By Bill Berkrot
NEW YORK
Sat Oct 30, 2010 2:12pm BST
NEW YORK (Reuters) - A closer look at data from a late stage trial of Vertex Pharmaceuticals Inc's eagerly anticipated hepatitis C drug telaprevir showed impressive cure rates for black patients and for patients with advanced liver disease.
In the Phase III study known as Advance, 62 percent of black patients who received telaprevir achieved sustained viral response (SVR), which is considered tantamount to a cure. That compared with just a 25 percent cure rate from the current standard drugs of pegylated interferon and ribavirin.
"If you look at that treatment difference and then you look at the difference in the overall population, in fact the benefit relatively speaking is even greater," Robert Kauffman, Vertex's chief medical officer, said in a telephone interview.
"Obviously, from an absolute point of view it's still a little bit lesser response," he said.
The study's overall cure rates -- 75 percent for telaprevir in combination with the current standard drugs versus 44 percent for the standard drugs alone -- was previously released. But full details of the trial were being presented for the first time at the American Association for the Study of Liver Diseases meeting in Boston.
Breaking out an analysis of black patients in the trial was significant because of the greater prevalence of hepatitis C and historically lower cure rates for that population.
"African Americans bare a large proportion of the burden of hepatitis C in the United States" compared with Caucasians and the overall general population, Kauffman said.
According to data compiled from 1999 to 2002, one in seven African American men between the ages of 50 and 59 in the United States is living with hepatitis C.
Telaprevir, from a new class of antiviral drugs, is widely expected to be approved by U.S. regulators next year. Vertex plans to complete its application seeking approval this year.
Excitement has been high over the drug, and a similar experimental medicine being developed by Merck & Co, because they have demonstrated significantly higher cure rates than current drugs and the potential to cut treatment duration in half for many patients.
Cutting treatment duration from the current 48 weeks is a huge advantage as the current drugs, which must still be taken with the new medicines, can cause debilitating flu-like symptoms that cause many patients to discontinue treatment or avoid it altogether. It is believed that thousands of patients with hepatitis C have been putting off treatment to await the new, more effective medicines.
In the Advance study, 58 percent of patients who received telaprevir met the criteria for a 24-week treatment duration. That criteria called for levels of the virus in the blood to fall to undetectable levels after four and 12 weeks of treatment.
A separate study demonstrated no additional benefit from extending telaprevir treatment to the full 48 weeks in patients who met the criteria for shorter duration treatment.
A further sub-group analysis of the Advance data showed that telaprevir led to a 62 percent cure rate in hepatitis C patients with advanced liver fibrosis or cirrhosis compared with a 33 percent SVR rate on standard drugs. Patients with those conditions, which can lead to liver cancer or need for a transplant, are also traditionally more difficult to treat than the overall hepatitis C population.
"In our Phase III program, starting people with 12 weeks of telaprevir-based combination therapy resulted in significant improvements in viral cure rates, regardless of race, extent of liver damage or experience with prior treatment," Kauffman said.
(Reporting by Bill Berkrot; Editing by Bernard Orr)
Source
October 30, 2010
Achieving Sustained Viral Response for Patients with Recurrent Hepatitis C After Transplantation is Key for Long-Term Outcomes
Presented: Sunday, October 31, 8:45 am Eastern Time
BOSTON, Oct. 30 /PRNewswire/ -- Researchers from the University of Bari, Italy, concluded that treating patients after transplantation with antiviral therapy creates a sustained viral response (SVR) and protects them from liver-related deaths. The purpose of this study was to determine the long-term clinical outcomes of patients posttransplant who underwent antiviral therapy for recurrent hepatitis C virus (HCV) infection of the liver graft.
The use in clinical practice of antiviral therapy for HCV recurrence after liver transplantation is still controversial. Some favor antiviral therapy while data coming from meta-analysis of published studies do not recommend treatment in view of the frequent adverse effects and the lack of clinical benefit.
Maria Rendina, MD, on behalf of the AISF RECOLT-C Group, examined the records from 12 liver transplant centers in Italy over a 20-year period, and showed data on SVR and long-term clinical outcomes for a large posttransplantation patient population.
SVR was achieved in 35 percent of the 448 patients whose records were included in this study. Researchers noted that patients who achieved SVR received grafts from younger donors, received longer treatment duration and cumulative dose of interferon, and had a lower drop-out rate and lower incidence of diabetes; however there were no differences in immunosuppressive strategy for these patients.
Of the 134 patients who died since transplantation, 73 percent of those deaths were HCV related – and only one of those patients was able to achieve SVR. After univariate and multivariate analysis to correct for other variables, researchers demonstrated that patients with recurrent HCV who were unable to achieve SVR were at a high risk for liver-related deaths.
According to Dr. Rendina: "The results of the study are important as these data could have an impact on patient care: HCV viral eradication significantly protects patients from liver-related death and, therefore, must be strongly pursued. When asked about the future of research in this area, Dr. Rendina said, "Data from the AISF RECOLT-C Group provide a direction for further randomized clinical trials aimed at exploring various treatment options as well as the efficacy of new antivirals."
Abstract title:
SVR to antiviral therapy is highly protective against liver-related death in patients with HCV recurrence on the graft after liver transplantation (LT)
About the AASLD
AASLD is the leading medical organization for advancing the science and practice of hepatology. Founded by physicians in 1950, AASLD's vision is to prevent and cure liver diseases. This year's Liver Meeting®, held in Boston, Massachusetts, October 29-November 2, will bring together more than 7,500 researchers from 55 countries.
A pressroom will be available from October 30 at the annual meeting. For copies of abstracts and press releases, or to arrange for pre-conference research interviews contact Gregory Bologna at 703-299-9766. To pre-register, call Ann Haran at 703-299-9766.
Press releases and all abstracts are available online at http://www.aasld.org/.
