation, data from an ongoing Phase II combination study show that ANA598 added to pegylated interferon and ribavirin (current standard of care, or SOC) accelerated the rate of patients achieving undetectable levels of virus compared to placebo plus SOC, and that the antiviral response was equivalent at 200 mg bid and 400 mg bid ANA598. The data from the study further show a durable antiviral response through 12 weeks, with only a single patient (<2% of patients in the ANA598 arms) experiencing viral breakthrough while receiving ANA598 plus SOC. The safety profile of ANA598 through 12 weeks was excellent in the study, with reported adverse events being typical for patients treated with interferon and ribavirin alone, and the incidence of rash in patients receiving ANA598 200 mg bid plus SOC in the study was comparable to the group receiving placebo plus SOC.
Additional data from the Phase II combination study will be presented reflecting the persistence of ANA598's benefit beyond week 12. 39 of 41 patients (>95%) who achieved undetectable levels of virus at week 12 in the two active arms have maintained undetectable levels while continuing to receive SOC through the latest available measurements. For patients who, per protocol, concluded all treatment at week 24, interim analysis of SVR data for available patients indicates that 8 of 11 patients maintained undetectable levels of virus 12 weeks later, referred to as a Sustained Virological Response 12, or SVR12. The three patients who relapsed after concluding treatment at week 24 demonstrated the lowest week 4 ribavirin levels of all patients who concluded treatment at week 24, consistent with the known impact of ribavirin levels on converting on-treatment response to SVR. Data is available for three patients 24 weeks after concluding treatment. All three patients achieved an SVR24, recognized as a viral cure.
In the poster presentation on Tuesday, November 2, 2010, Anadys will present additional data from the Phase II combination study showing that the addition of ANA598 to SOC conferred benefit independent of a patient's IL-28B genotype. In patients with the IL-28B genotype most responsive to SOC (referred to as CC), ANA598 accelerated the rate of achieving undetectable levels of virus, with 82% of patients who received ANA598 plus SOC achieving undetectable levels by week 4, compared to 27% of patients who received placebo plus SOC. In patients with IL-28B genotypes less responsive to SOC (referred to as CT and TT, or collectively non-CC), ANA598 both accelerated the rate of achieving undetectable levels of virus and increased the percentage of patients with undetectable levels of virus at week 12. In the non-CC patients, 38% of patients who received ANA598 plus SOC achieved undetectable levels of virus by week 4, compared to 8% of patients who received placebo plus SOC, and 73% of patients who received ANA598 plus SOC achieved undetectable levels of virus at week 12, compared to 47% of patients who received placebo plus SOC.
Phase II Combination Study
In the ongoing Phase II study, approximately 90 treatment-naive genotype 1 HCV patients have received ANA598 or placebo in combination with Pegasys® (peginterferon alfa-2a) and Copegus® (ribavirin, USP) for 12 weeks at dose levels of 200 mg twice-daily (bid) or 400 mg bid, each with a loading dose of 800 mg bid on day one. After week 12, patients are to continue receiving SOC. Patients who achieved undetectable levels of virus at weeks 4 and 12 were randomized to stop all treatment at week 24 or 48. The primary endpoint of the study is the proportion of patients who achieve undetectable levels of virus at week 12 (defined as complete Early Virological Response, or cEVR). Additional endpoints include safety and tolerability as well as the proportion of patients with undetectable levels of virus at week 4 (defined as Rapid Virological Response, or RVR). Patients are being followed for 24 weeks after stopping therapy to determine the rate of Sustained Virological Response, or SVR. Approximately 90 patients have been enrolled in this study – with approximately 30 patients receiving ANA598 plus SOC at each dose level and 30 patients receiving placebo plus SOC. The study is being managed by the Duke Clinical Research Institute (DCRI) and is being conducted at a number of clinical sites in the United States.
About Anadys
Anadys Pharmaceuticals, Inc. is a biopharmaceutical company dedicated to improving patient care by developing novel medicines for the treatment of hepatitis C. The Company believes hepatitis C represents a large unmet medical need in which meaningful improvements in treatment outcomes may be attainable with the introduction of new medicines. Anadys is preparing to initiate a Phase IIb study of ANA598, the Company's direct-acting antiviral or DAA, added to current standard of care for the treatment of hepatitis C. The Company is also preparing to resume clinical development of ANA773, the Company's oral, small-molecule inducer of endogenous interferons that acts via the Toll like receptor 7, or TLR7, pathway in hepatitis C.
Safe Harbor Statement
Statements in this press release that are not strictly historical in nature constitute "forward-looking statements." Such statements include, but are not limited to, references to (i) the plans and trial design for the planned ANA598 Phase IIb study; (ii) the belief that the preclinical properties of ANA598 support investigation of combinations with other direct antivirals and the ability to pursue such combinations; (iii) assessments of the potency, safety and tolerability profile of ANA598 based on the 12 week results; (iv) the durability of antiviral response after treatment with ANA598 is concluded as well as interim SVR rates based on data available to date; and (v) the beneficial effect of ANA598 in both CC and non-CC patients based on observations in the Phase II combination study. Such forward-looking statements involve known and unknown risks, uncertainties and other factors, which may cause Anadys' actual results to be materially different from historical results or from any results expressed or implied by such forward-looking statements. For example, the results of preclinical and early clinical studies may not be predictive of future results, and Anadys cannot provide any assurances that ANA598 or ANA773 will not have unforeseen safety issues, will have favorable results in future clinical trials or will receive regulatory approval. In addition, Anadys' results may be affected by competition from other biotechnology and pharmaceutical companies, its effectiveness at managing its financial resources, its ability to enter into transactions around its product candidates, its ability to successfully develop and market products, difficulties or delays in its preclinical studies or clinical trials, difficulties or delays in manufacturing its clinical trials materials, the scope and validity of patent protection for its products, regulatory developments and its ability to obtain additional funding to support its operations. Risk factors that may cause actual results to differ are more fully discussed in Anadys' SEC filings, including Anadys' Form 10-K for the year ended December 31, 2009, Form 10-Q for the quarter ended September 30, 2010 and Form 8-K filed on October 15, 2010. All forward-looking statements are qualified in their entirety by this cautionary statement. Anadys is providing this information as of this date and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.
Pegasys® and Copegus® are registered trademarks of Hoffman-La Roche Inc.
SOURCE Anadys Pharmaceuticals, Inc.
RELATED LINKS
http://www.anadyspharma.com/
Source
Week-24 Interim Results From Phase 2b PILLAR Study to be Presented as Late-Breaker at AASLD
- Data show high antiviral activity, safety and tolerability comparable to placebo
BOSTON, Oct. 30 /PRNewswire/ -- Tibotec Pharmaceuticals (Tibotec) announced today the company will present the results of a Week-24 planned interim analysis of the phase 2 response-guided PILLAR study in treatment-naive patients with chronic genotype 1 hepatitis C virus (HCV) at the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston, MA., USA. The data will be presented as part of a late-breaker oral presentation on Monday, November 1.
The results showed that in the four TMC435 treatment groups between 79 and 86 percent of patients were able to stop all therapy at Week-24, according to the response criteria defined in the study protocol. There were no relevant differences for adverse events between TMC435 treatment groups and placebo. TMC435, a hepatitis C protease inhibitor, dosed once daily (q.d.) is being developed jointly by Tibotec Pharmaceuticals and Medivir.
The PILLAR study [Protease Inhibitor TMC435 trial assessing the optimaL dose and duration as once daiLy Anti-viral Regimen] (TMC435-C205; NCT00882908) is an ongoing, five-arm, global phase 2b randomized, double-blind, placebo controlled study in 386 treatment-naive patients. TMC435 was administered in doses of 75mg or 150mg q.d. for either 12 weeks or 24 weeks in combination with 24 weeks of peg-interferon and ribavirin (PR). Patients in the placebo arm receive 24 weeks of placebo plus peg-interferon and ribavirin followed by 24 additional weeks of peg-interferon and ribavirin treatment. The primary endpoint of the study is sustained virologic response at Week-72 (SVR24). The PILLAR study is being conducted in 13 countries in Europe, North America, and Australasia.
Patients receiving TMC435 were allowed to stop all treatment at week 24 when a) HCV RNA levels < 25 IU/mL at week 4 and b) HCV RNA < 25 IU/mL levels at weeks 12, 16 and 20. Patients who did not meet the above response-guided criteria continued with peg-interferon and ribavirin until Week-48. TMC435 demonstrated potent antiviral activity, at week 4 (rapid virologic response (RVR)) and at week 12 (complete early virologic response (cEVR)) HCV RNA was undetectable (<25IU/ml) for the majority of patients. The viral breakthrough rate was 4.9 percent in the TMC435 treatment groups.
"Chronic infection with HCV is a leading cause of cirrhosis, liver cancer, and liver transplantation worldwide," said Dr Michael W. Fried M.D., lead clinical investigator and Professor of Medicine, Director of Hepatology, University of North Carolina at Chapel Hill. "We are extremely encouraged by these data for TMC435."
The goal of HCV treatment is to achieve SVR24, which means the virus remains undetectable in patients' blood six months after they have finished treatment. Patients who achieve SVR are considered cured. The current standard of care for HCV, pegylated interferon combined with ribavirin, may cause debilitating side effects(1) and cures only about half of patients starting therapy for the first time.(1)
The most common adverse events were headache and fatigue, 46 percent and 42 percent in the TMC435 groups and 51 percent and 47 percent in the placebo group respectively. There were no clinically significant differences in frequency of rash, anemia or gastrointestinal events between the TMC435 groups and placebo. Most AEs were mild to moderate in severity. AEs leading to treatment discontinuation were reported in 7.1 percent of patients in TMC435 arms and 7.8 percent in placebo arm.
In laboratory parameters, significant decreases in transaminases (ALT and AST) were observed in all treatment groups. Small and transient bilirubin elevations (direct and indirect) were seen in the TMC435 150mg dose groups.
"With a strong heritage in virology, Tibotec is committed to improving the lives of those impacted by HCV through the development of innovative new treatment regimens," said Greg Fanning PhD, head of hepatitis C research and development at Tibotec. "TMC435 is an important component of our growing HCV pipeline and we are encouraged by the results of the interim analysis presented at the AASLD meeting."
TMC435 is also being studied in HCV genotype-1 treatment-experienced patients who have failed treatment with peg-interferon and ribavirin. The ASPIRE study (Antiviral STAT-C Protease Inhibitor Regimen in Experienced patients; TMC435-C206; NCT00980330) is an ongoing global phase 2b randomized, double-blind, placebo controlled study in 463 patients.
In addition to the late-breaker oral presentation described above, data on TMC435 has been presented in 4 posters at AASLD:
278. "In vitro studies investigating the mechanism of interaction between TMC435 and hepatic transporters." M.T. Huisman
812. "Virologic analysis of genotype-1-infected patients treated with once-daily TMC435 during the Optimal Protease inhibitor Enhancement of Response to Therapy (OPERA)-1 study." O. Lenz
895. "A Phase IIa, open-label study to assess the antiviral activity of TMC435 monotherapy in patients infected with HCV genotypes 2–6." C. Moreno
1873. "Pharmacokinetic-pharmacodynamic analyses of TMC435 in patients infected with Hepatitis C Virus (HCV) genotypes 2 to 6." V. Sekar
About HCV
HCV is a blood-borne infectious disease that affects the liver.(1) With an estimated 170 million people infected worldwide(1) and three to four million people newly infected each year,(2) HCV puts a significant burden on patients and society. Chronic infection with HCV can lead to liver cancer and other serious and fatal liver diseases, and is the most common cause of liver transplant worldwide.(3) Discovering and developing new treatments is very important to improving the standard of care for the millions of people living with this disease.
About Tibotec Pharmaceuticals
Tibotec Pharmaceuticals is a global pharmaceutical and research development company. The Company's main research and development facilities are in Beerse, Belgium with offices in Titusville, NJ and Cork, Ireland. Tibotec is dedicated to the discovery and development of innovative HIV/AIDS and hepatitis C drugs, and anti-infectives for diseases of high unmet medical need. Tibotec Pharmaceuticals is a subsidiary of Johnson & Johnson.
(1) World Health Organization (2002). Hepatitis C. Retrieved October 26, 2010 from http://www.who.int/csr/disease/hepatitis/Hepc.pdf.
(2) Hepatitis C: Global Prevalence. Weekly Epidemiological Record. 1997;72 : 341-8. Retrieved October 26, 2010 from http://www.who.int/docstore/wer/pdf/1997/wer7246.pdf.
(3) Roche B, Samuel D., Villejuif, France. Risk factors for hepatitis C recurrence after liver transplantation. J Viral Hepat. 2007 Nov;14. Suppl 1:89-96.
Contacts:
Media
Investor Relations
Karen Manson : Cell + 32 (479) 89 47 99
Stan Panasewicz : +1 732 524 2524
SOURCE Tibotec Pharmaceuticals
Source
BOSTON, Oct. 30 /PRNewswire/ -- Tibotec Pharmaceuticals (Tibotec) announced today the company will present the results of a Week-24 planned interim analysis of the phase 2 response-guided PILLAR study in treatment-naive patients with chronic genotype 1 hepatitis C virus (HCV) at the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston, MA., USA. The data will be presented as part of a late-breaker oral presentation on Monday, November 1.
The results showed that in the four TMC435 treatment groups between 79 and 86 percent of patients were able to stop all therapy at Week-24, according to the response criteria defined in the study protocol. There were no relevant differences for adverse events between TMC435 treatment groups and placebo. TMC435, a hepatitis C protease inhibitor, dosed once daily (q.d.) is being developed jointly by Tibotec Pharmaceuticals and Medivir.
The PILLAR study [Protease Inhibitor TMC435 trial assessing the optimaL dose and duration as once daiLy Anti-viral Regimen] (TMC435-C205; NCT00882908) is an ongoing, five-arm, global phase 2b randomized, double-blind, placebo controlled study in 386 treatment-naive patients. TMC435 was administered in doses of 75mg or 150mg q.d. for either 12 weeks or 24 weeks in combination with 24 weeks of peg-interferon and ribavirin (PR). Patients in the placebo arm receive 24 weeks of placebo plus peg-interferon and ribavirin followed by 24 additional weeks of peg-interferon and ribavirin treatment. The primary endpoint of the study is sustained virologic response at Week-72 (SVR24). The PILLAR study is being conducted in 13 countries in Europe, North America, and Australasia.
Patients receiving TMC435 were allowed to stop all treatment at week 24 when a) HCV RNA levels < 25 IU/mL at week 4 and b) HCV RNA < 25 IU/mL levels at weeks 12, 16 and 20. Patients who did not meet the above response-guided criteria continued with peg-interferon and ribavirin until Week-48. TMC435 demonstrated potent antiviral activity, at week 4 (rapid virologic response (RVR)) and at week 12 (complete early virologic response (cEVR)) HCV RNA was undetectable (<25IU/ml) for the majority of patients. The viral breakthrough rate was 4.9 percent in the TMC435 treatment groups.
"Chronic infection with HCV is a leading cause of cirrhosis, liver cancer, and liver transplantation worldwide," said Dr Michael W. Fried M.D., lead clinical investigator and Professor of Medicine, Director of Hepatology, University of North Carolina at Chapel Hill. "We are extremely encouraged by these data for TMC435."
The goal of HCV treatment is to achieve SVR24, which means the virus remains undetectable in patients' blood six months after they have finished treatment. Patients who achieve SVR are considered cured. The current standard of care for HCV, pegylated interferon combined with ribavirin, may cause debilitating side effects(1) and cures only about half of patients starting therapy for the first time.(1)
The most common adverse events were headache and fatigue, 46 percent and 42 percent in the TMC435 groups and 51 percent and 47 percent in the placebo group respectively. There were no clinically significant differences in frequency of rash, anemia or gastrointestinal events between the TMC435 groups and placebo. Most AEs were mild to moderate in severity. AEs leading to treatment discontinuation were reported in 7.1 percent of patients in TMC435 arms and 7.8 percent in placebo arm.
In laboratory parameters, significant decreases in transaminases (ALT and AST) were observed in all treatment groups. Small and transient bilirubin elevations (direct and indirect) were seen in the TMC435 150mg dose groups.
"With a strong heritage in virology, Tibotec is committed to improving the lives of those impacted by HCV through the development of innovative new treatment regimens," said Greg Fanning PhD, head of hepatitis C research and development at Tibotec. "TMC435 is an important component of our growing HCV pipeline and we are encouraged by the results of the interim analysis presented at the AASLD meeting."