Media Contact: Gregory Bologna
703-299-9766
gbologna@aasld.org
Press Room: October 30 – November 2, 2010
Hynes Convention Center, Room 208
Telephone: 617-954-3106
Researcher: Maria Rendina, MD
University of Bari, Italy
Email: mrendina@yahoo.com
Source
BOSTON, Oct. 30 /PRNewswire/ -- Researchers from the University of Bari, Italy, concluded that treating patients after transplantation with antiviral therapy creates a sustained viral response (SVR) and protects them from liver-related deaths. The purpose of this study was to determine the long-term clinical outcomes of patients posttransplant who underwent antiviral therapy for recurrent hepatitis C virus (HCV) infection of the liver graft.
The use in clinical practice of antiviral therapy for HCV recurrence after liver transplantation is still controversial. Some favor antiviral therapy while data coming from meta-analysis of published studies do not recommend treatment in view of the frequent adverse effects and the lack of clinical benefit.
Maria Rendina, MD, on behalf of the AISF RECOLT-C Group, examined the records from 12 liver transplant centers in Italy over a 20-year period, and showed data on SVR and long-term clinical outcomes for a large posttransplantation patient population.
SVR was achieved in 35 percent of the 448 patients whose records were included in this study. Researchers noted that patients who achieved SVR received grafts from younger donors, received longer treatment duration and cumulative dose of interferon, and had a lower drop-out rate and lower incidence of diabetes; however there were no differences in immunosuppressive strategy for these patients.
Of the 134 patients who died since transplantation, 73 percent of those deaths were HCV related – and only one of those patients was able to achieve SVR. After univariate and multivariate analysis to correct for other variables, researchers demonstrated that patients with recurrent HCV who were unable to achieve SVR were at a high risk for liver-related deaths.
According to Dr. Rendina: "The results of the study are important as these data could have an impact on patient care: HCV viral eradication significantly protects patients from liver-related death and, therefore, must be strongly pursued. When asked about the future of research in this area, Dr. Rendina said, "Data from the AISF RECOLT-C Group provide a direction for further randomized clinical trials aimed at exploring various treatment options as well as the efficacy of new antivirals."
Abstract title:
SVR to antiviral therapy is highly protective against liver-related death in patients with HCV recurrence on the graft after liver transplantation (LT)
About the AASLD
AASLD is the leading medical organization for advancing the science and practice of hepatology. Founded by physicians in 1950, AASLD's vision is to prevent and cure liver diseases. This year's Liver Meeting®, held in Boston, Massachusetts, October 29-November 2, will bring together more than 7,500 researchers from 55 countries.
A pressroom will be available from October 30 at the annual meeting. For copies of abstracts and press releases, or to arrange for pre-conference research interviews contact Gregory Bologna at 703-299-9766. To pre-register, call Ann Haran at 703-299-9766.
Press releases and all abstracts are available online at http://www.aasld.org/.
Media Contact: Gregory Bologna
703-299-9766
gbologna@aasld.org
Press Room: October 30 – November 2, 2010
Hynes Convention Center, Room 208
Telephone: 617-954-3106
Researcher: Maria Rendina, MD
University of Bari, Italy
Email: mrendina@yahoo.com
Source
Boehringer Ingelheim Oral Hepatitis C Protease Inhibitor and Polymerase Inhibitor Combination Shows Rapid Viral Response without Use of Pegylated Interferon
BusinessWire · Saturday, Oct. 30, 2010
Boehringer Ingelheim announced results from a Phase Ib study, SOUND-C1, that showed the combination of two oral hepatitis C virus (HCV) compounds, the protease inhibitor BI 201335 and the polymerase inhibitor BI 207127, with ribavirin reduced viral load to the lower limit of quantifiable levels in HCV treatment-naïve patients. The regimen did not include interferon through the first 28 days of treatment. These data are being presented at the American Association for the Study of Liver Diseases (AASLD) 2010 Liver Meeting in Boston, MA.
(Poster LB-7) New protease-polymerase inhibitor combination resulted in 73-100%rapid virological responses without pegylated interferon
In this randomised open-label trial, 32 treatment-naïve genotype-1 HCV patients received a combination of BI 207127 in either 400mg or 600mg doses three times a day (TID) with BI 201335 120mg once daily (QD) together with ribavirin (RBV) (1000/1200mg daily in two doses) for 28 days. All patients had a rapid and sharp decline in HCV viral load during the first two days, followed by a slower second phase decline. In the lower and higher dose groups, 73 and 100% of patients achieved a rapid virological response (i.e. had a HCV RNA below thelower limit of quantification after 4 weeks of treatment). One patient experienced a viral breakthrough (increase by >1 LOG10 from nadir during treatment) and one other experienced a 0.7 LOG10 increase in viral load. Both patients were in the lower dose group of BI 207127 and were patients with a high baseline viral load. On day 29, all patients were switched to treatment with BI 201335 and PegIFN/RBV for an additional 44 weeks per the defined study protocol, and will be followed to evaluate sustained virological response.
“These early data suggest that there is the potential for the combination of oral anti-HCV therapies to reduce the viral load in a more tolerable, interferon-sparing regimen. The current standard-of-care, PegIFN/RBV, is challenging for HCV patients due to side effects that impact treatment adherence and has suboptimal response rates,” said Stefan Zeuzem, MD, Chief of the Department of Medicine and Professor of Medicine at the Johann Wolfgang Goethe University Hospital in Frankfurt, Germany and lead investigator of the study. “An interferon-sparing regimen could provide an important treatment option for patients with chronic hepatitis C.”
The PegIFN sparing treatment was well tolerated. Investigators reported that the most common adverse events observed in the study were mild gastro-intestinal effects (diarrhea, nausea, vomiting), rash or photosensitivity. Laboratory parameters did not indicate any relevant changes from baseline, except for a continuous drop in amino alanine transferase (ALT) in all patients, a decrease of hemoglobin (median -1.7 and -2.6 g/dL) and an increase of unconjugated bilirubin (median +9.8 and +11.5 umol/L) similar to reported results from earlier BI 201335 trials. There were no serious or severe adverse events and no discontinuations due to adverse events reported in the study during treatment with BI 207127 and BI 201335. A phase IIb trial testing different dose regimens of this combination with longer durations is planned to evaluate sustained virological response rates.
Additional studies to be presented at AASLD
• Virological response and safety of 4 weeks treatment with the protease inhibitor BI 201335 combined with 48 weeks of peginterferon alpha 2a and ribavirin for treatment of HCV GT-1 patients who failed peginterferon / ribavirin
(Poster 804. T. Berg, et al. Sun, October 31 - 8:00 AM. Hynes: Exhibit Hall C)
• Genotypic and phenotypic analysis of the NS5B polymerase region from viral isolates of HCV chronically infected patients treated with BI 207127 for 5-days monotherapy.
(Poster 1862. L. Lagace, et al. Tue, November 2 - 7:00 AM. Hynes: Exhibit Hall C)
• The Liver Kp Corrected Inhibitory Quotient (LCIQ): A pharmacokinetic-pharmacodynamic model for direct-acting HCV antivirals
(Poster 1866. J. Duan, et al. Tue, 2 November 2 – 7:00 AM. Hynes: Exhibit Hall C)
About Hepatitis C Virus (HCV)
HCV is an infectious disease of the liver and is a leading cause of chronic liver disease and liver transplant. The number of individuals chronically infected with HCV globally has been estimated at 170 million, with 3–4 million new infections occurring each year. Only about 20–45% of patients clear the virus in the acute phase. Of the remaining chronically infected patients, 20% will develop cirrhosis within a mean of 20 years. The mortality rate after cirrhosis has developed is 2-5% per year. End-stage liver disease due to HCV infection currently represents the major indication for liver transplantation in the Western world.
About Boehringer Ingelheim in Virology
Boehringer Ingelheim has more than 6,900 scientists working in cross disciplinary teams within our global R&D network in six large therapeutic areas, including virology. In addition to its ongoing research program for HCV, Boehringer Ingelheim has a long-standing history in virology drug development, including compounds for the treatment of HIV (VIRAMUNE® (nevirapine) tablets/oral solution, the first approved HIV non-nucleoside reverse transcriptase inhibitor (NNRTI) and Aptivus®, an HIV protease inhibitor). The company has a well established research centre in Laval, Canada, dedicated to virology research since the early 1990’s, and is committed to developing new therapies for virological diseases with a high unmet medical need.
Boehringer Ingelheim in Hepatitis C Virus (HCV)
BI 201335 is an investigational oral HCV NS3/4A protease inhibitor, discovered from Boehringer Ingelheim’s own research and development, which has completed clinical trials through Phase IIb (SILEN-C studies). This Phase II program supports the investigation of BI 201335 in Phase III trials. BI 207127 is an NS5B RNA-dependent polymerase inhibitor that has completed Phase I clinical trials. Planning is currently underway to begin Phase II trials of BI 207127 with BI 201335 in interferon-sparing regimens both with and without ribavirin.
Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 142 affiliates in 50 countries and more than 41,500 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.
In 2009, Boehringer Ingelheim posted net sales of 12.7 billion euro (US $17.7 billion) while spending 21% of net sales in its largest business segment, Prescription Medicines, on research and development.
For more information, please visit http://www.boehringer-ingelheim.com/
Contacts
Julia Meyer-Kleinmann
Director Corporate Communications
Boehringer Ingelheim GmbH
55216 Ingelheim/Germany
Phone: + 49 - 6132 – 77 8271
Fax: + 49 - 6132 – 77 70 77
E-mail: press@boehringer-ingelheim.com
Source
Boehringer Ingelheim announced results from a Phase Ib study, SOUND-C1, that showed the combination of two oral hepatitis C virus (HCV) compounds, the protease inhibitor BI 201335 and the polymerase inhibitor BI 207127, with ribavirin reduced viral load to the lower limit of quantifiable levels in HCV treatment-naïve patients. The regimen did not include interferon through the first 28 days of treatment. These data are being presented at the American Association for the Study of Liver Diseases (AASLD) 2010 Liver Meeting in Boston, MA.
(Poster LB-7) New protease-polymerase inhibitor combination resulted in 73-100%rapid virological responses without pegylated interferon
In this randomised open-label trial, 32 treatment-naïve genotype-1 HCV patients received a combination of BI 207127 in either 400mg or 600mg doses three times a day (TID) with BI 201335 120mg once daily (QD) together with ribavirin (RBV) (1000/1200mg daily in two doses) for 28 days. All patients had a rapid and sharp decline in HCV viral load during the first two days, followed by a slower second phase decline. In the lower and higher dose groups, 73 and 100% of patients achieved a rapid virological response (i.e. had a HCV RNA below thelower limit of quantification after 4 weeks of treatment). One patient experienced a viral breakthrough (increase by >1 LOG10 from nadir during treatment) and one other experienced a 0.7 LOG10 increase in viral load. Both patients were in the lower dose group of BI 207127 and were patients with a high baseline viral load. On day 29, all patients were switched to treatment with BI 201335 and PegIFN/RBV for an additional 44 weeks per the defined study protocol, and will be followed to evaluate sustained virological response.
“These early data suggest that there is the potential for the combination of oral anti-HCV therapies to reduce the viral load in a more tolerable, interferon-sparing regimen. The current standard-of-care, PegIFN/RBV, is challenging for HCV patients due to side effects that impact treatment adherence and has suboptimal response rates,” said Stefan Zeuzem, MD, Chief of the Department of Medicine and Professor of Medicine at the Johann Wolfgang Goethe University Hospital in Frankfurt, Germany and lead investigator of the study. “An interferon-sparing regimen could provide an important treatment option for patients with chronic hepatitis C.”
The PegIFN sparing treatment was well tolerated. Investigators reported that the most common adverse events observed in the study were mild gastro-intestinal effects (diarrhea, nausea, vomiting), rash or photosensitivity. Laboratory parameters did not indicate any relevant changes from baseline, except for a continuous drop in amino alanine transferase (ALT) in all patients, a decrease of hemoglobin (median -1.7 and -2.6 g/dL) and an increase of unconjugated bilirubin (median +9.8 and +11.5 umol/L) similar to reported results from earlier BI 201335 trials. There were no serious or severe adverse events and no discontinuations due to adverse events reported in the study during treatment with BI 207127 and BI 201335. A phase IIb trial testing different dose regimens of this combination with longer durations is planned to evaluate sustained virological response rates.