TMC435 is also being studied in HCV genotype-1 treatment-experienced patients who have failed treatment with peg-interferon and ribavirin. The ASPIRE study (Antiviral STAT-C Protease Inhibitor Regimen in Experienced patients; TMC435-C206; NCT00980330) is an ongoing global phase 2b randomized, double-blind, placebo controlled study in 463 patients.
In addition to the late-breaker oral presentation described above, data on TMC435 has been presented in 4 posters at AASLD:
278. "In vitro studies investigating the mechanism of interaction between TMC435 and hepatic transporters." M.T. Huisman
812. "Virologic analysis of genotype-1-infected patients treated with once-daily TMC435 during the Optimal Protease inhibitor Enhancement of Response to Therapy (OPERA)-1 study." O. Lenz
895. "A Phase IIa, open-label study to assess the antiviral activity of TMC435 monotherapy in patients infected with HCV genotypes 2–6." C. Moreno
1873. "Pharmacokinetic-pharmacodynamic analyses of TMC435 in patients infected with Hepatitis C Virus (HCV) genotypes 2 to 6." V. Sekar
About HCV
HCV is a blood-borne infectious disease that affects the liver.(1) With an estimated 170 million people infected worldwide(1) and three to four million people newly infected each year,(2) HCV puts a significant burden on patients and society. Chronic infection with HCV can lead to liver cancer and other serious and fatal liver diseases, and is the most common cause of liver transplant worldwide.(3) Discovering and developing new treatments is very important to improving the standard of care for the millions of people living with this disease.
About Tibotec Pharmaceuticals
Tibotec Pharmaceuticals is a global pharmaceutical and research development company. The Company's main research and development facilities are in Beerse, Belgium with offices in Titusville, NJ and Cork, Ireland. Tibotec is dedicated to the discovery and development of innovative HIV/AIDS and hepatitis C drugs, and anti-infectives for diseases of high unmet medical need. Tibotec Pharmaceuticals is a subsidiary of Johnson & Johnson.
(1) World Health Organization (2002). Hepatitis C. Retrieved October 26, 2010 from http://www.who.int/csr/disease/hepatitis/Hepc.pdf.
(2) Hepatitis C: Global Prevalence. Weekly Epidemiological Record. 1997;72 : 341-8. Retrieved October 26, 2010 from http://www.who.int/docstore/wer/pdf/1997/wer7246.pdf.
(3) Roche B, Samuel D., Villejuif, France. Risk factors for hepatitis C recurrence after liver transplantation. J Viral Hepat. 2007 Nov;14. Suppl 1:89-96.
Contacts:
Media
Investor Relations
Karen Manson : Cell + 32 (479) 89 47 99
Stan Panasewicz : +1 732 524 2524
SOURCE Tibotec Pharmaceuticals
Source
Gilead's Investigational Hepatitis C Compounds GS 9190 and GS 9256 in Combination with Standard of Care Therapies Achieve Substantial Viral Suppression in Phase II Study
-- Compounds Among the Company's Seven HCV Pipeline Candidates Spanning Six Therapeutic Classes --
BOSTON, Oct 30, 2010 (BUSINESS WIRE) -- Gilead Sciences, Inc. /quotes/comstock/15*!gild/quotes/nls/gild (GILD 39.67, -0.19, -0.48%) today announced data from a Phase IIa study showing that its investigational compounds GS 9190 and GS 9256, used in conjunction with current standard of care therapies, produced substantial suppression of the hepatitis C virus (HCV) within 28 days of treatment. The findings are being presented Monday, November 1, during a latebreaker oral session (#LB-1) at the 61st annual meeting of the American Association for the Study of Liver Diseases (The Liver Meeting 2010) in Boston.
"Patients with chronic hepatitis C urgently need new and better treatment options, particularly combination therapies involving antiviral drugs that employ multiple mechanisms of action to eradicate the virus," said the study's principal investigator, Stefan Zeuzem, MD, JW Goethe University Hospital, Frankfurt, Germany. "The data presented today support the continued clinical evaluation of GS 9190 and GS 9256 in combination with other hepatitis C therapies and provide additional clinical insight into the effect of ribavirin in the absence of interferon."
More than seven million people in industrialized countries are chronically infected with HCV, and as many as three million Americans have the disease. The current standard of care in HCV therapy is the oral antiviral ribavirin (RBV), administered in combination with peg-interferon (Peg-IFN), which is delivered via injection and achieves a sustained therapeutic response in only 40-55 percent of patients with HCV genotype 1, the most common form of HCV in the Americas and Europe.(1)
Gilead's three-arm Phase IIa trial (Study 196-0112) evaluated the safety and efficacy of GS 9190, an oral polymerase inhibitor, in combination with GS 9256, an oral protease inhibitor, when used as: 1) a dual antiviral therapy alone; 2) a three-drug regimen with RBV; or 3) a four-drug regimen with RBV and Peg-IFN. The study found that the all-oral regimen of GS 9190, GS 9256 and RBV produced substantial viral suppression, with a median maximal decline from baseline in HCV RNA of 5.1 log10 IU/mL during 28 days of treatment. Among patients given the four-drug regimen of GS 9190, GS 9256, RBV and Peg-IFN, 100 percent (14/14 patients) achieved Rapid Virologic Response (RVR) (HCV RNA < 25 IU/mL) at day 28, with 93 percent (13/14 patients) achieving undetectable viral levels (HCV RNA < 10 IU/mL). No virologic breakthroughs were observed in this arm.
"Oral combinations of multiple antiviral agents are expected to become the new standard of care for patients with hepatitis C, and our ultimate goal and vision is to develop a potent and well-tolerated fixed-dose combination product that will eliminate the need for peg-interferon," said John McHutchison, MD, Senior Vice President for Liver Disease Therapeutics at Gilead. "These data strongly support the clinical potential of this oral combination HCV therapy, and we're looking forward to advancing the development of GS 9190 and GS 9256."
About Study 196-0112
This Phase IIa, randomized, open-label trial is evaluating GS 9190 and GS 9256 in combination (n=16), and with RBV (n=15) or with RBV/Peg-IFN (n=15). The trial enrolled treatment-naive adults with chronic HCV genotype 1 for a 28-day course of treatment. The primary outcome measures of the trial are the percentage of subjects achieving RVR, defined as HCV RNA < 25 IU/mL at Day 28, as well as the incidence of treatment-related side effects and adverse events.
Patients in the two-drug arm of the study received GS 9190 (40 mg twice daily) and GS 9256 (75 mg twice daily). Patients in the three-drug arm received a regimen of GS 9190, GS 9256 and RBV (1,000-1,200 mg total daily dose, administered twice daily), and patients in the four-drug arm also received Peg-IFN (180 g, injected once per week). In the final analysis, one patient in the four-drug arm was excluded due to a protocol violation. A median maximal decline from baseline HCV RNA of 4.1 log10 IU/mL was observed in patients receiving the two-drug combination of GS 9190 and GS 9256. The addition of RBV and RBV/Peg-IFN enhanced these responses, with median maximal RNA declines of 5.1 log10 IU/mL and 5.7 log10 IU/mL, respectively.
GS 9190 and GS 9256 were generally well tolerated. The majority of adverse events were Grade 1 or 2 in severity and resolved with continued treatment. The most common adverse events observed in each of the three arms were headache, diarrhea and nausea. Some patients taking the three-drug combination also experienced fatigue and insomnia, and some patients taking the four-drug combination experienced influenza-like illness, fatigue, myalgia and cough. There were two serious adverse events including one case of bursitis and a hospitalization for vasovagal collapse (fainting), which was attributed to gastroenteritis and occurred in a patient who continued therapy and achieved RVR. Elevations in bilirubin were observed across all three study arms, the majority of which were Grade 1 or 2 in severity and none of which resulted in study drug discontinuation.
Additional Gilead HCV Pipeline Research
In addition to Study 196-0112, data from seven additional studies will be presented at The Liver Meeting highlighting the clinical profile of the company's other HCV pipeline candidates, including another protease inhibitor, GS 9451, and a novel NS5A inhibitor, GS 5885. Gilead's HCV pipeline now includes seven unique molecules spanning six therapeutic classes with different mechanisms of action. Five of these compounds are currently in clinical trials, and two are slated to enter human clinical studies early next year.
In a Phase I three-day dose-ranging study (Study 169-0103), GS 9451 was found to be highly potent in terms of anti-HCV activity and demonstrated a long plasma half-life with once-daily dosing potential (Abstract #820). GS 9451 was tested among 33 patients with HCV genotype 1a (GT1a) or 1b (GT1b). GT1a patients received GS 9451 at 60 mg, 200 mg and 400 mg once-daily doses, and the median maximal decline from baseline in HCV RNA was 0.88, 3.2 and 3.6 log10 IU/mL, respectively. GT1b patients received GS 9451 at a 200 mg once-daily dose, and the median maximal reduction was 3.5 log10 IU/mL. The median half-life of GS 9451 at these doses ranged from 14 to 17 hours, which will allow for once-daily dosing. Treatment-emergent adverse events were generally mild to moderate. Adverse events occurring in at least two patients at any dose were headache (n=7) and dyspepsia (n=2).
Gilead also presented the first Phase I data on a novel NS5A inhibitor for HCV (Study 256-0101), GS 5885, which suggest that this compound also has once-daily dosing potential (Abstract #1883). In preclinical studies, GS 5885 demonstrated low picomolar potency and a favorable safety and pharmacokinetic profile. The clinical safety profile of GS 5885 was assessed in an escalating, single oral dose trial in 54 healthy volunteers (randomized 8:2 to receive GS 5885 versus placebo). The compound was dosed under fasted conditions at 3 mg, 10 mg, 30 mg (under fasted and fed conditions), 60 mg and 100 mg, and was well tolerated, with no serious adverse events and no treatment-emergent grade 3/4 laboratory abnormalities for one week after a single dose. Adverse events were few and generally mild, and included headache, dizziness, myalgia, dysmenorrhea and contact dermatitis from electrocardiogram (ECG) leads. GS 5885 exposure was proportional over the dosing range and produced a mean terminal half-life of 37 to 45 hours, demonstrating potential for once-daily dosing.
Based on the results of the studies presented at The Liver Meeting, Gilead is advancing its HCV pipeline with three new studies slated for initiation before the end of 2010. The first is a Phase IIb clinical trial of GS 9190 and GS 9256 administered with the current standard of care, evaluating the potential to reduce the required duration of HCV therapy (including RBV/Peg-IFN) from 48 to 16 weeks. Similarly, a second Phase IIb trial will assess GS 9190 plus GS 9451 and the current standard of care. Finally, Gilead will be initiating a drug interaction study of GS 5885 in preparation for a Phase IIb study of GS 5885 plus a protease inhibitor and the current standard of care.
GS 9190, GS 9256, GS 9451 and GS 5885 are investigational products and have not yet been determined safe or efficacious in humans.
About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company's mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North America, Europe and Australia.
Forward-Looking Statement
This press release includes forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995, which are subject to risks, uncertainties and other factors, including the risks related to Gilead's ability to complete Phase II clinical trials of GS 9190 and GS 9256 in a timely matter or at all. There may be unfavorable results in ongoing or any further clinical trials of GS 9190, GS 9256, GS 9451 and GS 5885, and Gilead may need to modify, delay or terminate such clinical trials. Gilead may ultimately be unable to obtain FDA and other regulatory approvals, and as a result, GS 9190 and GS 9256 may never be successfully commercialized. In addition, Gilead may choose to advance alternative candidates in its HCV pipeline based on the emerging profile of these compounds in clinical trials. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead's Quarterly Report on Form 10-Q for the first and second quarters of 2010, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.
For more information on Gilead Sciences, please visit the company's website at http://www.gilead.com/ or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.
(1) National Institutes of Health. Chronic Hepatitis C: Current Disease Management. November 2006.
SOURCE: Gilead Sciences, Inc.
Gilead Sciences, Inc.
Susan Hubbard, 650-522-5715 (Investors)
Cara Miller, 650-522-1616 (Media)
Source
BOSTON, Oct 30, 2010 (BUSINESS WIRE) -- Gilead Sciences, Inc. /quotes/comstock/15*!gild/quotes/nls/gild (GILD 39.67, -0.19, -0.48%) today announced data from a Phase IIa study showing that its investigational compounds GS 9190 and GS 9256, used in conjunction with current standard of care therapies, produced substantial suppression of the hepatitis C virus (HCV) within 28 days of treatment. The findings are being presented Monday, November 1, during a latebreaker oral session (#LB-1) at the 61st annual meeting of the American Association for the Study of Liver Diseases (The Liver Meeting 2010) in Boston.
"Patients with chronic hepatitis C urgently need new and better treatment options, particularly combination therapies involving antiviral drugs that employ multiple mechanisms of action to eradicate the virus," said the study's principal investigator, Stefan Zeuzem, MD, JW Goethe University Hospital, Frankfurt, Germany. "The data presented today support the continued clinical evaluation of GS 9190 and GS 9256 in combination with other hepatitis C therapies and provide additional clinical insight into the effect of ribavirin in the absence of interferon."
More than seven million people in industrialized countries are chronically infected with HCV, and as many as three million Americans have the disease. The current standard of care in HCV therapy is the oral antiviral ribavirin (RBV), administered in combination with peg-interferon (Peg-IFN), which is delivered via injection and achieves a sustained therapeutic response in only 40-55 percent of patients with HCV genotype 1, the most common form of HCV in the Americas and Europe.(1)
Gilead's three-arm Phase IIa trial (Study 196-0112) evaluated the safety and efficacy of GS 9190, an oral polymerase inhibitor, in combination with GS 9256, an oral protease inhibitor, when used as: 1) a dual antiviral therapy alone; 2) a three-drug regimen with RBV; or 3) a four-drug regimen with RBV and Peg-IFN. The study found that the all-oral regimen of GS 9190, GS 9256 and RBV produced substantial viral suppression, with a median maximal decline from baseline in HCV RNA of 5.1 log10 IU/mL during 28 days of treatment. Among patients given the four-drug regimen of GS 9190, GS 9256, RBV and Peg-IFN, 100 percent (14/14 patients) achieved Rapid Virologic Response (RVR) (HCV RNA < 25 IU/mL) at day 28, with 93 percent (13/14 patients) achieving undetectable viral levels (HCV RNA < 10 IU/mL). No virologic breakthroughs were observed in this arm.
"Oral combinations of multiple antiviral agents are expected to become the new standard of care for patients with hepatitis C, and our ultimate goal and vision is to develop a potent and well-tolerated fixed-dose combination product that will eliminate the need for peg-interferon," said John McHutchison, MD, Senior Vice President for Liver Disease Therapeutics at Gilead. "These data strongly support the clinical potential of this oral combination HCV therapy, and we're looking forward to advancing the development of GS 9190 and GS 9256."
About Study 196-0112
This Phase IIa, randomized, open-label trial is evaluating GS 9190 and GS 9256 in combination (n=16), and with RBV (n=15) or with RBV/Peg-IFN (n=15). The trial enrolled treatment-naive adults with chronic HCV genotype 1 for a 28-day course of treatment. The primary outcome measures of the trial are the percentage of subjects achieving RVR, defined as HCV RNA < 25 IU/mL at Day 28, as well as the incidence of treatment-related side effects and adverse events.
Patients in the two-drug arm of the study received GS 9190 (40 mg twice daily) and GS 9256 (75 mg twice daily). Patients in the three-drug arm received a regimen of GS 9190, GS 9256 and RBV (1,000-1,200 mg total daily dose, administered twice daily), and patients in the four-drug arm also received Peg-IFN (180 g, injected once per week). In the final analysis, one patient in the four-drug arm was excluded due to a protocol violation. A median maximal decline from baseline HCV RNA of 4.1 log10 IU/mL was observed in patients receiving the two-drug combination of GS 9190 and GS 9256. The addition of RBV and RBV/Peg-IFN enhanced these responses, with median maximal RNA declines of 5.1 log10 IU/mL and 5.7 log10 IU/mL, respectively.
GS 9190 and GS 9256 were generally well tolerated. The majority of adverse events were Grade 1 or 2 in severity and resolved with continued treatment. The most common adverse events observed in each of the three arms were headache, diarrhea and nausea. Some patients taking the three-drug combination also experienced fatigue and insomnia, and some patients taking the four-drug combination experienced influenza-like illness, fatigue, myalgia and cough. There were two serious adverse events including one case of bursitis and a hospitalization for vasovagal collapse (fainting), which was attributed to gastroenteritis and occurred in a patient who continued therapy and achieved RVR. Elevations in bilirubin were observed across all three study arms, the majority of which were Grade 1 or 2 in severity and none of which resulted in study drug discontinuation.