Additional studies to be presented at AASLD
• Virological response and safety of 4 weeks treatment with the protease inhibitor BI 201335 combined with 48 weeks of peginterferon alpha 2a and ribavirin for treatment of HCV GT-1 patients who failed peginterferon / ribavirin
(Poster 804. T. Berg, et al. Sun, October 31 - 8:00 AM. Hynes: Exhibit Hall C)
• Genotypic and phenotypic analysis of the NS5B polymerase region from viral isolates of HCV chronically infected patients treated with BI 207127 for 5-days monotherapy.
(Poster 1862. L. Lagace, et al. Tue, November 2 - 7:00 AM. Hynes: Exhibit Hall C)
• The Liver Kp Corrected Inhibitory Quotient (LCIQ): A pharmacokinetic-pharmacodynamic model for direct-acting HCV antivirals
(Poster 1866. J. Duan, et al. Tue, 2 November 2 – 7:00 AM. Hynes: Exhibit Hall C)
About Hepatitis C Virus (HCV)
HCV is an infectious disease of the liver and is a leading cause of chronic liver disease and liver transplant. The number of individuals chronically infected with HCV globally has been estimated at 170 million, with 3–4 million new infections occurring each year. Only about 20–45% of patients clear the virus in the acute phase. Of the remaining chronically infected patients, 20% will develop cirrhosis within a mean of 20 years. The mortality rate after cirrhosis has developed is 2-5% per year. End-stage liver disease due to HCV infection currently represents the major indication for liver transplantation in the Western world.
About Boehringer Ingelheim in Virology
Boehringer Ingelheim has more than 6,900 scientists working in cross disciplinary teams within our global R&D network in six large therapeutic areas, including virology. In addition to its ongoing research program for HCV, Boehringer Ingelheim has a long-standing history in virology drug development, including compounds for the treatment of HIV (VIRAMUNE® (nevirapine) tablets/oral solution, the first approved HIV non-nucleoside reverse transcriptase inhibitor (NNRTI) and Aptivus®, an HIV protease inhibitor). The company has a well established research centre in Laval, Canada, dedicated to virology research since the early 1990’s, and is committed to developing new therapies for virological diseases with a high unmet medical need.
Boehringer Ingelheim in Hepatitis C Virus (HCV)
BI 201335 is an investigational oral HCV NS3/4A protease inhibitor, discovered from Boehringer Ingelheim’s own research and development, which has completed clinical trials through Phase IIb (SILEN-C studies). This Phase II program supports the investigation of BI 201335 in Phase III trials. BI 207127 is an NS5B RNA-dependent polymerase inhibitor that has completed Phase I clinical trials. Planning is currently underway to begin Phase II trials of BI 207127 with BI 201335 in interferon-sparing regimens both with and without ribavirin.
Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 142 affiliates in 50 countries and more than 41,500 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.
In 2009, Boehringer Ingelheim posted net sales of 12.7 billion euro (US $17.7 billion) while spending 21% of net sales in its largest business segment, Prescription Medicines, on research and development.
For more information, please visit http://www.boehringer-ingelheim.com/
Contacts
Julia Meyer-Kleinmann
Director Corporate Communications
Boehringer Ingelheim GmbH
55216 Ingelheim/Germany
Phone: + 49 - 6132 – 77 8271
Fax: + 49 - 6132 – 77 70 77
E-mail: press@boehringer-ingelheim.com
Source
Salix Pharmaceuticals Previews Data Slated for Presentation at 61st Annual Meeting of the American Association for the Study of Liver Diseases
Oct. 30, 2010, 9:00 a.m. EDT
BOSTON, Oct 30, 2010 (BUSINESS WIRE) -- Salix Pharmaceuticals, Inc. /quotes/comstock/15*!slxp/quotes/nls/slxp (SLXP 37.83, +0.41, +1.10%) today announced that the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2010) will be an important venue for ongoing discussion of hepatic encephalopathy, or HE. Numerous posters and oral presentations provide insight regarding HE's burden on patients, caregivers and the healthcare system; the earlier identification and diagnosis of HE; the growing recognition of the importance of aggressive management of HE; and the use of XIFAXAN(R) (rifaximin) 550 mg for the reduction in risk of overt HE recurrence.
"In the last decade, HE-related hospitalizations have more than doubled. Today, an estimated one third to one half of all hospitalizations in cirrhotic patients are partially or wholly attributable to hepatic encephalopathy," stated Bill Forbes, Executive Vice President, Research and Development and Chief Development Officer, Salix, "Hepatic encephalopathy signifies a poor prognosis with one-year and three-year mortality rates of 58 percent and 77 percent, respectively, after presentation of the first episode of acute HE. The introduction of XIFAXAN 550 mg, the first new therapy approved for HE in 30 years, is providing physicians a much-needed therapy to manage their patients and to help patients break the cycle of relapse. Additionally, the availability of this tolerable and efficacious treatment for overt HE has re-energized the HE research community and challenged physicians to more aggressively approach HE therapy with the intention of improving treatment success and long-term outcomes."
Rifaximin-Related Presentations at AASLD
Oral Presentation #24: Leise et al. "Impact of Rifaximin Treatment on Survival in Patients with End-stage Liver Disease." Sunday, Oct. 31, 2010, 1:00 - 2:30 p.m., Hynes, Room 312
This analysis compared the long term effect of rifaximin by comparing survival in HE patients receiving rifaximin (long-term open label trial) versus patients awaiting liver transplantation (Organ Procurement and Transplant network).
Oral Presentation #19: Vlachogiannakos et al. "Long-term Administration of Rifaximin Improves the Prognosis of Patients with Alcohol-related Decompensated Cirrhosis: A Case-control study." Sunday, Oct. 31, 2010, 1:00 - 2:30 pm, Hynes, Room 312
This study evaluated the effect of intestinal decontamination with rifaximin (1200 mg for 4 weeks) on the long-term prognosis of 23 patients with alcohol-related decompensated cirrhosis and ascites. Five-year cumulative probability of survival data were obtained.
Oral Presentation #22: Bajaj et al. "Rifaximin Improves Driving Simulator Performance in Minimal Hepatic Encephalopathy: A Double-blind, Placebo-controlled, Prospective Randomized Trial." Sunday, Oct. 31, 2010, 1:00 - 2:30 p.m., Hynes, Room 312
A total of 42 MHE patients, diagnosed using a battery of five tests of cognitive function (CB) and without overt HE, participated in the eight-week trial. Patients initially underwent a baseline evaluation of driving and navigation simulation (outcomes were speeding tickets, collisions and illegal turns), Quality of Life with Sickness Impact Profile (SIP, which includes physical/psycho-social scores), ammonia and model for end-stage liver disease (MELD) score, in addition to the CB. Patients were randomized to receive XIFAXAN 550 mg or placebo twice-daily (BID) (n=21 in each group). All evaluations were repeated at the eight-week visit. The primary outcomes were proportion improved in speeding, illegal turns and collisions; secondary outcomes were proportion improved in mean CB Zscores and SIP scores. In addition to being presented at AASLD, this study was recently published in Gastroenterology.
Poster #1192: Krag et. al. "Systematic Review and Meta-analyses of Randomised Trials on Ammonia lowering Regimens for Hepatic Encephalopathy." Monday, Nov. 1, 2010, 8:00 a.m. - 5:30 p.m., Hynes, Exhibit Hall C.
These meta-analyses of 21 randomized trials evaluated the effects of ammonia lowering interventions in the management of hepatic encephalopathy.
About Hepatic Encephalopathy
Hepatic encephalopathy (HE) is a disorder caused by chronic liver failure resulting in cognitive, psychiatric and motor impairments.The condition encompasses a wide spectrum of often reversible neuropsychiatric abnormalities caused by the inability of the liver to remove toxic products in the gut from most notably ammonia-producing bacteria. When toxins reach the central nervous system, this condition can result in symptoms ranging in severity from mild cerebral function deficits to coma. The disorder is characterized by disruption in sleep patterns, changes in personality and intellectual capacity, high blood ammonia levels, altered neuromuscular activity and electroencephalogram (EEG) abnormalities.
About XIFAXAN(R) (rifaximin) 550 mg tablets
Important Safety Information
XIFAXAN 550 mg is indicated for reduction in risk of overt hepatic encephalopathy (HE) recurrence in patients greater-than or equal to 18 years of age. In the trials of XIFAXAN for HE, 91 percent of the patients were using lactulose concomitantly. XIFAXAN has not been studied in patients with MELD scores greater than 25, and only 8.6 percent of patients in the controlled trial had MELD scores over 19. There is increased systemic exposure in patients with more severe hepatic dysfunction. Therefore, caution should be exercised when administering XIFAXAN to patients with severe hepatic impairment (Child-Pugh C).
XIFAXAN is contraindicated in patients with a hypersensitivity to rifaximin, any of the rifamycin antimicrobial agents, or any of the components in XIFAXAN. Hypersensitivity reactions have included exfoliative dermatitis, angioneurotic edema and anaphylaxis.
Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including XIFAXAN and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon which may lead to overgrowth of C. difficile. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued.
The most common adverse reactions occurring in greater than eight percent of patients in the clinical study were edema peripheral (15 percent), nausea (14 percent), dizziness (13 percent), fatigue (12 percent), ascites (11 percent), muscle spasms (nine percent), pruritus (nine percent) and abdominal pain (nine percent).
About XIFAXAN(R) (rifaximin) 200 mg tablets
Rifaximin is a gut-selective antibiotic with negligible systemic absorption and broad-spectrum activity in vitro against both Gram-positive and Gram-negative pathogens. Rifaximin has a similar tolerability profile to that of placebo.
Rifaximin tablets 200 mg, which Salix markets in the U.S. under the trade name XIFAXAN(R) (rifaximin) tablets 200 mg, currently is approved for the treatment of patients, 12 years of age or older, with travelers' diarrhea (TD) caused by non--invasive strains of Escherichia coli. XIFAXAN should not be used in patients with diarrhea complicated by fever or blood in the stool or diarrhea due to pathogens other than Escherichia coli. XIFAXAN should be discontinued if diarrhea symptoms get worse or persist more than 24--48 hours, and alternative antibiotic therapy should be considered. In clinical trials, XIFAXAN was generally well-tolerated. The most common side effects (versus placebo) were flatulence 11.3 percent (versus 19.7 percent), headache 9.7 percent (versus 9.2 percent), abdominal pain 7.2 percent (versus 10.1 percent) and rectal tenesmus 7.2 percent (versus 8.8 percent).
Rifaximin has been used in Italy for 24 years and is approved in 33 countries. Salix acquired rights to market rifaximin in North America from Alfa Wassermann S.p.A. in Bologna, Italy. Alfa Wassermann markets rifaximin in Italy under the trade name Normix(R).
About Salix Pharmaceuticals
Salix Pharmaceuticals, Ltd., headquartered in Raleigh, NC, develops and markets prescription pharmaceutical products for the treatment of gastrointestinal diseases. Salix's strategy is to in-license late-stage or marketed proprietary therapeutic drugs, complete with any required development and regulatory submission of these products, and market them through the Company's gastroenterology specialty sales and marketing team.
Salix also markets MOVIPREP(R) (PEG 3350, sodium sulfate, sodium chloride, potassium chloride, sodium ascorbate and ascorbic acid for oral solution), OSMOPREP(R) (sodium phosphate monobasic monohydrate, USP and sodium phosphate dibasic anhydrous, USP) Tablets, VISICOL(R) (sodium phosphate monobasic monohydrate, USP, and sodium phosphate dibasic anhydrous, USP) Tablets, APRISO(TM) (mesalamine) extended-release capsules 0.375 g., METOZOLV(R) ODT (metoclopramide HCl), PEPCID(R) (famotidine) for Oral Suspension, Oral Suspension DIURIL(R) (Chlorothiazide), AZASAN(R) Azathioprine Tablets, USP, 75/100 mg, ANUSOL-HC(R) 2.5% (Hydrocortisone Cream, USP), ANUSOL-HC(R) 25 mg Suppository (Hydrocortisone Acetate), PROCTOCORT(R) Cream (Hydrocortisone Cream, USP) 1% and PROCTOCORT(R) Suppository (Hydrocortisone Acetate Rectal Suppositories) 30 mg. Crofelemer, budesonide foam and rifaximin for additional indications are under development.