Additional Gilead HCV Pipeline Research
In addition to Study 196-0112, data from seven additional studies will be presented at The Liver Meeting highlighting the clinical profile of the company's other HCV pipeline candidates, including another protease inhibitor, GS 9451, and a novel NS5A inhibitor, GS 5885. Gilead's HCV pipeline now includes seven unique molecules spanning six therapeutic classes with different mechanisms of action. Five of these compounds are currently in clinical trials, and two are slated to enter human clinical studies early next year.
In a Phase I three-day dose-ranging study (Study 169-0103), GS 9451 was found to be highly potent in terms of anti-HCV activity and demonstrated a long plasma half-life with once-daily dosing potential (Abstract #820). GS 9451 was tested among 33 patients with HCV genotype 1a (GT1a) or 1b (GT1b). GT1a patients received GS 9451 at 60 mg, 200 mg and 400 mg once-daily doses, and the median maximal decline from baseline in HCV RNA was 0.88, 3.2 and 3.6 log10 IU/mL, respectively. GT1b patients received GS 9451 at a 200 mg once-daily dose, and the median maximal reduction was 3.5 log10 IU/mL. The median half-life of GS 9451 at these doses ranged from 14 to 17 hours, which will allow for once-daily dosing. Treatment-emergent adverse events were generally mild to moderate. Adverse events occurring in at least two patients at any dose were headache (n=7) and dyspepsia (n=2).
Gilead also presented the first Phase I data on a novel NS5A inhibitor for HCV (Study 256-0101), GS 5885, which suggest that this compound also has once-daily dosing potential (Abstract #1883). In preclinical studies, GS 5885 demonstrated low picomolar potency and a favorable safety and pharmacokinetic profile. The clinical safety profile of GS 5885 was assessed in an escalating, single oral dose trial in 54 healthy volunteers (randomized 8:2 to receive GS 5885 versus placebo). The compound was dosed under fasted conditions at 3 mg, 10 mg, 30 mg (under fasted and fed conditions), 60 mg and 100 mg, and was well tolerated, with no serious adverse events and no treatment-emergent grade 3/4 laboratory abnormalities for one week after a single dose. Adverse events were few and generally mild, and included headache, dizziness, myalgia, dysmenorrhea and contact dermatitis from electrocardiogram (ECG) leads. GS 5885 exposure was proportional over the dosing range and produced a mean terminal half-life of 37 to 45 hours, demonstrating potential for once-daily dosing.
Based on the results of the studies presented at The Liver Meeting, Gilead is advancing its HCV pipeline with three new studies slated for initiation before the end of 2010. The first is a Phase IIb clinical trial of GS 9190 and GS 9256 administered with the current standard of care, evaluating the potential to reduce the required duration of HCV therapy (including RBV/Peg-IFN) from 48 to 16 weeks. Similarly, a second Phase IIb trial will assess GS 9190 plus GS 9451 and the current standard of care. Finally, Gilead will be initiating a drug interaction study of GS 5885 in preparation for a Phase IIb study of GS 5885 plus a protease inhibitor and the current standard of care.
GS 9190, GS 9256, GS 9451 and GS 5885 are investigational products and have not yet been determined safe or efficacious in humans.
About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company's mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North America, Europe and Australia.
Forward-Looking Statement
This press release includes forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995, which are subject to risks, uncertainties and other factors, including the risks related to Gilead's ability to complete Phase II clinical trials of GS 9190 and GS 9256 in a timely matter or at all. There may be unfavorable results in ongoing or any further clinical trials of GS 9190, GS 9256, GS 9451 and GS 5885, and Gilead may need to modify, delay or terminate such clinical trials. Gilead may ultimately be unable to obtain FDA and other regulatory approvals, and as a result, GS 9190 and GS 9256 may never be successfully commercialized. In addition, Gilead may choose to advance alternative candidates in its HCV pipeline based on the emerging profile of these compounds in clinical trials. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead's Quarterly Report on Form 10-Q for the first and second quarters of 2010, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.
For more information on Gilead Sciences, please visit the company's website at http://www.gilead.com/ or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.
(1) National Institutes of Health. Chronic Hepatitis C: Current Disease Management. November 2006.
SOURCE: Gilead Sciences, Inc.
Gilead Sciences, Inc.
Susan Hubbard, 650-522-5715 (Investors)
Cara Miller, 650-522-1616 (Media)
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Viread(R) for Hepatitis B Maintains Antiviral Suppression with No Development of Resistance Through Four Years of Treatment
-- New Long-Term Data Also Show Significant "s" Antigen Loss in Key Patient Population --
BOSTON, Oct 30, 2010 (BUSINESS WIRE) -- Gilead Sciences, Inc. /quotes/comstock/15*!gild/quotes/nls/gild (GILD 39.67, -0.19, -0.48%) today announced new data from the open-label phase of two pivotal Phase III clinical trials (Studies 102 and 103) evaluating the four-year efficacy of Viread(R) (tenofovir disoproxil fumarate) for the treatment of chronic hepatitis B virus (HBV) infection. Significantly, no resistance to Viread emerged over 192 weeks of treatment, and 10.8 percent of patients receiving Viread in Study 103 (HBeAg-positive) for four years experienced surface, or "s", antigen (HBsAg) loss, which is a marker of the resolution of chronic HBV infection. Additional data from these studies and from Study 106 show the durable antiviral efficacy of Viread among several key patient subpopulations, including patients with high baseline viral levels, individuals of Asian descent and treatment-experienced patients. These findings are being presented at the 61st annual meeting of the American Association for the Study of Liver Diseases (The Liver Meeting 2010) in Boston.
"The complete absence of Viread-related resistance detected among study participants shows that this therapy has a high and durable barrier to viral resistance, which is essential for the long-term success of HBV therapy," said Patrick Marcellin, MD, of Hopital Beaujon in Clichy, France, INSERM CRB3 and University of Paris Denis Diderot, and the principal investigator of Study 102. "These four-year results underscore the long-term benefits of Viread for diverse patient populations, including those who are difficult to treat."
The 192-week data from Studies 102 and 103 evaluate the intent-to-treat population (with the exception of those who left the study for administrative reasons). In Studies 102 and 103, the majority of patients who received Viread for up to 192 weeks experienced sustained suppression of HBV DNA levels in the blood below 400 copies/mL and normalization of alanine aminotransferase (ALT, an enzyme that serves as a measure of liver damage). Notably, no HBV pol/RT amino acid substitutions associated with tenofovir resistance were detected through 192 weeks of Viread.
Among HBeAg-positive patients, 29 percent (based on observed data at week 192) experienced "e" antigen seroconversion, which is defined as both the disappearance of the hepatitis B "e" antigen, a marker of HBV replication (rendering the patient "HBe-antigen negative"), and the appearance of antibodies to this antigen (making the patient "HBe-antibody positive"). Additionally, among HBeAg-positive patients receiving Viread through 192 weeks, the cumulative probability (estimated by Kaplan-Meier) of "s" antigen loss, suggesting that HBV infections may have cleared completely, was 10.8 percent.
"Over the years, physicians have come to understand the critical role of 's' antigen loss in the cessation of disease activity," said Jenny Heathcote, MD, of the University of Toronto, Canada, and the principal investigator for Study 103. "The 10.8 percent 's' loss observed in this trial is a significant finding that makes Viread a highly attractive treatment option for HBV."
Viread for HBV was approved by the U.S. Food and Drug Administration (FDA) in 2008 and has since become the most-prescribed HBV medicine in the United States. It is the only recommended first-line therapy for hepatitis B to demonstrate continuous efficacy and safety through four years in pivotal studies. In October 2010, the FDA expanded Viread's indication to include the treatment of chronic hepatitis B among patients with decompensated liver disease, the end stage of hepatitis B in which liver function is marginal and clinical complications frequently occur. Decompensated liver disease is an indication for consideration of liver transplantation.
Viread Data at The Liver Meeting
Studies 102 and 103 are both multi-center, randomized, double-blind Phase III clinical trials comparing Viread to Hepsera(R) (adefovir dipivoxil) among HBeAg-negative presumed pre-core mutant (Study 102; n=375) and HBeAg-positive (Study 103; n=266) chronic hepatitis B patients with compensated liver disease. Patients had HBV DNA (viral load) above 100,000 copies/mL and elevated levels of ALT upon study initiation. The majority of patients were treatment-naive, although some patients had prior lamivudine treatment experience. Patients originally randomized to Hepsera in both studies rolled over to open-label Viread treatment (n=196) at week 48, while patients originally randomized to Viread continued open-label Viread (n=389). After 72 weeks, patients with confirmed viremia (HBV DNA levels at or above 400 copies/mL on two consecutive visits) had the option of adding emtricitabine treatment by substituting Truvada(R) (emtricitabine and tenofovir disoproxil fumarate) for Viread. The number of patients entering year four was 218 (Study 102) and 130 (Study 103) for those originally randomized to receive Viread and 109 (Study 102) and 71 (Study 103) for those originally randomized to receive Hepsera.
Overall Efficacy and Safety at Week 192 (Abstracts 476 and 477)
In an on-treatment analysis, 99 percent of patients in Study 102 and 96 percent of patients in Study 103 who were originally randomized to receive Viread through 192 weeks achieved viral suppression below 400 copies/mL. Among those who were originally randomized to receive Hepsera, 100 percent of patients in Study 102 and 99 percent of patients in Study 103 achieved viral suppression below 400 copies/mL. In an analysis in which the addition of emtricitabine equals failure, 84 percent and 68 percent of patients (Studies 102 and 103, respectively) originally randomized to receive Viread and 87 percent and 72 percent of patients (Studies 102 and 103, respectively) originally randomized to receive Hepsera experienced sustained viral suppression. The majority of patients with elevated ALT at baseline achieved normalized ALT on treatment (ranging from 77 percent to 86 percent across both arms in both studies). Viread was well-tolerated in both studies. During the open-label period (week 48 through week 192), seven patients discontinued treatment due to an adverse event. Creatinine levels, an indicator of kidney function, remained stable through 192 weeks.
Patients with High Viral Load (Abstract 137)
In a subgroup analysis pooling data from Studies 102 and 103, 71 percent of patients who entered the trials with high viral levels (HBV DNA of at least 9 log10 copies/mL) (n=129), achieved sustained viral suppression after 192 weeks of Viread treatment. Of 29 patients who opted to add emtricitabine treatment after 72 weeks due to confirmed viremia, 20 had viral suppression at week 192. At week 192, ALT levels were normalized in 77 percent of patients with high viral load at baseline. Among HBeAg-positive patients (n=118) in this group, 35 percent achieved HBeAg loss and 23 percent experienced HBeAg seroconversion. Overall, 15 percent of patients with high viral load experienced HBsAg loss.
Patients of Asian Descent (Abstract 481)
In another subgroup analysis pooling four-year data from Studies 102 and 103, 77 percent of Asian patients achieved sustained viral suppression (163 patients entered the open-label study phase). Of seven Asian patients who added emtricitabine treatment during the study, four of six remaining on study had viral suppression at week 192. ALT levels normalized in 86 percent of Asians after 192 weeks on treatment. Of 65 HBeAg-positive Asian patients with week 192 serology results, 35 percent achieved HBeAg loss and 26 percent experienced HBeAg seroconversion. Viread was well tolerated among this group of patients. During the open-label phase of Viread treatment, serious adverse events occurred in 6 percent of Asian patients, while grade 3-4 laboratory abnormalities occurred in 15 percent. During the study, one Asian patient had a confirmed serum phosphorus level less than 2 mg/dL, which normalized by week 192, and another had a confirmed increase of at least 0.5 mg/dL in serum creatinine.
Treatment-Experienced Patients (Abstract 136)
In Study 106, Viread showed sustained efficacy in patients with prior Hepseratreatment experience through 168 weeks. Patients with an incomplete virologic response after receiving Hepsera for at least six months were randomly assigned to Viread (n=53) or Truvada (n=52). More than half of all patients also had prior treatment experience with lamivudine. Sixteen patients in the Viread arm and nine patients in the Truvada arm remained viremic (HBV DNA greater than 400 copies/mL) after week 24 and initiated open-label Truvada.
The percent of patients achieving viral suppression (HBV DNA below 400 copies/mL) through 168 weeks was the same in both arms of the study at 82 percent. Additionally, 100 percent of patients with baseline resistance mutations to lamivudine (13/13 patients) and 90 percent of patients with baseline resistance mutations to adefovir (9/10 patients) achieved viral suppression. ALT normalization occurred in 68 percent of Viread and 67 percent of Truvada patients. Both Viread and Truvada were well tolerated, and no unexpected or clinically important adverse events related to renal function were reported among these treatment-experienced patients. Notably, no patient experienced a confirmed increase of at least 0.5 mg/dL in serum creatinine, calculated creatinine clearance less than 50 mL/min or serum phosphorus less than 2.0 mg/dL.
Important Information About Viread for Chronic Hepatitis B
Viread (tenofovir disoproxil fumarate) is indicated for the treatment of chronic hepatitis B in adults. This indication is based primarily on data from the treatment of nucleoside-treatment-naive patients, and a smaller number of patients who had previously received lamivudine or adefovir. Patients were adults with HBeAg-positive and HBeAg-negative chronic hepatitis B with compensated liver disease. Viread was evaluated in a limited number of subjects with chronic hepatitis B and decompensated liver disease. The number of patients in clinical trials who had lamivudine- or adefovir-associated substitutions at baseline was too small to reach conclusions of efficacy.
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleos(t)ide analogs, including Viread, in combination with other antiretrovirals.
Severe acute exacerbations of hepatitis have been reported in HBV-infected patients who have discontinued anti-hepatitis B therapy, including Viread. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-hepatitis B therapy, including Viread. If appropriate, resumption of anti-hepatitis B therapy may be warranted.
New onset or worsening of renal impairment including cases of acute renal failure and Fanconi syndrome has been reported with the use of Viread. It is recommended to assess creatinine clearance (CrCl) before initiating treatment with Viread and monitor CrCl and serum phosphorus in patients at risk, including those who have previously experienced renal events while receiving Hepsera. Administering Viread with concurrent or recent use of nephrotoxic drugs should be avoided.
Viread should not be used with other tenofovir-containing products (e.g. Atripla, Truvada). Viread should not be administered in combination with Hepsera.
Due to the risk of development of HIV-1 resistance, Viread should only be used as part of an appropriate antiretroviral combination regimen in HIV-infected patients with or without HBV coinfection. HIV antibody testing should be offered to all HBV-infected patients before initiating therapy with Viread.
Decreases in bone mineral density (BMD) have been observed in HIV-infected patients. It is recommended that BMD monitoring be considered for patients with a history of pathologic fracture or who are at risk for osteopenia. The bone effects of Viread have not been studied in patients with chronic HBV infection. Cases of osteomalacia (associated with proximal renal tubulopathy and which may contribute to fractures) have been reported in association with the use of Viread.
Coadministration of Viread with didanosine increases didanosine concentrations. Use with caution and monitor for evidence of didanosine toxicity (eg, pancreatitis, neuropathy). Didanosine should be discontinued in patients who develop didanosine-associated adverse reactions. In adults weighing >60 kg, the didanosine dose should be reduced to 250 mg when it is coadministered with Viread. Data are not available to recommend a dose adjustment of didanosine for patients weighing <60 kg Coadministration of Viread with atazanavir decreases atazanavir concentrations and increases tenofovir concentrations. Use atazanavir with Viread only with additional ritonavir; monitor for evidence of tenofovir toxicity. Coadministration of Viread with lopinavir/ritonavir increases tenofovir concentrations. Monitor for evidence of tenofovir toxicity.
In controlled clinical trials in patients with chronic hepatitis B with compensated liver disease, the most common adverse reaction (all grades) was nausea, observed in 9 percent of patients taking Viread at week 48. Other adverse reactions observed at week 48 in greater than 5 percent of patients treated with Viread include abdominal pain, diarrhea, headache, dizziness, fatigue, nasopharyngitis, back pain and skin rash.
In HBV-infected patients with decompensated liver disease, the most common adverse reactions (all grades) reported in greater-than or equal to 10 percent of patients treated with Viread were abdominal pain (22 percent), nausea (20 percent), insomnia (18 percent), pruritus (16 percent), vomiting (13 percent), dizziness (13 percent), and pyrexia (11 percent).