For full prescribing information and important safety information on Salix products, including BOXED WARNINGS for VISICOL, OSMOPREP and METOZOLV ODT, please visit www.salix.com where the Company promptly posts press releases, SEC filings and other important information, or contact the Company at 919-862-1000.
For more information, please visit our Website at http://www.salix.com/ or contact the Company at 919-862-1000. Information on our Website is not incorporated into our SEC filings.
Please Note: The materials provided herein contain projections and other forward-looking statements regarding future events. Such statements are just predictions and are subject to risks and uncertainties that could cause the actual events or results to differ materially. These risks and uncertainties include, among others: the unpredictable nature of the duration and results of regulatory review of new drug applications; market acceptance for approved products; generic and other competition; the possible impairment of, or inability to obtain, intellectual property rights and the costs of obtaining such rights from third parties; our need to return to profitability; and the need to acquire new products. The reader is referred to the documents that the Company files from time to time with the Securities and Exchange Commission.
SOURCE: Salix Pharmaceuticals, Inc.
Sonoco
Adam C. Derbyshire, Executive Vice President and Chief Financial Officer or
G. Michael Freeman, Associate Vice President, Investor Relations and
Corporate Communications, 919-862-1000
Source
BOSTON, Oct 30, 2010 (BUSINESS WIRE) -- Salix Pharmaceuticals, Inc. /quotes/comstock/15*!slxp/quotes/nls/slxp (SLXP 37.83, +0.41, +1.10%) today announced that the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2010) will be an important venue for ongoing discussion of hepatic encephalopathy, or HE. Numerous posters and oral presentations provide insight regarding HE's burden on patients, caregivers and the healthcare system; the earlier identification and diagnosis of HE; the growing recognition of the importance of aggressive management of HE; and the use of XIFAXAN(R) (rifaximin) 550 mg for the reduction in risk of overt HE recurrence.
"In the last decade, HE-related hospitalizations have more than doubled. Today, an estimated one third to one half of all hospitalizations in cirrhotic patients are partially or wholly attributable to hepatic encephalopathy," stated Bill Forbes, Executive Vice President, Research and Development and Chief Development Officer, Salix, "Hepatic encephalopathy signifies a poor prognosis with one-year and three-year mortality rates of 58 percent and 77 percent, respectively, after presentation of the first episode of acute HE. The introduction of XIFAXAN 550 mg, the first new therapy approved for HE in 30 years, is providing physicians a much-needed therapy to manage their patients and to help patients break the cycle of relapse. Additionally, the availability of this tolerable and efficacious treatment for overt HE has re-energized the HE research community and challenged physicians to more aggressively approach HE therapy with the intention of improving treatment success and long-term outcomes."
Rifaximin-Related Presentations at AASLD
Oral Presentation #24: Leise et al. "Impact of Rifaximin Treatment on Survival in Patients with End-stage Liver Disease." Sunday, Oct. 31, 2010, 1:00 - 2:30 p.m., Hynes, Room 312
This analysis compared the long term effect of rifaximin by comparing survival in HE patients receiving rifaximin (long-term open label trial) versus patients awaiting liver transplantation (Organ Procurement and Transplant network).
Oral Presentation #19: Vlachogiannakos et al. "Long-term Administration of Rifaximin Improves the Prognosis of Patients with Alcohol-related Decompensated Cirrhosis: A Case-control study." Sunday, Oct. 31, 2010, 1:00 - 2:30 pm, Hynes, Room 312
This study evaluated the effect of intestinal decontamination with rifaximin (1200 mg for 4 weeks) on the long-term prognosis of 23 patients with alcohol-related decompensated cirrhosis and ascites. Five-year cumulative probability of survival data were obtained.
Oral Presentation #22: Bajaj et al. "Rifaximin Improves Driving Simulator Performance in Minimal Hepatic Encephalopathy: A Double-blind, Placebo-controlled, Prospective Randomized Trial." Sunday, Oct. 31, 2010, 1:00 - 2:30 p.m., Hynes, Room 312
A total of 42 MHE patients, diagnosed using a battery of five tests of cognitive function (CB) and without overt HE, participated in the eight-week trial. Patients initially underwent a baseline evaluation of driving and navigation simulation (outcomes were speeding tickets, collisions and illegal turns), Quality of Life with Sickness Impact Profile (SIP, which includes physical/psycho-social scores), ammonia and model for end-stage liver disease (MELD) score, in addition to the CB. Patients were randomized to receive XIFAXAN 550 mg or placebo twice-daily (BID) (n=21 in each group). All evaluations were repeated at the eight-week visit. The primary outcomes were proportion improved in speeding, illegal turns and collisions; secondary outcomes were proportion improved in mean CB Zscores and SIP scores. In addition to being presented at AASLD, this study was recently published in Gastroenterology.
Poster #1192: Krag et. al. "Systematic Review and Meta-analyses of Randomised Trials on Ammonia lowering Regimens for Hepatic Encephalopathy." Monday, Nov. 1, 2010, 8:00 a.m. - 5:30 p.m., Hynes, Exhibit Hall C.
These meta-analyses of 21 randomized trials evaluated the effects of ammonia lowering interventions in the management of hepatic encephalopathy.