The recommended dose for the treatment of chronic hepatitis B is 300 mg once daily taken orally without regard to food. The dosing interval of Viread should be adjusted and renal function closely monitored in patients with moderate and severe renal impairment.
The parent compound of Viread was discovered through a collaborative research effort between Dr. Antonin Holy, Institute for Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic (IOCB) in Prague and Dr. Erik DeClercq, Rega Institute for Medical Research, Katholic University in Leuven, Belgium. The inventors of Viread have agreed to waive their right to a royalty on sales of Viread and Truvada in Gilead Access Program countries to ensure the product can be offered at a no-profit price in parts of the world where the HIV/AIDS epidemic has hit the hardest.
Important Information about Hepsera (adefovir dipivoxil)
Hepsera (adefovir dipivoxil) is indicated for the treatment of chronic hepatitis B in patients 12 years of age and older with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease. This indication is based on histological, virological, biochemical and serological responses in adult patients with HBeAg-positive and HBeAg-negative chronic hepatitis B with compensated liver function, and with clinical evidence of lamivudine-resistant hepatitis B virus with either compensated or decompensated liver function.
For patients 12 to less than 18 years of age, the indication is based on virological and biochemical responses in patients with HBeAg-positive chronic hepatitis B virus infection with compensated liver function.
Severe acute exacerbations of hepatitis have been reported in patients who have discontinued anti-hepatitis B therapy, including Hepsera. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-hepatitis B therapy. If appropriate, resumption of anti-hepatitis B therapy may be warranted.
In patients at risk of or having underlying renal dysfunction, chronic administration of Hepsera may result in nephrotoxicity. These patients should be monitored closely for renal function and may require dose adjustment. It is important to monitor renal function for all patients during treatment with Hepsera, particularly for those with pre-existing or other risks for renal impairment and patients taking concomitant nephrotoxic agents. Patients with renal insufficiency at baseline or during treatment may require dose adjustment. Caution should be exercised when prescribing Hepsera to adolescents with underlying renal dysfunction, and renal function in these patients should be closely monitored.
HIV resistance may emerge in chronic hepatitis B patients with unrecognized or untreated HIV infection treated with anti-hepatitis B therapies, such as therapy with Hepsera, which may have activity against HIV. HIV antibody testing should be offered to all HBV-infected patients before initiating therapy with Hepsera.
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleos(t)ide analogs alone or in combination with other antiretrovirals.
Resistance to adefovir dipivoxil can result in viral load rebound which may result in exacerbation of hepatitis and, in the setting of diminished hepatic function, lead to liver decompensation and possible fatal outcomes. To reduce the risk of resistance in patients with lamivudine resistant HBV, adefovir dipivoxil should be used in combination with lamivudine and not as adefovir dipivoxil monotherapy. To reduce the risk of resistance in all patients receiving adefovir dipivoxil monotherapy, a modification of treatment should be considered if serum HBV DNA remains above 1000 copies/mL with continued treatment.
The most common adverse reaction (less than 10 percent) in compensated disease patients is asthenia and in pre- and post-transplantation lamivudine-resistant liver disease patients is increased creatinine.
The recommended dose for the treatment of chronic hepatitis B is 10 mg once daily taken orally without regard to food. The dosing interval of Hepsera should be adjusted in patients with renal impairment.
Important Information About Truvada
Truvada is a fixed-dose combination tablet containing 200 mg of emtricitabine (Emtriva(R)) and 300 mg of tenofovir disoproxil fumarate (Viread). In the United States, Truvada is indicated in combination with other antiretroviral agents (such as non-nucleoside reverse transcriptase inhibitors or protease inhibitors) for the treatment of HIV-1 infection in adults.
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleos(t)ide analogs, including Viread, a component of Truvada.
Truvada is not approved for the treatment of chronic hepatitis B virus (HBV) infection. Severe acute exacerbations of hepatitis B have been reported in patients coinfected with HIV-1 and HBV who have discontinued Truvada. Hepatic function should be monitored closely in these patients. If appropriate, initiation of anti-hepatitis B therapy may be warranted.
Truvada should not be coadministered with Atripla, Emtriva, Viread or lamivudine-containing products, including Combivir(R) (lamivudine/zidovudine), Epivir(R) or Epivir-HBV(R) (lamivudine), Epzicom(R) (abacavir sulfate/lamivudine) or Trizivir(R) (abacavir sulfate/lamivudine/zidovudine). In treatment-experienced patients, the use of Truvada should be guided by laboratory testing and treatment history.
Emtricitabine and tenofovir are principally eliminated by the kidneys. Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been reported in association with the use of Viread. It is recommended that creatinine clearance be calculated in all patients prior to initiating therapy with Truvada and as clinically appropriate during therapy.
Routine monitoring of calculated creatinine clearance and serum phosphorous should be performed in patients at risk for renal impairment including patients who have previously experienced renal events while receiving Hepsera(R) (adefovir dipivoxil).
Dosing interval adjustment and close monitoring of renal function are recommended in all patients with creatinine clearance 30-49 ml/min. Truvada should be avoided with concurrent or recent use of a nephrotoxic agent. Truvada should not be administered with Hepsera.
Coadministration of Truvada and didanosine should be undertaken with caution. Patients should be monitored closely for didanosine-associated adverse events and didanosine should be discontinued if these occur. Dose reduction of didanosine should be considered, if warranted. Patients on atazanavir and lopinavir/ritonavir plus Truvada should be monitored for Truvada-associated adverse events and Truvada should be discontinued if these occur. When co-administered with Truvada, it is recommended that atazanavir be boosted with ritonavir 100 mg. Atazanavir without ritonavir should not be co-administered with Truvada.
Decreases in bone mineral density (BMD) at the lumbar spine and hip have been seen with the use of Viread. The effect on long-term bone health and future fracture risk is unknown. BMD monitoring should be considered in patients with a history of pathologic fractures or who are at risk for osteopenia. Cases of osteomalacia (associated with proximal renal tubulopathy and which may contribute to fractures) have been reported in association with the use of Viread.
Changes in body fat have been observed in patients taking anti-HIV medicines. Immune Reconstitution Syndrome has been reported in patients treated with combination therapy, including Viread and Emtriva, and may necessitate further evaluation and treatment.
The most common adverse reactions (incidence greater-than or equal to 10 percent) are diarrhea, nausea, fatigue, headache, dizziness, depression, insomnia, abnormal dreams and rash.
About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company's mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North America, Europe and Australia.
Forward-Looking Statement
This press release includes forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995, that are subject to risks, uncertainties and other factors, including the risks that physicians may not prescribe Viread over other existing or future HBV medications. In addition, as Viread is used over longer periods of time by many patients with underlying health problems, taking numerous other medicines, safety, resistance, drug interaction or other issues may arise, which could reduce the market acceptance of Viread. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead's 2009 Annual report on Form 10-K and in Quarterly Reports on Form 10-Q for the first and second quarters of 2010, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.
U.S. full prescribing information for Viread is available at http://www.viread.com/. U.S. full prescribing information for Truvada is available at http://www.truvada.com/. U.S. full prescribing information for Hepsera is available at www.Hepsera.com.
Viread, Truvada and Hepsera are registered trademarks of Gilead Sciences, Inc.
For more information on Gilead Sciences, please visit the company's website at http://www.gilead.com/ or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.
SOURCE: Gilead Sciences, Inc.
Gilead Sciences, Inc.
Patrick O'Brien, 650-522-1936
Investors
or
Cara Miller, 650-522-1616
Media
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BOSTON, Oct 30, 2010 (BUSINESS WIRE) -- Gilead Sciences, Inc. /quotes/comstock/15*!gild/quotes/nls/gild (GILD 39.67, -0.19, -0.48%) today announced new data from the open-label phase of two pivotal Phase III clinical trials (Studies 102 and 103) evaluating the four-year efficacy of Viread(R) (tenofovir disoproxil fumarate) for the treatment of chronic hepatitis B virus (HBV) infection. Significantly, no resistance to Viread emerged over 192 weeks of treatment, and 10.8 percent of patients receiving Viread in Study 103 (HBeAg-positive) for four years experienced surface, or "s", antigen (HBsAg) loss, which is a marker of the resolution of chronic HBV infection. Additional data from these studies and from Study 106 show the durable antiviral efficacy of Viread among several key patient subpopulations, including patients with high baseline viral levels, individuals of Asian descent and treatment-experienced patients. These findings are being presented at the 61st annual meeting of the American Association for the Study of Liver Diseases (The Liver Meeting 2010) in Boston.
"The complete absence of Viread-related resistance detected among study participants shows that this therapy has a high and durable barrier to viral resistance, which is essential for the long-term success of HBV therapy," said Patrick Marcellin, MD, of Hopital Beaujon in Clichy, France, INSERM CRB3 and University of Paris Denis Diderot, and the principal investigator of Study 102. "These four-year results underscore the long-term benefits of Viread for diverse patient populations, including those who are difficult to treat."
The 192-week data from Studies 102 and 103 evaluate the intent-to-treat population (with the exception of those who left the study for administrative reasons). In Studies 102 and 103, the majority of patients who received Viread for up to 192 weeks experienced sustained suppression of HBV DNA levels in the blood below 400 copies/mL and normalization of alanine aminotransferase (ALT, an enzyme that serves as a measure of liver damage). Notably, no HBV pol/RT amino acid substitutions associated with tenofovir resistance were detected through 192 weeks of Viread.
Among HBeAg-positive patients, 29 percent (based on observed data at week 192) experienced "e" antigen seroconversion, which is defined as both the disappearance of the hepatitis B "e" antigen, a marker of HBV replication (rendering the patient "HBe-antigen negative"), and the appearance of antibodies to this antigen (making the patient "HBe-antibody positive"). Additionally, among HBeAg-positive patients receiving Viread through 192 weeks, the cumulative probability (estimated by Kaplan-Meier) of "s" antigen loss, suggesting that HBV infections may have cleared completely, was 10.8 percent.
"Over the years, physicians have come to understand the critical role of 's' antigen loss in the cessation of disease activity," said Jenny Heathcote, MD, of the University of Toronto, Canada, and the principal investigator for Study 103. "The 10.8 percent 's' loss observed in this trial is a significant finding that makes Viread a highly attractive treatment option for HBV."
Viread for HBV was approved by the U.S. Food and Drug Administration (FDA) in 2008 and has since become the most-prescribed HBV medicine in the United States. It is the only recommended first-line therapy for hepatitis B to demonstrate continuous efficacy and safety through four years in pivotal studies. In October 2010, the FDA expanded Viread's indication to include the treatment of chronic hepatitis B among patients with decompensated liver disease, the end stage of hepatitis B in which liver function is marginal and clinical complications frequently occur. Decompensated liver disease is an indication for consideration of liver transplantation.
Viread Data at The Liver Meeting
Studies 102 and 103 are both multi-center, randomized, double-blind Phase III clinical trials comparing Viread to Hepsera(R) (adefovir dipivoxil) among HBeAg-negative presumed pre-core mutant (Study 102; n=375) and HBeAg-positive (Study 103; n=266) chronic hepatitis B patients with compensated liver disease. Patients had HBV DNA (viral load) above 100,000 copies/mL and elevated levels of ALT upon study initiation. The majority of patients were treatment-naive, although some patients had prior lamivudine treatment experience. Patients originally randomized to Hepsera in both studies rolled over to open-label Viread treatment (n=196) at week 48, while patients originally randomized to Viread continued open-label Viread (n=389). After 72 weeks, patients with confirmed viremia (HBV DNA levels at or above 400 copies/mL on two consecutive visits) had the option of adding emtricitabine treatment by substituting Truvada(R) (emtricitabine and tenofovir disoproxil fumarate) for Viread. The number of patients entering year four was 218 (Study 102) and 130 (Study 103) for those originally randomized to receive Viread and 109 (Study 102) and 71 (Study 103) for those originally randomized to receive Hepsera.
Overall Efficacy and Safety at Week 192 (Abstracts 476 and 477)
In an on-treatment analysis, 99 percent of patients in Study 102 and 96 percent of patients in Study 103 who were originally randomized to receive Viread through 192 weeks achieved viral suppression below 400 copies/mL. Among those who were originally randomized to receive Hepsera, 100 percent of patients in Study 102 and 99 percent of patients in Study 103 achieved viral suppression below 400 copies/mL. In an analysis in which the addition of emtricitabine equals failure, 84 percent and 68 percent of patients (Studies 102 and 103, respectively) originally randomized to receive Viread and 87 percent and 72 percent of patients (Studies 102 and 103, respectively) originally randomized to receive Hepsera experienced sustained viral suppression. The majority of patients with elevated ALT at baseline achieved normalized ALT on treatment (ranging from 77 percent to 86 percent across both arms in both studies). Viread was well-tolerated in both studies. During the open-label period (week 48 through week 192), seven patients discontinued treatment due to an adverse event. Creatinine levels, an indicator of kidney function, remained stable through 192 weeks.
Patients with High Viral Load (Abstract 137)
In a subgroup analysis pooling data from Studies 102 and 103, 71 percent of patients who entered the trials with high viral levels (HBV DNA of at least 9 log10 copies/mL) (n=129), achieved sustained viral suppression after 192 weeks of Viread treatment. Of 29 patients who opted to add emtricitabine treatment after 72 weeks due to confirmed viremia, 20 had viral suppression at week 192. At week 192, ALT levels were normalized in 77 percent of patients with high viral load at baseline. Among HBeAg-positive patients (n=118) in this group, 35 percent achieved HBeAg loss and 23 percent experienced HBeAg seroconversion. Overall, 15 percent of patients with high viral load experienced HBsAg loss.
Patients of Asian Descent (Abstract 481)
In another subgroup analysis pooling four-year data from Studies 102 and 103, 77 percent of Asian patients achieved sustained viral suppression (163 patients entered the open-label study phase). Of seven Asian patients who added emtricitabine treatment during the study, four of six remaining on study had viral suppression at week 192. ALT levels normalized in 86 percent of Asians after 192 weeks on treatment. Of 65 HBeAg-positive Asian patients with week 192 serology results, 35 percent achieved HBeAg loss and 26 percent experienced HBeAg seroconversion. Viread was well tolerated among this group of patients. During the open-label phase of Viread treatment, serious adverse events occurred in 6 percent of Asian patients, while grade 3-4 laboratory abnormalities occurred in 15 percent. During the study, one Asian patient had a confirmed serum phosphorus level less than 2 mg/dL, which normalized by week 192, and another had a confirmed increase of at least 0.5 mg/dL in serum creatinine.
Treatment-Experienced Patients (Abstract 136)
In Study 106, Viread showed sustained efficacy in patients with prior Hepseratreatment experience through 168 weeks. Patients with an incomplete virologic response after receiving Hepsera for at least six months were randomly assigned to Viread (n=53) or Truvada (n=52). More than half of all patients also had prior treatment experience with lamivudine. Sixteen patients in the Viread arm and nine patients in the Truvada arm remained viremic (HBV DNA greater than 400 copies/mL) after week 24 and initiated open-label Truvada.
The percent of patients achieving viral suppression (HBV DNA below 400 copies/mL) through 168 weeks was the same in both arms of the study at 82 percent. Additionally, 100 percent of patients with baseline resistance mutations to lamivudine (13/13 patients) and 90 percent of patients with baseline resistance mutations to adefovir (9/10 patients) achieved viral suppression. ALT normalization occurred in 68 percent of Viread and 67 percent of Truvada patients. Both Viread and Truvada were well tolerated, and no unexpected or clinically important adverse events related to renal function were reported among these treatment-experienced patients. Notably, no patient experienced a confirmed increase of at least 0.5 mg/dL in serum creatinine, calculated creatinine clearance less than 50 mL/min or serum phosphorus less than 2.0 mg/dL.
Important Information About Viread for Chronic Hepatitis B
Viread (tenofovir disoproxil fumarate) is indicated for the treatment of chronic hepatitis B in adults. This indication is based primarily on data from the treatment of nucleoside-treatment-naive patients, and a smaller number of patients who had previously received lamivudine or adefovir. Patients were adults with HBeAg-positive and HBeAg-negative chronic hepatitis B with compensated liver disease. Viread was evaluated in a limited number of subjects with chronic hepatitis B and decompensated liver disease. The number of patients in clinical trials who had lamivudine- or adefovir-associated substitutions at baseline was too small to reach conclusions of efficacy.
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleos(t)ide analogs, including Viread, in combination with other antiretrovirals.
Severe acute exacerbations of hepatitis have been reported in HBV-infected patients who have discontinued anti-hepatitis B therapy, including Viread. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-hepatitis B therapy, including Viread. If appropriate, resumption of anti-hepatitis B therapy may be warranted.
New onset or worsening of renal impairment including cases of acute renal failure and Fanconi syndrome has been reported with the use of Viread. It is recommended to assess creatinine clearance (CrCl) before initiating treatment with Viread and monitor CrCl and serum phosphorus in patients at risk, including those who have previously experienced renal events while receiving Hepsera. Administering Viread with concurrent or recent use of nephrotoxic drugs should be avoided.
Viread should not be used with other tenofovir-containing products (e.g. Atripla, Truvada). Viread should not be administered in combination with Hepsera.
Due to the risk of development of HIV-1 resistance, Viread should only be used as part of an appropriate antiretroviral combination regimen in HIV-infected patients with or without HBV coinfection. HIV antibody testing should be offered to all HBV-infected patients before initiating therapy with Viread.
Decreases in bone mineral density (BMD) have been observed in HIV-infected patients. It is recommended that BMD monitoring be considered for patients with a history of pathologic fracture or who are at risk for osteopenia. The bone effects of Viread have not been studied in patients with chronic HBV infection. Cases of osteomalacia (associated with proximal renal tubulopathy and which may contribute to fractures) have been reported in association with the use of Viread.
Coadministration of Viread with didanosine increases didanosine concentrations. Use with caution and monitor for evidence of didanosine toxicity (eg, pancreatitis, neuropathy). Didanosine should be discontinued in patients who develop didanosine-associated adverse reactions. In adults weighing >60 kg, the didanosine dose should be reduced to 250 mg when it is coadministered with Viread. Data are not available to recommend a dose adjustment of didanosine for patients weighing <60 kg Coadministration of Viread with atazanavir decreases atazanavir concentrations and increases tenofovir concentrations. Use atazanavir with Viread only with additional ritonavir; monitor for evidence of tenofovir toxicity. Coadministration of Viread with lopinavir/ritonavir increases tenofovir concentrations. Monitor for evidence of tenofovir toxicity.
In controlled clinical trials in patients with chronic hepatitis B with compensated liver disease, the most common adverse reaction (all grades) was nausea, observed in 9 percent of patients taking Viread at week 48. Other adverse reactions observed at week 48 in greater than 5 percent of patients treated with Viread include abdominal pain, diarrhea, headache, dizziness, fatigue, nasopharyngitis, back pain and skin rash.
In HBV-infected patients with decompensated liver disease, the most common adverse reactions (all grades) reported in greater-than or equal to 10 percent of patients treated with Viread were abdominal pain (22 percent), nausea (20 percent), insomnia (18 percent), pruritus (16 percent), vomiting (13 percent), dizziness (13 percent), and pyrexia (11 percent).
The recommended dose for the treatment of chronic hepatitis B is 300 mg once daily taken orally without regard to food. The dosing interval of Viread should be adjusted and renal function closely monitored in patients with moderate and severe renal impairment.
The parent compound of Viread was discovered through a collaborative research effort between Dr. Antonin Holy, Institute for Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic (IOCB) in Prague and Dr. Erik DeClercq, Rega Institute for Medical Research, Katholic University in Leuven, Belgium. The inventors of Viread have agreed to waive their right to a royalty on sales of Viread and Truvada in Gilead Access Program countries to ensure the product can be offered at a no-profit price in parts of the world where the HIV/AIDS epidemic has hit the hardest.
Important Information about Hepsera (adefovir dipivoxil)
Hepsera (adefovir dipivoxil) is indicated for the treatment of chronic hepatitis B in patients 12 years of age and older with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease. This indication is based on histological, virological, biochemical and serological responses in adult patients with HBeAg-positive and HBeAg-negative chronic hepatitis B with compensated liver function, and with clinical evidence of lamivudine-resistant hepatitis B virus with either compensated or decompensated liver function.
For patients 12 to less than 18 years of age, the indication is based on virological and biochemical responses in patients with HBeAg-positive chronic hepatitis B virus infection with compensated liver function.
Severe acute exacerbations of hepatitis have been reported in patients who have discontinued anti-hepatitis B therapy, including Hepsera. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-hepatitis B therapy. If appropriate, resumption of anti-hepatitis B therapy may be warranted.
In patients at risk of or having underlying renal dysfunction, chronic administration of Hepsera may result in nephrotoxicity. These patients should be monitored closely for renal function and may require dose adjustment. It is important to monitor renal function for all patients during treatment with Hepsera, particularly for those with pre-existing or other risks for renal impairment and patients taking concomitant nephrotoxic agents. Patients with renal insufficiency at baseline or during treatment may require dose adjustment. Caution should be exercised when prescribing Hepsera to adolescents with underlying renal dysfunction, and renal function in these patients should be closely monitored.
HIV resistance may emerge in chronic hepatitis B patients with unrecognized or untreated HIV infection treated with anti-hepatitis B therapies, such as therapy with Hepsera, which may have activity against HIV. HIV antibody testing should be offered to all HBV-infected patients before initiating therapy with Hepsera.
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleos(t)ide analogs alone or in combination with other antiretrovirals.
Resistance to adefovir dipivoxil can result in viral load rebound which may result in exacerbation of hepatitis and, in the setting of diminished hepatic function, lead to liver decompensation and possible fatal outcomes. To reduce the risk of resistance in patients with lamivudine resistant HBV, adefovir dipivoxil should be used in combination with lamivudine and not as adefovir dipivoxil monotherapy. To reduce the risk of resistance in all patients receiving adefovir dipivoxil monotherapy, a modification of treatment should be considered if serum HBV DNA remains above 1000 copies/mL with continued treatment.
The most common adverse reaction (less than 10 percent) in compensated disease patients is asthenia and in pre- and post-transplantation lamivudine-resistant liver disease patients is increased creatinine.
The recommended dose for the treatment of chronic hepatitis B is 10 mg once daily taken orally without regard to food. The dosing interval of Hepsera should be adjusted in patients with renal impairment.
Important Information About Truvada
Truvada is a fixed-dose combination tablet containing 200 mg of emtricitabine (Emtriva(R)) and 300 mg of tenofovir disoproxil fumarate (Viread). In the United States, Truvada is indicated in combination with other antiretroviral agents (such as non-nucleoside reverse transcriptase inhibitors or protease inhibitors) for the treatment of HIV-1 infection in adults.
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleos(t)ide analogs, including Viread, a component of Truvada.
Truvada is not approved for the treatment of chronic hepatitis B virus (HBV) infection. Severe acute exacerbations of hepatitis B have been reported in patients coinfected with HIV-1 and HBV who have discontinued Truvada. Hepatic function should be monitored closely in these patients. If appropriate, initiation of anti-hepatitis B therapy may be warranted.
Truvada should not be coadministered with Atripla, Emtriva, Viread or lamivudine-containing products, including Combivir(R) (lamivudine/zidovudine), Epivir(R) or Epivir-HBV(R) (lamivudine), Epzicom(R) (abacavir sulfate/lamivudine) or Trizivir(R) (abacavir sulfate/lamivudine/zidovudine). In treatment-experienced patients, the use of Truvada should be guided by laboratory testing and treatment history.
Emtricitabine and tenofovir are principally eliminated by the kidneys. Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been reported in association with the use of Viread. It is recommended that creatinine clearance be calculated in all patients prior to initiating therapy with Truvada and as clinically appropriate during therapy.
Routine monitoring of calculated creatinine clearance and serum phosphorous should be performed in patients at risk for renal impairment including patients who have previously experienced renal events while receiving Hepsera(R) (adefovir dipivoxil).
Dosing interval adjustment and close monitoring of renal function are recommended in all patients with creatinine clearance 30-49 ml/min. Truvada should be avoided with concurrent or recent use of a nephrotoxic agent. Truvada should not be administered with Hepsera.
Coadministration of Truvada and didanosine should be undertaken with caution. Patients should be monitored closely for didanosine-associated adverse events and didanosine should be discontinued if these occur. Dose reduction of didanosine should be considered, if warranted. Patients on atazanavir and lopinavir/ritonavir plus Truvada should be monitored for Truvada-associated adverse events and Truvada should be discontinued if these occur. When co-administered with Truvada, it is recommended that atazanavir be boosted with ritonavir 100 mg. Atazanavir without ritonavir should not be co-administered with Truvada.
Decreases in bone mineral density (BMD) at the lumbar spine and hip have been seen with the use of Viread. The effect on long-term bone health and future fracture risk is unknown. BMD monitoring should be considered in patients with a history of pathologic fractures or who are at risk for osteopenia. Cases of osteomalacia (associated with proximal renal tubulopathy and which may contribute to fractures) have been reported in association with the use of Viread.
Changes in body fat have been observed in patients taking anti-HIV medicines. Immune Reconstitution Syndrome has been reported in patients treated with combination therapy, including Viread and Emtriva, and may necessitate further evaluation and treatment.
The most common adverse reactions (incidence greater-than or equal to 10 percent) are diarrhea, nausea, fatigue, headache, dizziness, depression, insomnia, abnormal dreams and rash.
About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company's mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North America, Europe and Australia.
Forward-Looking Statement
This press release includes forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995, that are subject to risks, uncertainties and other factors, including the risks that physicians may not prescribe Viread over other existing or future HBV medications. In addition, as Viread is used over longer periods of time by many patients with underlying health problems, taking numerous other medicines, safety, resistance, drug interaction or other issues may arise, which could reduce the market acceptance of Viread. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead's 2009 Annual report on Form 10-K and in Quarterly Reports on Form 10-Q for the first and second quarters of 2010, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.
U.S. full prescribing information for Viread is available at http://www.viread.com/. U.S. full prescribing information for Truvada is available at http://www.truvada.com/. U.S. full prescribing information for Hepsera is available at www.Hepsera.com.
Viread, Truvada and Hepsera are registered trademarks of Gilead Sciences, Inc.
For more information on Gilead Sciences, please visit the company's website at http://www.gilead.com/ or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.
SOURCE: Gilead Sciences, Inc.
Gilead Sciences, Inc.
Patrick O'Brien, 650-522-1936
Investors
or
Cara Miller, 650-522-1616
Media
Source
October 29, 2010
Alnylam Scientists to Present New Data on RNAi Therapeutics at the 61st Annual Meeting of the American Association for the Study of Liver Diseases
-- Research Highlights Include Potential New Therapeutic Applications for RNAi Therapeutics in Liver Fibrosis --
CAMBRIDGE, Mass., Oct 29, 2010 (BUSINESS WIRE) -- Alnylam Pharmaceuticals, Inc. /quotes/comstock/15*!alny/quotes/nls/alny (ALNY 13.14, -0.15, -1.13%) , a leading RNAi therapeutics company, announced today it will present several poster presentations at the 61st Annual Meeting of the American Association for the Study of Liver Diseases ("The Liver Meeting") being held in Boston, Mass from October 29 -- November 2, 2010. At the meeting, new research related to the company's pre-clinical and clinical pipeline efforts will be presented, including new data showing effective delivery of RNAi therapeutics to hepatic stellate cells. Pre-clinical data will also be presented on Alnylam's key development programs, including ALN-TTR01 for the treatment of transthyretin-mediated amyloidosis (ATTR), ALN-VSP for the treatment of liver cancers, and ALN-PCS for the treatment of hypercholesterolemia.
"The data we are presenting at this meeting highlight the significant progress we are making in advancing RNAi therapeutics to patients," said Akshay Vaishnaw, M.D., Ph.D., Senior Vice President, Clinical Research. "It is notable that we are now showing effective systemic delivery to stellate cells, creating a potentially new approach for the treatment of liver fibrosis with siRNAs targeting collagen 1a1. We are also pleased with additional updates from some of our key clinical development programs, including ALN-VSP, ALN-TTR01, and ALN-PCS."
In a poster titled "Liposome Mediated Delivery of siRNA to Hepatic Stellate Cells," Alnylam scientists will present new data on the systemic delivery of RNAi therapeutics to hepatic stellate cells (HSCs). HSCs play a key role in the initiation and progression of liver fibrosis, the excessive accumulation of tough, fibrous scar tissue that occurs in most types of chronic liver diseases. These new data show that siRNAs formulated in LNPs comprising the novel cationic lipid "C12-200" result in effective silencing of the HSC-specific gene target, collagen 1a1 (col1a1). These data point to a potential strategy for development of RNAi therapeutics for the treatment of fibrotic diseases.
Other presentations from Alnylam scientists at The Liver Meeting include the following:
a poster titled, "Carbohydrate Conjugation to siRNA for Liver-Specific Delivery" will describe progress made on improving stability and activity of GalNAc-conjugated siRNAs in vitro and their translation to improved in vivo gene silencing efficacy; a poster titled, "RNAi Therapeutics Targeting PCSK9 Result in Significant and Durable LDLc Lowering" will highlight pre-clinical data from the company's PCSK9 program which blocks the production of both intracellular and extracellular PCSK9 and uses a second generation LNP formulation; new data included in the poster will show the ability to utilize siRNA combination approaches to achieve efficient silencing of several genes at one time to achieve improved cholesterol lowering; in addition, new data will also be presented showing that lowering of PCSK9 in an LDLR heterozygous animal model of familial hypercholesterolemia results in a significant lowering of total cholesterol; a poster titled, "ALN-TTR, an RNAi Therapeutic for the Treatment of Transthyretin (TTR) Amyloidosis, Mediates Regression of Peripheral TTR Protein" will highlight pre-clinical data for the company's ALN-TTR01 program, which is currently in a Phase I clinical trial in patients with ATTR; and, a poster titled, "ALN-VSP, an Experimental RNAi Therapeutic, Demonstrates Efficacy in Tumor Model Studies" will review pre-clinical data for Alnylam's ALN-VSP program, which is currently in a Phase I clinical trial in patients with advanced solid tumors with liver involvement. Alnylam plans on providing an additional clinical update on the ALN-VSP program by the end of 2010.
About RNA Interference (RNAi)
RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today which was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. Small interfering RNAs (siRNAs), the molecules that mediate RNAi and comprise Alnylam's RNAi therapeutic platform, target the cause of diseases by potently silencing specific mRNAs, thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.
About Alnylam Pharmaceuticals
Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is applying its therapeutic expertise in RNAi to address significant medical needs, many of which cannot effectively be addressed with small molecules or antibodies, the current major classes of drugs. Alnylam is leading the translation of RNAi as a new class of innovative medicines with peer-reviewed research efforts published in the world's top scientific journals including Nature, Nature Medicine, and Cell. The company is leveraging these capabilities to build a broad pipeline of RNAi therapeutics for the treatment of a wide range of disease areas, including respiratory syncytial virus (RSV), liver cancers, TTR-mediated amyloidosis (ATTR), hypercholesterolemia, and Huntington's disease. In addition, Alnylam formed Alnylam Biotherapeutics, a division of the company focused on the development of RNAi technologies for application in manufacturing processes for biotherapeutic products, including recombinant proteins and monoclonal antibodies. The company's leadership position in fundamental patents, technology, and know-how relating to RNAi has enabled it to form major alliances with leading companies including Medtronic, Novartis, Biogen Idec, Roche, Takeda, Kyowa Hakko Kirin, and Cubist. Alnylam and Isis are joint owners of Regulus Therapeutics Inc., a company focused on the discovery, development, and commercialization of microRNA therapeutics. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, please visit http://www.alnylam.com/.
Alnylam Forward-Looking Statement
Various statements in this release concerning Alnylam's future expectations, plans and prospects, including without limitation, its expectations regarding the development of effective and efficient delivery approaches for RNAi therapeutics, including through delivery of RNAi therapeutics to hepatic stellate cells, and its expectations regarding the progress of its ongoing research and development programs for its RNAi therapeutic candidates, including ALN-VSP, ALN-TTR01, and ALN-PCS, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including Alnylam's ability to continue advancing its delivery efforts, including its efforts around delivery to hepatic stellate cells, discover and develop novel drug candidates, and successfully demonstrate efficacy and safety of its drug candidates, including ALN-VSP and ALN-TTR01, in human clinical trials, as well as those risks more fully discussed in the "Risk Factors" section of its most recent quarterly report on Form 10-Q on file with the Securities and Exchange Commission. In addition, any forward-looking statements represent Alnylam's views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam does not assume any obligation to update any forward-looking statements.