About Hepatic Encephalopathy
Hepatic encephalopathy (HE) is a disorder caused by chronic liver failure resulting in cognitive, psychiatric and motor impairments.The condition encompasses a wide spectrum of often reversible neuropsychiatric abnormalities caused by the inability of the liver to remove toxic products in the gut from most notably ammonia-producing bacteria. When toxins reach the central nervous system, this condition can result in symptoms ranging in severity from mild cerebral function deficits to coma. The disorder is characterized by disruption in sleep patterns, changes in personality and intellectual capacity, high blood ammonia levels, altered neuromuscular activity and electroencephalogram (EEG) abnormalities.
About XIFAXAN(R) (rifaximin) 550 mg tablets
Important Safety Information
XIFAXAN 550 mg is indicated for reduction in risk of overt hepatic encephalopathy (HE) recurrence in patients greater-than or equal to 18 years of age. In the trials of XIFAXAN for HE, 91 percent of the patients were using lactulose concomitantly. XIFAXAN has not been studied in patients with MELD scores greater than 25, and only 8.6 percent of patients in the controlled trial had MELD scores over 19. There is increased systemic exposure in patients with more severe hepatic dysfunction. Therefore, caution should be exercised when administering XIFAXAN to patients with severe hepatic impairment (Child-Pugh C).
XIFAXAN is contraindicated in patients with a hypersensitivity to rifaximin, any of the rifamycin antimicrobial agents, or any of the components in XIFAXAN. Hypersensitivity reactions have included exfoliative dermatitis, angioneurotic edema and anaphylaxis.
Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including XIFAXAN and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon which may lead to overgrowth of C. difficile. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued.
The most common adverse reactions occurring in greater than eight percent of patients in the clinical study were edema peripheral (15 percent), nausea (14 percent), dizziness (13 percent), fatigue (12 percent), ascites (11 percent), muscle spasms (nine percent), pruritus (nine percent) and abdominal pain (nine percent).
About XIFAXAN(R) (rifaximin) 200 mg tablets
Rifaximin is a gut-selective antibiotic with negligible systemic absorption and broad-spectrum activity in vitro against both Gram-positive and Gram-negative pathogens. Rifaximin has a similar tolerability profile to that of placebo.
Rifaximin tablets 200 mg, which Salix markets in the U.S. under the trade name XIFAXAN(R) (rifaximin) tablets 200 mg, currently is approved for the treatment of patients, 12 years of age or older, with travelers' diarrhea (TD) caused by non--invasive strains of Escherichia coli. XIFAXAN should not be used in patients with diarrhea complicated by fever or blood in the stool or diarrhea due to pathogens other than Escherichia coli. XIFAXAN should be discontinued if diarrhea symptoms get worse or persist more than 24--48 hours, and alternative antibiotic therapy should be considered. In clinical trials, XIFAXAN was generally well-tolerated. The most common side effects (versus placebo) were flatulence 11.3 percent (versus 19.7 percent), headache 9.7 percent (versus 9.2 percent), abdominal pain 7.2 percent (versus 10.1 percent) and rectal tenesmus 7.2 percent (versus 8.8 percent).
Rifaximin has been used in Italy for 24 years and is approved in 33 countries. Salix acquired rights to market rifaximin in North America from Alfa Wassermann S.p.A. in Bologna, Italy. Alfa Wassermann markets rifaximin in Italy under the trade name Normix(R).
About Salix Pharmaceuticals
Salix Pharmaceuticals, Ltd., headquartered in Raleigh, NC, develops and markets prescription pharmaceutical products for the treatment of gastrointestinal diseases. Salix's strategy is to in-license late-stage or marketed proprietary therapeutic drugs, complete with any required development and regulatory submission of these products, and market them through the Company's gastroenterology specialty sales and marketing team.
Salix also markets MOVIPREP(R) (PEG 3350, sodium sulfate, sodium chloride, potassium chloride, sodium ascorbate and ascorbic acid for oral solution), OSMOPREP(R) (sodium phosphate monobasic monohydrate, USP and sodium phosphate dibasic anhydrous, USP) Tablets, VISICOL(R) (sodium phosphate monobasic monohydrate, USP, and sodium phosphate dibasic anhydrous, USP) Tablets, APRISO(TM) (mesalamine) extended-release capsules 0.375 g., METOZOLV(R) ODT (metoclopramide HCl), PEPCID(R) (famotidine) for Oral Suspension, Oral Suspension DIURIL(R) (Chlorothiazide), AZASAN(R) Azathioprine Tablets, USP, 75/100 mg, ANUSOL-HC(R) 2.5% (Hydrocortisone Cream, USP), ANUSOL-HC(R) 25 mg Suppository (Hydrocortisone Acetate), PROCTOCORT(R) Cream (Hydrocortisone Cream, USP) 1% and PROCTOCORT(R) Suppository (Hydrocortisone Acetate Rectal Suppositories) 30 mg. Crofelemer, budesonide foam and rifaximin for additional indications are under development.
For full prescribing information and important safety information on Salix products, including BOXED WARNINGS for VISICOL, OSMOPREP and METOZOLV ODT, please visit www.salix.com where the Company promptly posts press releases, SEC filings and other important information, or contact the Company at 919-862-1000.
For more information, please visit our Website at http://www.salix.com/ or contact the Company at 919-862-1000. Information on our Website is not incorporated into our SEC filings.
Please Note: The materials provided herein contain projections and other forward-looking statements regarding future events. Such statements are just predictions and are subject to risks and uncertainties that could cause the actual events or results to differ materially. These risks and uncertainties include, among others: the unpredictable nature of the duration and results of regulatory review of new drug applications; market acceptance for approved products; generic and other competition; the possible impairment of, or inability to obtain, intellectual property rights and the costs of obtaining such rights from third parties; our need to return to profitability; and the need to acquire new products. The reader is referred to the documents that the Company files from time to time with the Securities and Exchange Commission.
SOURCE: Salix Pharmaceuticals, Inc.
Sonoco
Adam C. Derbyshire, Executive Vice President and Chief Financial Officer or
G. Michael Freeman, Associate Vice President, Investor Relations and
Corporate Communications, 919-862-1000
Source
Race Affects Hepatitis C Recurrence After Liver Transplant: Study
Patients who receive organ from a white donor at higher risk, researchers find
Posted: October 30, 2010
SATURDAY, Oct. 30 (HealthDay News) -- Hepatitis C patients who receive a liver from a white donor have significantly more aggressive recurrent hepatitis than those who receive a liver from a black donor, researchers have found.