SOURCE: Alnylam Pharmaceuticals, Inc.
Alnylam Pharmaceuticals, Inc.
Cynthia Clayton (Investors), 617-551-8207
or
Spectrum
Amanda Sellers (Media), 202-955-6222 x2597
Source
CAMBRIDGE, Mass., Oct 29, 2010 (BUSINESS WIRE) -- Alnylam Pharmaceuticals, Inc. /quotes/comstock/15*!alny/quotes/nls/alny (ALNY 13.14, -0.15, -1.13%) , a leading RNAi therapeutics company, announced today it will present several poster presentations at the 61st Annual Meeting of the American Association for the Study of Liver Diseases ("The Liver Meeting") being held in Boston, Mass from October 29 -- November 2, 2010. At the meeting, new research related to the company's pre-clinical and clinical pipeline efforts will be presented, including new data showing effective delivery of RNAi therapeutics to hepatic stellate cells. Pre-clinical data will also be presented on Alnylam's key development programs, including ALN-TTR01 for the treatment of transthyretin-mediated amyloidosis (ATTR), ALN-VSP for the treatment of liver cancers, and ALN-PCS for the treatment of hypercholesterolemia.
"The data we are presenting at this meeting highlight the significant progress we are making in advancing RNAi therapeutics to patients," said Akshay Vaishnaw, M.D., Ph.D., Senior Vice President, Clinical Research. "It is notable that we are now showing effective systemic delivery to stellate cells, creating a potentially new approach for the treatment of liver fibrosis with siRNAs targeting collagen 1a1. We are also pleased with additional updates from some of our key clinical development programs, including ALN-VSP, ALN-TTR01, and ALN-PCS."
In a poster titled "Liposome Mediated Delivery of siRNA to Hepatic Stellate Cells," Alnylam scientists will present new data on the systemic delivery of RNAi therapeutics to hepatic stellate cells (HSCs). HSCs play a key role in the initiation and progression of liver fibrosis, the excessive accumulation of tough, fibrous scar tissue that occurs in most types of chronic liver diseases. These new data show that siRNAs formulated in LNPs comprising the novel cationic lipid "C12-200" result in effective silencing of the HSC-specific gene target, collagen 1a1 (col1a1). These data point to a potential strategy for development of RNAi therapeutics for the treatment of fibrotic diseases.
Other presentations from Alnylam scientists at The Liver Meeting include the following:
a poster titled, "Carbohydrate Conjugation to siRNA for Liver-Specific Delivery" will describe progress made on improving stability and activity of GalNAc-conjugated siRNAs in vitro and their translation to improved in vivo gene silencing efficacy; a poster titled, "RNAi Therapeutics Targeting PCSK9 Result in Significant and Durable LDLc Lowering" will highlight pre-clinical data from the company's PCSK9 program which blocks the production of both intracellular and extracellular PCSK9 and uses a second generation LNP formulation; new data included in the poster will show the ability to utilize siRNA combination approaches to achieve efficient silencing of several genes at one time to achieve improved cholesterol lowering; in addition, new data will also be presented showing that lowering of PCSK9 in an LDLR heterozygous animal model of familial hypercholesterolemia results in a significant lowering of total cholesterol; a poster titled, "ALN-TTR, an RNAi Therapeutic for the Treatment of Transthyretin (TTR) Amyloidosis, Mediates Regression of Peripheral TTR Protein" will highlight pre-clinical data for the company's ALN-TTR01 program, which is currently in a Phase I clinical trial in patients with ATTR; and, a poster titled, "ALN-VSP, an Experimental RNAi Therapeutic, Demonstrates Efficacy in Tumor Model Studies" will review pre-clinical data for Alnylam's ALN-VSP program, which is currently in a Phase I clinical trial in patients with advanced solid tumors with liver involvement. Alnylam plans on providing an additional clinical update on the ALN-VSP program by the end of 2010.
About RNA Interference (RNAi)
RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today which was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. Small interfering RNAs (siRNAs), the molecules that mediate RNAi and comprise Alnylam's RNAi therapeutic platform, target the cause of diseases by potently silencing specific mRNAs, thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.
About Alnylam Pharmaceuticals
Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is applying its therapeutic expertise in RNAi to address significant medical needs, many of which cannot effectively be addressed with small molecules or antibodies, the current major classes of drugs. Alnylam is leading the translation of RNAi as a new class of innovative medicines with peer-reviewed research efforts published in the world's top scientific journals including Nature, Nature Medicine, and Cell. The company is leveraging these capabilities to build a broad pipeline of RNAi therapeutics for the treatment of a wide range of disease areas, including respiratory syncytial virus (RSV), liver cancers, TTR-mediated amyloidosis (ATTR), hypercholesterolemia, and Huntington's disease. In addition, Alnylam formed Alnylam Biotherapeutics, a division of the company focused on the development of RNAi technologies for application in manufacturing processes for biotherapeutic products, including recombinant proteins and monoclonal antibodies. The company's leadership position in fundamental patents, technology, and know-how relating to RNAi has enabled it to form major alliances with leading companies including Medtronic, Novartis, Biogen Idec, Roche, Takeda, Kyowa Hakko Kirin, and Cubist. Alnylam and Isis are joint owners of Regulus Therapeutics Inc., a company focused on the discovery, development, and commercialization of microRNA therapeutics. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, please visit http://www.alnylam.com/.
Alnylam Forward-Looking Statement
Various statements in this release concerning Alnylam's future expectations, plans and prospects, including without limitation, its expectations regarding the development of effective and efficient delivery approaches for RNAi therapeutics, including through delivery of RNAi therapeutics to hepatic stellate cells, and its expectations regarding the progress of its ongoing research and development programs for its RNAi therapeutic candidates, including ALN-VSP, ALN-TTR01, and ALN-PCS, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including Alnylam's ability to continue advancing its delivery efforts, including its efforts around delivery to hepatic stellate cells, discover and develop novel drug candidates, and successfully demonstrate efficacy and safety of its drug candidates, including ALN-VSP and ALN-TTR01, in human clinical trials, as well as those risks more fully discussed in the "Risk Factors" section of its most recent quarterly report on Form 10-Q on file with the Securities and Exchange Commission. In addition, any forward-looking statements represent Alnylam's views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam does not assume any obligation to update any forward-looking statements.
SOURCE: Alnylam Pharmaceuticals, Inc.
Alnylam Pharmaceuticals, Inc.
Cynthia Clayton (Investors), 617-551-8207
or
Spectrum
Amanda Sellers (Media), 202-955-6222 x2597
Source
Spice in Curry Could Prevent Liver Damage
ScienceDaily (Oct. 29, 2010) — Curcumin, a chemical that gives curry its zing, holds promise in preventing or treating liver damage from an advanced form of a condition known as fatty liver disease, new Saint Louis University research suggests.
Curcurmin is contained in turmeric, a plant used by the Chinese to make traditional medicines for thousands of years. SLU's recent study highlights its potential in countering an increasingly common kind of fatty liver disease called non-alcoholic steatohepatitis (NASH). Linked to obesity and weight gain, NASH affects 3 to 4 percent of U.S. adults and can lead to a type of liver damage called liver fibrosis and possibly cirrhosis, liver cancer and death.
"My laboratory studies the molecular mechanism of liver fibrosis and is searching for natural ways to prevent and treat this liver damage," said Anping Chen, Ph.D., corresponding author and director of research in the pathology department of Saint Louis University.
"While research in an animal model and human clinical trials are needed, our study suggests that curcumin may be an effective therapy to treat and prevent liver fibrosis, which is associated with non-alcoholic steatohepatitis (NASH)."
High levels of blood leptin, glucose and insulin are commonly found in human patients with obesity and type 2 diabetes, which might contribute to NASH-associated liver fibrosis.
Chen's most recent work tested the effect of curcumin on the role of high levels of leptin in causing liver fibrosis in vitro, or in a controlled lab setting.
"Leptin plays a critical role in the development of liver fibrosis," he said.
High levels of leptin activate hepatic stellate cells, which are the cells that cause overproduction of the collagen protein, a major feature of liver fibrosis. The researchers found that among other activities, curcumin eliminated the effects of leptin on activating hepatic stellate cells, which short-circuited the development of liver damage.
The findings were published in the September issue of Endocrinology.
Source
Curcurmin is contained in turmeric, a plant used by the Chinese to make traditional medicines for thousands of years. SLU's recent study highlights its potential in countering an increasingly common kind of fatty liver disease called non-alcoholic steatohepatitis (NASH). Linked to obesity and weight gain, NASH affects 3 to 4 percent of U.S. adults and can lead to a type of liver damage called liver fibrosis and possibly cirrhosis, liver cancer and death.
"My laboratory studies the molecular mechanism of liver fibrosis and is searching for natural ways to prevent and treat this liver damage," said Anping Chen, Ph.D., corresponding author and director of research in the pathology department of Saint Louis University.
"While research in an animal model and human clinical trials are needed, our study suggests that curcumin may be an effective therapy to treat and prevent liver fibrosis, which is associated with non-alcoholic steatohepatitis (NASH)."
High levels of blood leptin, glucose and insulin are commonly found in human patients with obesity and type 2 diabetes, which might contribute to NASH-associated liver fibrosis.
Chen's most recent work tested the effect of curcumin on the role of high levels of leptin in causing liver fibrosis in vitro, or in a controlled lab setting.
"Leptin plays a critical role in the development of liver fibrosis," he said.
High levels of leptin activate hepatic stellate cells, which are the cells that cause overproduction of the collagen protein, a major feature of liver fibrosis. The researchers found that among other activities, curcumin eliminated the effects of leptin on activating hepatic stellate cells, which short-circuited the development of liver damage.
The findings were published in the September issue of Endocrinology.
Source
Bristol-Myers, Gilead Seek to Match AIDS Cocktail Success in Hepatitis C
Bristol-Myers Squibb Co. and Gilead Sciences Inc., makers of the top-selling combination pills for AIDS, are trying to duplicate their success to combat another evasive virus, hepatitis C.
The companies are among about a dozen that are developing drug cocktails more effective, less toxic and easier to take than current therapy. Hints of which blends may work will emerge next week, in research presented at a Boston meeting of the American Association for the Study of Liver Disease.
The pill combinations are designed to cure the liver- destroying hepatitis C virus without using interferon, a decades-old shot that causes a year of flu-like symptoms and works in only half of patients. While the virus outsmarted new mixtures in preliminary tests, study continues because the first blends to succeed will dominate a market that, according to Decision Resources Inc., may total $8 billion a year by 2014.
“We are trying to duplicate the paradigm that revolutionized HIV therapy well over a decade ago, and apply those lessons learned to hepatitis C,” said Ira Jacobson, medical director of the Center for the Study of Hepatitis C, a New York-based program of Rockefeller University, Weill Cornell Medical College, and New York-Presbyterian Hospital. “My belief is if we suppress it profoundly enough, the virus will eventually wither away and be eradicated in the liver.”
The shares of New York-based Bristol-Myers decreased 16 cents to $26.83 at 11:10 a.m. in New York Stock Exchange composite trading. Gilead, of Foster City, California, fell 2 cents to $39.84 in Nasdaq Stock Market composite trading.
200 Million People
About 200 million people worldwide have hepatitis C, an analysis at Dartmouth Medical School in Hanover, New Hampshire, found. The disease often persists as a chronic condition that causes nausea, weakness and exhaustion as it destroys the liver over the course of years or decades.
Interferon, the standard of care when paired with the generic drug ribavirin to increase potency, works by boosting the immune system. Roche Holding AG of Basel, Switzerland sells a version of interferon under the brand name Pegasys, while Merck & Co. of Whitehouse Station, New Jersey sells a form called PegIntron.
Two new hepatitis C options that may be introduced next year are telaprevir, from Cambridge, Massachusetts-based Vertex Pharmaceuticals Inc. and New Brunswick, New Jersey-based Johnson & Johnson, and boceprevir, from Whitehouse Station, New Jersey- based Merck & Co. The drugs are similar to the family of AIDS medicines called protease inhibitors that prevent viruses from replicating. Both are used with interferon and ribavirin.
$3 Billion
The combinations are expected to generate more than $3 billion in sales annually by 2013, with telaprevir accounting for $2.6 billion, said Howard Liang, an analyst at Leerink Swann & Co. in Boston, in a telephone interview.
The new antiviral combinations are oral drugs, not injections, and may have the potential to cure patients who haven’t benefitted from the older products, Liang said.
“Both clinicians and patients would prefer drugs that lack the side effects of interferon and ribavirin,” said Alexandra Makarova, an analyst at Decision Resources, a research company in Burlington, Massachusetts, in a telephone interview. “If the combination of direct antivirals will allow doctors to exclude interferon and ribavirin, it could spoil the party for those regimens.”
Optimal Combination
Research hasn’t identified the optimal oral combination for hepatitis C. Initial reports show treatment with just one pill or low-dose combinations aren’t enough to keep the virus in check, and investigators are building more, and more-powerful, combinations. The U.S. Food and Drug Administration, which initially rejected efforts to study treatments without interferon and ribavirin, has now let trials begin.
The ability to create liver cells from stem cells, breed mice that are better models for hepatitis C, and isolate cells from human livers infected with the virus are making it easier to identify and pull together the best cocktails before they are tested in humans, said Michael Charlton, director of the liver transplant program at the Mayo Clinic in Rochester, Minnesota.
“The door may be opening to more innovative combinations of oral therapies,” said Charlton, who sees a new patient every 30 minutes, on average, when working in Minneapolis. “There is still a tremendous second and third wave of drug combinations that are being explored,” he said in a telephone interview.
Second-Stage Tests
Bristol-Myers will present results at the Boston meeting from second-stage tests combining an experimental protease inhibitor, similar to those used for AIDS, with a pill from new family of virus-fighting medicines. The two ingredients, called BMS-790052 and BMS-650032 stopped working in as little as three weeks. Adding interferon and ribavirin to the two-drug cocktail suppressed the virus for as long as three months.
Gilead will report outcomes from a monthlong study of its experimental protease inhibitor, GS-9256, with a second new drug, GS-9190, which is in a different family of medicines.
Adding ribavirin alone delayed or reduced the breakthrough virus, the study found. Vertex stopped a low-dose combination of telaprevir and its experimental drug VX-222 after the virus broke through during the first month of treatment. A higher-dose combination is undergoing tests.
The combination approach is being pursued by biotechnology companies, among them Pharmasset Inc. of Princeton, New Jersey; Medivir AB of Huddinge, Sweden; Idenix Pharmaceuticals Inc. of Cambridge, Massachusetts; and Inhibitex Inc. of Alpharetta, Georgia.
Merck Developments
Merck is developing several oral hepatitis C drugs internally, while looking for outsiders to become partners on its compounds, said Lisa Pedicone, global director of scientific affairs for the company’s hepatitis C products.
A combination of two oral drugs from Roche and Pharmasset was able to keep the virus in check during an initial 13-day study. The combination includes a protease inhibitor and another medicine polymerase inhibitor.
“We need to be bringing the people who have all these agents together to sit down at the same table,” Charlton said. “It takes someone with deep resources to develop a multidrug cocktail.”
Preliminary data suggest that a new family of medicines known as nucleoside-based polymerase inhibitors, which block an enzyme the virus needs to thrive, may be a key player in the drug combinations, Leerink’s Liang said. Pharmasset and Idenix are among the few companies working with those drugs, making them desirable partners or potential takeover targets, he said.
‘Early Days’
“This is like the early days of HIV,” said Stuart Ray, director of the infectious-diseases fellowship training program at Johns Hopkins University School of Medicine in Baltimore. “We are trying to weigh the safety of getting these drugs when they are first available, against the risk of waiting when we know liver disease is likely to be progressing in all of our patients.”
To contact the reporter on this story: Michelle Fay Cortez in Minneapolis at mcortez@bloomberg.net
To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.ne t
Source
The companies are among about a dozen that are developing drug cocktails more effective, less toxic and easier to take than current therapy. Hints of which blends may work will emerge next week, in research presented at a Boston meeting of the American Association for the Study of Liver Disease.
The pill combinations are designed to cure the liver- destroying hepatitis C virus without using interferon, a decades-old shot that causes a year of flu-like symptoms and works in only half of patients. While the virus outsmarted new mixtures in preliminary tests, study continues because the first blends to succeed will dominate a market that, according to Decision Resources Inc., may total $8 billion a year by 2014.
“We are trying to duplicate the paradigm that revolutionized HIV therapy well over a decade ago, and apply those lessons learned to hepatitis C,” said Ira Jacobson, medical director of the Center for the Study of Hepatitis C, a New York-based program of Rockefeller University, Weill Cornell Medical College, and New York-Presbyterian Hospital. “My belief is if we suppress it profoundly enough, the virus will eventually wither away and be eradicated in the liver.”
The shares of New York-based Bristol-Myers decreased 16 cents to $26.83 at 11:10 a.m. in New York Stock Exchange composite trading. Gilead, of Foster City, California, fell 2 cents to $39.84 in Nasdaq Stock Market composite trading.
200 Million People
About 200 million people worldwide have hepatitis C, an analysis at Dartmouth Medical School in Hanover, New Hampshire, found. The disease often persists as a chronic condition that causes nausea, weakness and exhaustion as it destroys the liver over the course of years or decades.
Interferon, the standard of care when paired with the generic drug ribavirin to increase potency, works by boosting the immune system. Roche Holding AG of Basel, Switzerland sells a version of interferon under the brand name Pegasys, while Merck & Co. of Whitehouse Station, New Jersey sells a form called PegIntron.
Two new hepatitis C options that may be introduced next year are telaprevir, from Cambridge, Massachusetts-based Vertex Pharmaceuticals Inc. and New Brunswick, New Jersey-based Johnson & Johnson, and boceprevir, from Whitehouse Station, New Jersey- based Merck & Co. The drugs are similar to the family of AIDS medicines called protease inhibitors that prevent viruses from replicating. Both are used with interferon and ribavirin.
$3 Billion
The combinations are expected to generate more than $3 billion in sales annually by 2013, with telaprevir accounting for $2.6 billion, said Howard Liang, an analyst at Leerink Swann & Co. in Boston, in a telephone interview.
The new antiviral combinations are oral drugs, not injections, and may have the potential to cure patients who haven’t benefitted from the older products, Liang said.
“Both clinicians and patients would prefer drugs that lack the side effects of interferon and ribavirin,” said Alexandra Makarova, an analyst at Decision Resources, a research company in Burlington, Massachusetts, in a telephone interview. “If the combination of direct antivirals will allow doctors to exclude interferon and ribavirin, it could spoil the party for those regimens.”
Optimal Combination
Research hasn’t identified the optimal oral combination for hepatitis C. Initial reports show treatment with just one pill or low-dose combinations aren’t enough to keep the virus in check, and investigators are building more, and more-powerful, combinations. The U.S. Food and Drug Administration, which initially rejected efforts to study treatments without interferon and ribavirin, has now let trials begin.
The ability to create liver cells from stem cells, breed mice that are better models for hepatitis C, and isolate cells from human livers infected with the virus are making it easier to identify and pull together the best cocktails before they are tested in humans, said Michael Charlton, director of the liver transplant program at the Mayo Clinic in Rochester, Minnesota.
“The door may be opening to more innovative combinations of oral therapies,” said Charlton, who sees a new patient every 30 minutes, on average, when working in Minneapolis. “There is still a tremendous second and third wave of drug combinations that are being explored,” he said in a telephone interview.
Second-Stage Tests
Bristol-Myers will present results at the Boston meeting from second-stage tests combining an experimental protease inhibitor, similar to those used for AIDS, with a pill from new family of virus-fighting medicines. The two ingredients, called BMS-790052 and BMS-650032 stopped working in as little as three weeks. Adding interferon and ribavirin to the two-drug cocktail suppressed the virus for as long as three months.
Gilead will report outcomes from a monthlong study of its experimental protease inhibitor, GS-9256, with a second new drug, GS-9190, which is in a different family of medicines.
Adding ribavirin alone delayed or reduced the breakthrough virus, the study found. Vertex stopped a low-dose combination of telaprevir and its experimental drug VX-222 after the virus broke through during the first month of treatment. A higher-dose combination is undergoing tests.
The combination approach is being pursued by biotechnology companies, among them Pharmasset Inc. of Princeton, New Jersey; Medivir AB of Huddinge, Sweden; Idenix Pharmaceuticals Inc. of Cambridge, Massachusetts; and Inhibitex Inc. of Alpharetta, Georgia.
Merck Developments
Merck is developing several oral hepatitis C drugs internally, while looking for outsiders to become partners on its compounds, said Lisa Pedicone, global director of scientific affairs for the company’s hepatitis C products.
A combination of two oral drugs from Roche and Pharmasset was able to keep the virus in check during an initial 13-day study. The combination includes a protease inhibitor and another medicine polymerase inhibitor.
“We need to be bringing the people who have all these agents together to sit down at the same table,” Charlton said. “It takes someone with deep resources to develop a multidrug cocktail.”
Preliminary data suggest that a new family of medicines known as nucleoside-based polymerase inhibitors, which block an enzyme the virus needs to thrive, may be a key player in the drug combinations, Leerink’s Liang said. Pharmasset and Idenix are among the few companies working with those drugs, making them desirable partners or potential takeover targets, he said.
‘Early Days’
“This is like the early days of HIV,” said Stuart Ray, director of the infectious-diseases fellowship training program at Johns Hopkins University School of Medicine in Baltimore. “We are trying to weigh the safety of getting these drugs when they are first available, against the risk of waiting when we know liver disease is likely to be progressing in all of our patients.”
To contact the reporter on this story: Michelle Fay Cortez in Minneapolis at mcortez@bloomberg.net
To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.ne t
Source
Olive Oil Protects Liver
Article Date: 29 Oct 2010 - 1:00 PDT
Extra-virgin olive oil can protect the liver from oxidative stress. Researchers writing in BioMed Central's open access journal Nutrition and Metabolism exposed rats to a moderately toxic herbicide known to deplete antioxidants and cause oxidative stress, finding that those rats fed on a diet containing the olive oil were partially protected from the resulting liver damage.
Mohamed Hammami from the University of Monastir, Tunisia and King Saud University, Riyadh, Saudi Arabia, worked with a team of researchers to carry out the experiments in a group of 80 rats. He said, "Olive oil is an integral ingredient in the Mediterranean diet. There is growing evidence that it may have great health benefits including the reduction in coronary heart disease risk, the prevention of some cancers and the modification of immune and inflammatory responses. Here, we've shown that extra virgin olive oil and its extracts protect against oxidative damage of hepatic tissue".
The researchers separated the rats into a control group, an olive oil group, and 6 groups that were exposed to the herbicide '2,4-Dichlorophenoxyacetic acid' with or without either whole olive oil, or one of two oil extracts the hydrophilic fraction or the lipophilic fraction. All rats given the herbicide showed signs of significant liver damage. However, extra virgin olive oil and hydrophilic fraction intake induced a significant increase in antioxidant enzyme activity and a decrease in markers of liver damage.
Speaking about the results, Hammami said, "The hydrophilic fraction of olive oil seems to be the effective one in reducing toxin-induced oxidative stress, indicating that hydrophilic extract may exert a direct antioxidant effect on hepatic cells. However, more detailed studies about the effect of antioxidant compounds separately and/or their interactions are necessary to substantiate these observations".
Sources: BioMed Central Limited, AlphaGalileo Foundation.
Source
Extra-virgin olive oil can protect the liver from oxidative stress. Researchers writing in BioMed Central's open access journal Nutrition and Metabolism exposed rats to a moderately toxic herbicide known to deplete antioxidants and cause oxidative stress, finding that those rats fed on a diet containing the olive oil were partially protected from the resulting liver damage.
Mohamed Hammami from the University of Monastir, Tunisia and King Saud University, Riyadh, Saudi Arabia, worked with a team of researchers to carry out the experiments in a group of 80 rats. He said, "Olive oil is an integral ingredient in the Mediterranean diet. There is growing evidence that it may have great health benefits including the reduction in coronary heart disease risk, the prevention of some cancers and the modification of immune and inflammatory responses. Here, we've shown that extra virgin olive oil and its extracts protect against oxidative damage of hepatic tissue".
The researchers separated the rats into a control group, an olive oil group, and 6 groups that were exposed to the herbicide '2,4-Dichlorophenoxyacetic acid' with or without either whole olive oil, or one of two oil extracts the hydrophilic fraction or the lipophilic fraction. All rats given the herbicide showed signs of significant liver damage. However, extra virgin olive oil and hydrophilic fraction intake induced a significant increase in antioxidant enzyme activity and a decrease in markers of liver damage.
Speaking about the results, Hammami said, "The hydrophilic fraction of olive oil seems to be the effective one in reducing toxin-induced oxidative stress, indicating that hydrophilic extract may exert a direct antioxidant effect on hepatic cells. However, more detailed studies about the effect of antioxidant compounds separately and/or their interactions are necessary to substantiate these observations".
Sources: BioMed Central Limited, AlphaGalileo Foundation.
Source
Medivir to Hold Conference Call and Breakfast Meeting to Discuss TMC435 Data Presented at the 61st AASLD Meeting
- Data Includes a Late-breaking Oral Presentation of 24-Week Interim Data of the TMC435 phase 2b PILLAR Study -
HUDDINGE, Sweden, Oct 29, 2010 (BUSINESS WIRE) -- Regulatory News:Medivir AB (omx:MVIR), a research-based specialty pharmaceutical company focused on infectious diseases will hold a conference call for analysts and investors and a breakfast meeting in Boston, USA, for US based investors, analysts and media on Tuesday 2nd November 2010. Both events will discuss Medivir's lead development product TMC435, a once-daily hepatitis C protease inhibitor in phase 2b development, which is being jointly developed by Medivir and Tibotec Pharmaceuticals.
Hosts, Rein Piir (CFO/IR), Bertil Samuelsson, (CSO) and Asa Rosenquist, (Director Medicinal Chemistry) will provide an update on the development of TMC435, which is the subject of four posters and one oral presentation being presented at the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), taking place from 29 October to 2 November 2010 in Boston, USA.
The details are as follows:
Conference Call For Analysts and Investors:
Tuesday, November 2, 2010 at 6.30am EDT / 10.30am GMT / 11.30am CET Please register for the conference call online at: http://invite.taylor-rafferty.com/_Medivir/ConferenceCall
You will receive the dial-in and replay numbers for the conference call following your online registration.
Breakfast Meeting for US based Analysts, Investors and Media
Tuesday November 2, 2010 at 7:00am -- 8.30am EDT (breakfast will be served between 7:00am -- 7.30am EDT) Venue: Colonnade Hotel, Braemore & Kenmore Room 120 Huntington Avenue, Boston Please confirm your participation by registering on-line: http://invite.taylor-rafferty.com/_Medivir/Breakfast/default.htm
For enquiries please contact: Lindsey Neville at M:Communications on +44 (0)20 7920 2333 or Jason Marshall on +1 212 889 4350 or email Neville@mcomgroup.com
Accepted titles for Abstracts to be presented at the 2010 AASLD meeting are as follows:
Late Breaker Oral Presentation for presentation at Monday 1 Nov. 17:45 (EST): LB-5. "Efficacy and safety of TMC435 in combination with peginterferon a-2a and ribavirin in treatment-naive genotype-1 HCV patients: 24-week interim results from the PILLAR study."
Poster Presentations:
278. "In vitro studies investigating the mechanism of interaction between TMC435 and hepatic transporters." To be presented: Saturday 30 Oct, 14:00 (EST)
812. "Virologic analysis of genotype-1-infected patients treated with once-daily TMC435 during the Optimal Protease inhibitor Enhancement of Response to Therapy (OPERA)-1 study." To be presented: Sunday 31 Oct, 08:00 (EST)
895. "A Phase IIa, open-label study to assess the antiviral activity of TMC435 monotherapy in patients infected with HCV genotypes 2--6." To be presented: Sunday 31 Oct, 08:00 (EST)
1873. "Pharmacokinetic-pharmacodynamic analyses of TMC435 in patients infected with Hepatitis C Virus (HCV) genotypes 2 to 6." To be presented: Tuesday 2 Nov, 07:00 (EST).
About Medivir
Medivir is a research-based specialty pharmaceutical company focused on the development of high-value treatments for infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development. Medivir has a strong R&D portfolio and has recently launched its first product Xerese(TM)/Xerclear(R). Medivir's key pipeline asset, TMC435, a protease inhibitor, is in phase 2b clinical development for Hepatitis C and is partnered with Tibotec Pharmaceuticals.
Xerese(TM)/Xerclear(R) is an innovative treatment for cold sores, which has been approved in both the US and Europe. It is partnered with GSK to be sold OTC in Europe and Russia and with Meda in North America. Medivir has retained the Rx rights for Xerclear(R) in Sweden and Finland.
For more information about Medivir, please visit the Company's website: http://www.medivir.se/.
About TMC435 clinical trial programs
TMC435 is a once daily protease inhibitor jointly developed by Medivir and Tibotec Pharmaceuticals to treat hepatitis C virus infections. TMC435 is currently being studied in three phase 2b clinical trials (TMC435-C205, TMC435-C206 and TMC435-C215) in genotype 1 (G1) treatment-naive and in G1 patients that failed previous IFN-based treatment. TMC435 is planned to enter phase 3 studies early 2011.
PILLAR Study (TMC435-C205)
TMC435-C205 is an ongoing randomized double-blind global phase 2b study in 386 genotype-1 treatment-naive patients. It evaluates once daily treatment of TMC435 with different doses and durations given in addition to standard of care treatment, consisting of ribavirin and pegIFNalpha-2A.
ASPIRE Study (TMC435-C206)
TMC435-C206 is an ongoing randomized double-blind global phase 2b study in 463 genotype-1 treatment-experienced patients. It evaluates once daily treatment of TMC435 in with different doses of given in addition to standard of care treatment, consisting of ribavirin and pegIFNalpha-2A.
TMC435-C215
TMC435-C215 is an ongoing Japanese phase 2b study in 92 genotype-1 treatment-naive patients. It evaluates once daily treatment of TMC435 with different doses and durations given in addition to standard of care treatment, consisting of ribavirin and pegIFNalpha-2A.
Opera-2 (TMC435-C202)
TMC435-C202 is a completed phase 2a study in treatment-naive genotype 2 to 6 HCV patients. It is a once daily treatment of TMC435 during seven days, at 200 mg. Subsequently, patients could continue with Standard of Care treatment consisting of pegylated interferon and ribavirin upon agreement with the study doctor.
About Hepatitis C
Hepatitis C is a blood-borne infectious disease of the liver and is a leading cause of chronic liver disease and liver transplants. The WHO estimates that nearly 180 million people worldwide, or approximately 3% of the world's population, are infected with hepatitis C virus (HCV). The CDC has reported that almost three million people in the United States are chronically infected with HCV.
This information was brought to you by Cision http://www.cisionwire.com/
SOURCE: Medivir
Medivir
CFO & VP Investor Relations Office:
Rein Piir, +46 8 546 831 23
Mobile: +46 708 537 292
http://www.medivir.seor/
M:Communications
Europe:
Mary-Jane Elliott/Emma Thompson/Amber Bielecka, +44(0)20 7920 2330
or
USA:
Jason Marshall, +1 212 897 5497
Medivir@mcomgroup.com
Source
HUDDINGE, Sweden, Oct 29, 2010 (BUSINESS WIRE) -- Regulatory News:Medivir AB (omx:MVIR), a research-based specialty pharmaceutical company focused on infectious diseases will hold a conference call for analysts and investors and a breakfast meeting in Boston, USA, for US based investors, analysts and media on Tuesday 2nd November 2010. Both events will discuss Medivir's lead development product TMC435, a once-daily hepatitis C protease inhibitor in phase 2b development, which is being jointly developed by Medivir and Tibotec Pharmaceuticals.
Hosts, Rein Piir (CFO/IR), Bertil Samuelsson, (CSO) and Asa Rosenquist, (Director Medicinal Chemistry) will provide an update on the development of TMC435, which is the subject of four posters and one oral presentation being presented at the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), taking place from 29 October to 2 November 2010 in Boston, USA.
The details are as follows:
Conference Call For Analysts and Investors:
Tuesday, November 2, 2010 at 6.30am EDT / 10.30am GMT / 11.30am CET Please register for the conference call online at: http://invite.taylor-rafferty.com/_Medivir/ConferenceCall
You will receive the dial-in and replay numbers for the conference call following your online registration.
Breakfast Meeting for US based Analysts, Investors and Media
Tuesday November 2, 2010 at 7:00am -- 8.30am EDT (breakfast will be served between 7:00am -- 7.30am EDT) Venue: Colonnade Hotel, Braemore & Kenmore Room 120 Huntington Avenue, Boston Please confirm your participation by registering on-line: http://invite.taylor-rafferty.com/_Medivir/Breakfast/default.htm
For enquiries please contact: Lindsey Neville at M:Communications on +44 (0)20 7920 2333 or Jason Marshall on +1 212 889 4350 or email Neville@mcomgroup.com
Accepted titles for Abstracts to be presented at the 2010 AASLD meeting are as follows:
Late Breaker Oral Presentation for presentation at Monday 1 Nov. 17:45 (EST): LB-5. "Efficacy and safety of TMC435 in combination with peginterferon a-2a and ribavirin in treatment-naive genotype-1 HCV patients: 24-week interim results from the PILLAR study."
Poster Presentations:
278. "In vitro studies investigating the mechanism of interaction between TMC435 and hepatic transporters." To be presented: Saturday 30 Oct, 14:00 (EST)
812. "Virologic analysis of genotype-1-infected patients treated with once-daily TMC435 during the Optimal Protease inhibitor Enhancement of Response to Therapy (OPERA)-1 study." To be presented: Sunday 31 Oct, 08:00 (EST)
895. "A Phase IIa, open-label study to assess the antiviral activity of TMC435 monotherapy in patients infected with HCV genotypes 2--6." To be presented: Sunday 31 Oct, 08:00 (EST)
1873. "Pharmacokinetic-pharmacodynamic analyses of TMC435 in patients infected with Hepatitis C Virus (HCV) genotypes 2 to 6." To be presented: Tuesday 2 Nov, 07:00 (EST).
About Medivir
Medivir is a research-based specialty pharmaceutical company focused on the development of high-value treatments for infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development. Medivir has a strong R&D portfolio and has recently launched its first product Xerese(TM)/Xerclear(R). Medivir's key pipeline asset, TMC435, a protease inhibitor, is in phase 2b clinical development for Hepatitis C and is partnered with Tibotec Pharmaceuticals.
Xerese(TM)/Xerclear(R) is an innovative treatment for cold sores, which has been approved in both the US and Europe. It is partnered with GSK to be sold OTC in Europe and Russia and with Meda in North America. Medivir has retained the Rx rights for Xerclear(R) in Sweden and Finland.
For more information about Medivir, please visit the Company's website: http://www.medivir.se/.
About TMC435 clinical trial programs
TMC435 is a once daily protease inhibitor jointly developed by Medivir and Tibotec Pharmaceuticals to treat hepatitis C virus infections. TMC435 is currently being studied in three phase 2b clinical trials (TMC435-C205, TMC435-C206 and TMC435-C215) in genotype 1 (G1) treatment-naive and in G1 patients that failed previous IFN-based treatment. TMC435 is planned to enter phase 3 studies early 2011.
PILLAR Study (TMC435-C205)
TMC435-C205 is an ongoing randomized double-blind global phase 2b study in 386 genotype-1 treatment-naive patients. It evaluates once daily treatment of TMC435 with different doses and durations given in addition to standard of care treatment, consisting of ribavirin and pegIFNalpha-2A.
ASPIRE Study (TMC435-C206)
TMC435-C206 is an ongoing randomized double-blind global phase 2b study in 463 genotype-1 treatment-experienced patients. It evaluates once daily treatment of TMC435 in with different doses of given in addition to standard of care treatment, consisting of ribavirin and pegIFNalpha-2A.
TMC435-C215
TMC435-C215 is an ongoing Japanese phase 2b study in 92 genotype-1 treatment-naive patients. It evaluates once daily treatment of TMC435 with different doses and durations given in addition to standard of care treatment, consisting of ribavirin and pegIFNalpha-2A.
Opera-2 (TMC435-C202)
TMC435-C202 is a completed phase 2a study in treatment-naive genotype 2 to 6 HCV patients. It is a once daily treatment of TMC435 during seven days, at 200 mg. Subsequently, patients could continue with Standard of Care treatment consisting of pegylated interferon and ribavirin upon agreement with the study doctor.
About Hepatitis C
Hepatitis C is a blood-borne infectious disease of the liver and is a leading cause of chronic liver disease and liver transplants. The WHO estimates that nearly 180 million people worldwide, or approximately 3% of the world's population, are infected with hepatitis C virus (HCV). The CDC has reported that almost three million people in the United States are chronically infected with HCV.
This information was brought to you by Cision http://www.cisionwire.com/
SOURCE: Medivir
Medivir
CFO & VP Investor Relations Office:
Rein Piir, +46 8 546 831 23
Mobile: +46 708 537 292
http://www.medivir.seor/
M:Communications
Europe:
Mary-Jane Elliott/Emma Thompson/Amber Bielecka, +44(0)20 7920 2330
or
USA:
Jason Marshall, +1 212 897 5497
Medivir@mcomgroup.com
Source
High hepatitis C mortality and low clearance rates in HIV/HCV-co-infected patients in France
Michael Carter
Published: 29 October 2010
Mortality rates are high among French patients co-infected with HIV and hepatitis C, investigators report in BMC Infectious Diseases. Over 40% of deaths were directly attributable to hepatitis C.
Only a fifth of patients with hepatitis C genotype 1 and 36% of those with genotype 4 treated since 2005 had a successful response to treatment, a finding broadly in line with the results of clinical trials in coinfected people. Only 21% of patients in the French cohort had HCV genotypes 2 or 3, which have proved more likely to respond to treatment.
A low overall success rate was seen in individuals who received a second course of treatment for hepatitis C.
However, treatment for depression not only improved mood but also fatigue and other aspects of health.
Approximately a quarter of HIV-positive patients in France are co-infected with hepatitis C. Investigators wanted to gain a better understanding of these patients, and in 2005 established ANRS CO 13 HEPAVIH cohort.
The investigators describe the cohort as “a unique nation-wide collaboration of HIV treatment, infectious diseases, internal medicine and hepatology centres.”
Between 2006 and 2008 a total of 1175 adults were recruited to the cohort. All were HIV-positive, 1048 had chronic hepatitis C infection and 127 had had a sustained response to hepatitis C therapy.
The patients’ median age was 45 years, 70% were men, their median CD4 cell count was 442 cells/mm3 and 68% had an undetectable HIV viral load.
Most of the patients (71%) were infected with hepatitis C through injecting drug use and the median time since diagnosis of hepatitis C was ten years. The median hepatitis C viral load was 6.2 logUI/ml.
A variety of tests were used to assess the extent of liver damage caused by hepatitis C. The proportion of patients diagnosed with cirrhosis varied according to which test was used.
FibroTest detected cirrhosis in 46% of patients, FibroScan in 30% and a liver biopsy in 27%. Nevertheless, all the tests had a high positive predictive value for cirrhosis diagnosis.
At the time of enrolment to the cohort, 72% of patients were taking antiretroviral therapy. The majority of patients (58%) were taking a combination of drugs based on a ritonavir-boosted protease inhibitor.
Overall, 51% of patients had received hepatitis C therapy. Most (35)% received this treatment before they entered the cohort.
Outcome data were available for 127 patients who had received hepatitis C treatment after entering the cohort.
A total of 32% had a sustained virologic response. The clearance rate was 34% for those taking anti-hepatitis C drugs for the first time, and fell to 27% for individuals taking a second course of therapy.
Outcomes were also analysed according to hepatitis C genotype. Only 20% of patients infected with genotype 1 had a successful response to therapy, and 36% of those with genotype 4 cleared the infection.
By January 2010, a total of 13 new cases of cirrhosis had been diagnosed. All were in patients with chronic hepatitis C. There were nine new cases of liver cancer, three of which were in patients who had had a sustained response to therapy with anti-hepatitis C drugs.
There were 49 deaths, and 41% were attributed to hepatitis C.
The investigators calculated that the rate of severe hepatitis C-related events was 2 per 100 person years of follow-up.
Event rates were notably higher in patients with cirrhosis (7 vs. 0.35 per 100 person years). The investigators note that this was expected, but nevertheless emphasised the importance of accurately diagnosing cirrhosis. All three types of tests detected over 99% of cases of cirrhosis.
A low baseline CD4 cell count (below 200 cells/mm3) also significantly increased the risk of a serious hepatitis C-related outcome (5.5 vs. 1.4 per 100 person years; p = 0.002). Patients co-infected with hepatitis C are especially recommended to start antiretroviral therapy when their CD4 cell count is around 350 cells/mm3.
Using information gathered from questionnaires completed by the patients, the investigators found that treating depression not only improved mood, but also had an impact on fatigue, as well as boosting cognitive, physical and social functioning.
The researchers conclude that cohorts such as theirs “will be critical to address future clinical and public health questions of chronic diseases of infectious origin”.
Reference
Loko M-A et al. The French national prospective cohort of patients co-infected with HIV and HCV (ANRS CO13 HEPAVIH): Early findings, 2006-2010. BMC Infectious Diseases, 10: 303doi:10.1186/1471-2334-10-303, 2010 (click here for access to article text).
Source
Published: 29 October 2010
Mortality rates are high among French patients co-infected with HIV and hepatitis C, investigators report in BMC Infectious Diseases. Over 40% of deaths were directly attributable to hepatitis C.
Only a fifth of patients with hepatitis C genotype 1 and 36% of those with genotype 4 treated since 2005 had a successful response to treatment, a finding broadly in line with the results of clinical trials in coinfected people. Only 21% of patients in the French cohort had HCV genotypes 2 or 3, which have proved more likely to respond to treatment.
A low overall success rate was seen in individuals who received a second course of treatment for hepatitis C.
However, treatment for depression not only improved mood but also fatigue and other aspects of health.
Approximately a quarter of HIV-positive patients in France are co-infected with hepatitis C. Investigators wanted to gain a better understanding of these patients, and in 2005 established ANRS CO 13 HEPAVIH cohort.
The investigators describe the cohort as “a unique nation-wide collaboration of HIV treatment, infectious diseases, internal medicine and hepatology centres.”
Between 2006 and 2008 a total of 1175 adults were recruited to the cohort. All were HIV-positive, 1048 had chronic hepatitis C infection and 127 had had a sustained response to hepatitis C therapy.
The patients’ median age was 45 years, 70% were men, their median CD4 cell count was 442 cells/mm3 and 68% had an undetectable HIV viral load.
Most of the patients (71%) were infected with hepatitis C through injecting drug use and the median time since diagnosis of hepatitis C was ten years. The median hepatitis C viral load was 6.2 logUI/ml.
A variety of tests were used to assess the extent of liver damage caused by hepatitis C. The proportion of patients diagnosed with cirrhosis varied according to which test was used.
FibroTest detected cirrhosis in 46% of patients, FibroScan in 30% and a liver biopsy in 27%. Nevertheless, all the tests had a high positive predictive value for cirrhosis diagnosis.
At the time of enrolment to the cohort, 72% of patients were taking antiretroviral therapy. The majority of patients (58%) were taking a combination of drugs based on a ritonavir-boosted protease inhibitor.
Overall, 51% of patients had received hepatitis C therapy. Most (35)% received this treatment before they entered the cohort.
Outcome data were available for 127 patients who had received hepatitis C treatment after entering the cohort.
A total of 32% had a sustained virologic response. The clearance rate was 34% for those taking anti-hepatitis C drugs for the first time, and fell to 27% for individuals taking a second course of therapy.
Outcomes were also analysed according to hepatitis C genotype. Only 20% of patients infected with genotype 1 had a successful response to therapy, and 36% of those with genotype 4 cleared the infection.
By January 2010, a total of 13 new cases of cirrhosis had been diagnosed. All were in patients with chronic hepatitis C. There were nine new cases of liver cancer, three of which were in patients who had had a sustained response to therapy with anti-hepatitis C drugs.
There were 49 deaths, and 41% were attributed to hepatitis C.
The investigators calculated that the rate of severe hepatitis C-related events was 2 per 100 person years of follow-up.
Event rates were notably higher in patients with cirrhosis (7 vs. 0.35 per 100 person years). The investigators note that this was expected, but nevertheless emphasised the importance of accurately diagnosing cirrhosis. All three types of tests detected over 99% of cases of cirrhosis.
A low baseline CD4 cell count (below 200 cells/mm3) also significantly increased the risk of a serious hepatitis C-related outcome (5.5 vs. 1.4 per 100 person years; p = 0.002). Patients co-infected with hepatitis C are especially recommended to start antiretroviral therapy when their CD4 cell count is around 350 cells/mm3.
Using information gathered from questionnaires completed by the patients, the investigators found that treating depression not only improved mood, but also had an impact on fatigue, as well as boosting cognitive, physical and social functioning.
The researchers conclude that cohorts such as theirs “will be critical to address future clinical and public health questions of chronic diseases of infectious origin”.
Reference
Loko M-A et al. The French national prospective cohort of patients co-infected with HIV and HCV (ANRS CO13 HEPAVIH): Early findings, 2006-2010. BMC Infectious Diseases, 10: 303doi:10.1186/1471-2334-10-303, 2010 (click here for access to article text).
Source
Management of Hepatitis B: A longitudinal national survey - impact of the Canadian Hepatitis B Consensus Guidelines
Original Articles
The Canadian Journal of Gastroenterology
September 2010, Volume 24 Issue 9: 537-542
P Marotta, K Lucas
BACKGROUND: The Canadian Association for the Study of the Liver, and The Association of Medical Microbiology and Infectious Diseases Canada, jointly developed the Canadian Chronic Hepatitis B (HBV) Consensus Guidelines to assist practitioners involved in the management of this complex disease. These guidelines were published in The Canadian Journal of Gastroenterology in June 2007 and distributed to all Canadian gastroenterologists and hepatologists.
OBJECTIVE: To assess the degree to which Canadian specialist physicians were able to incorporate the recommendations from the Canadian HBV Consensus Guidelines into their daily practice.
METHODS: A 30 min telephone survey probing the management strategies of 80 key HBV specialists was completed on three occasions, eight months apart, to longitudinally assess the impact of the Canadian HBV Consensus Guidelines on the management of HBV. The questionnaire detailed HBV practice patterns, the impact of the Canadian HBV Consensus Guidelines on clinical practice and HBV management.
RESULTS: The majority of specialists incorporated many of the published recommendations outlined in the Canadian HBV Consensus Guidelines into their daily practice for patients with HBV. However, because public drug coverage is a major hurdle in the management of HBV, patients are provided markedly different HBV treatments depending on whether they have public or private drug insurance coverage.
CONCLUSIONS: The management of HBV is growing in complexity and continues to evolve rapidly. The Canadian HBV Consensus Guidelines have served as a valuable tool for many physicians in the management of HBV. However, effective treatment algorithms continue to be rendered irrelevant by restrictive drug coverage issues. Coverage for effective therapies and, therefore, management of HBV, differs widely across Canada depending on therapy reimbursement criteria rather than patient characteristics.
Source
The Canadian Journal of Gastroenterology
September 2010, Volume 24 Issue 9: 537-542
P Marotta, K Lucas
BACKGROUND: The Canadian Association for the Study of the Liver, and The Association of Medical Microbiology and Infectious Diseases Canada, jointly developed the Canadian Chronic Hepatitis B (HBV) Consensus Guidelines to assist practitioners involved in the management of this complex disease. These guidelines were published in The Canadian Journal of Gastroenterology in June 2007 and distributed to all Canadian gastroenterologists and hepatologists.
OBJECTIVE: To assess the degree to which Canadian specialist physicians were able to incorporate the recommendations from the Canadian HBV Consensus Guidelines into their daily practice.
METHODS: A 30 min telephone survey probing the management strategies of 80 key HBV specialists was completed on three occasions, eight months apart, to longitudinally assess the impact of the Canadian HBV Consensus Guidelines on the management of HBV. The questionnaire detailed HBV practice patterns, the impact of the Canadian HBV Consensus Guidelines on clinical practice and HBV management.
RESULTS: The majority of specialists incorporated many of the published recommendations outlined in the Canadian HBV Consensus Guidelines into their daily practice for patients with HBV. However, because public drug coverage is a major hurdle in the management of HBV, patients are provided markedly different HBV treatments depending on whether they have public or private drug insurance coverage.
CONCLUSIONS: The management of HBV is growing in complexity and continues to evolve rapidly. The Canadian HBV Consensus Guidelines have served as a valuable tool for many physicians in the management of HBV. However, effective treatment algorithms continue to be rendered irrelevant by restrictive drug coverage issues. Coverage for effective therapies and, therefore, management of HBV, differs widely across Canada depending on therapy reimbursement criteria rather than patient characteristics.
Source
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