This is especially true for black patients who receive a liver from a white donor, the study authors noted.
Researchers from Henry Ford Hospital in Detroit looked at 165 hepatitis C patients who received a liver transplant at the hospital between 2000 and 2006. The patients were given a recurrent hepatitis C virus (HCV) score between 1 and 3.
The average recurrent HCV score for patients for each donor/recipient race combination was:
• White donor/white recipient: 1.54
• White donor/black recipient: 1.89
• Black donor/white recipient: 1.18
• Black donor/black recipient: 1.23
"The data suggests a graft from a white donor is potentially one more important variable in identifying patients at risk for more aggressive recurrent hepatitis after transplant and warrants further study," lead author Dr. Matthew Moeller, a gastroenterology fellow, said in a hospital news release.
The study findings were slated to be presented Oct. 29 at the annual meeting of the American Association for the Study of Liver Diseases, in Boston.
According to data from the United Network for Organ Sharing cited in the news release, there are almost 18,000 Americans on the waiting list for liver transplants.
More information
The American Academy of Family Physicians has more about hepatitis C
Source
Posted: October 30, 2010
SATURDAY, Oct. 30 (HealthDay News) -- Hepatitis C patients who receive a liver from a white donor have significantly more aggressive recurrent hepatitis than those who receive a liver from a black donor, researchers have found.
This is especially true for black patients who receive a liver from a white donor, the study authors noted.
Researchers from Henry Ford Hospital in Detroit looked at 165 hepatitis C patients who received a liver transplant at the hospital between 2000 and 2006. The patients were given a recurrent hepatitis C virus (HCV) score between 1 and 3.
The average recurrent HCV score for patients for each donor/recipient race combination was:
• White donor/white recipient: 1.54
• White donor/black recipient: 1.89
• Black donor/white recipient: 1.18
• Black donor/black recipient: 1.23
"The data suggests a graft from a white donor is potentially one more important variable in identifying patients at risk for more aggressive recurrent hepatitis after transplant and warrants further study," lead author Dr. Matthew Moeller, a gastroenterology fellow, said in a hospital news release.
The study findings were slated to be presented Oct. 29 at the annual meeting of the American Association for the Study of Liver Diseases, in Boston.
According to data from the United Network for Organ Sharing cited in the news release, there are almost 18,000 Americans on the waiting list for liver transplants.
More information
The American Academy of Family Physicians has more about hepatitis C
Source
Wake Forest scientists successfully grow 'miniature livers'
Updated Oct. 30, 2010 at 11:29 a.m.
By Local Tech Wire
WINSTON-SALEM, N.C. – Scientists at Wake Forest University have engineered what they call a “miniature” liver in a lab that functions like the human organ.
It’s the latest tissue breakthrough at the Institute for Regenerative Medicine, which in 2006 reported the growth and transplant of bladders into humans. Anthony Atala, MD, the director of the institute, is a leading pioneer in the field of regenerative science.
Researchers are reporting their findings Sunday at the American Association for the Study of Liver Diseases as well as in the journal Hepatology.
These miniature livers function “at least in a laboratory setting,” the university said. Researchers plan now to study whether the livers will work after being transplanted in an animal model.
The livers were grown from human liver cells and are 1 inch in diameter and weigh some 20 ounces, the university said. In order to perform successfully in humans, an engineered liver would have to weigh at least 1 pound, the scientists said.
The achievement could lead to breakthroughs in treatments of people with liver disease and other ailments.
“We are excited about the possibilities this research represents, but must stress that we’re at an early stage and many technical hurdles must be overcome before it could benefit patients,” said Shay Soker, a professor of regenerative medicine who is the project director, in a statement. “Not only must we learn how to grow billions of liver cells at one time in order to engineer livers large enough for patients, but we must determine whether these organs are safe to use in patients.”
The miniature livers were produced after animal livers were treated to remove all its cells in a process called decellularization that left what scientists called a “skeleton” support structure. Immature human liver cells and cells that line blood vessels were then added to the structure to the network of blood vessels left in the animal livers.
The skeleton and cells were then placed into a so-called bioreactor that provided nutrients and oxygen.
Institute researchers are working on 22 different kinds of cells and organs
Source
By Local Tech Wire
WINSTON-SALEM, N.C. – Scientists at Wake Forest University have engineered what they call a “miniature” liver in a lab that functions like the human organ.
It’s the latest tissue breakthrough at the Institute for Regenerative Medicine, which in 2006 reported the growth and transplant of bladders into humans. Anthony Atala, MD, the director of the institute, is a leading pioneer in the field of regenerative science.
Researchers are reporting their findings Sunday at the American Association for the Study of Liver Diseases as well as in the journal Hepatology.
These miniature livers function “at least in a laboratory setting,” the university said. Researchers plan now to study whether the livers will work after being transplanted in an animal model.
The livers were grown from human liver cells and are 1 inch in diameter and weigh some 20 ounces, the university said. In order to perform successfully in humans, an engineered liver would have to weigh at least 1 pound, the scientists said.
The achievement could lead to breakthroughs in treatments of people with liver disease and other ailments.
“We are excited about the possibilities this research represents, but must stress that we’re at an early stage and many technical hurdles must be overcome before it could benefit patients,” said Shay Soker, a professor of regenerative medicine who is the project director, in a statement. “Not only must we learn how to grow billions of liver cells at one time in order to engineer livers large enough for patients, but we must determine whether these organs are safe to use in patients.”
The miniature livers were produced after animal livers were treated to remove all its cells in a process called decellularization that left what scientists called a “skeleton” support structure. Immature human liver cells and cells that line blood vessels were then added to the structure to the network of blood vessels left in the animal livers.
The skeleton and cells were then placed into a so-called bioreactor that provided nutrients and oxygen.
Institute researchers are working on 22 different kinds of cells and organs
Source
Idera Pharmaceuticals Presents Phase 1 Data on IMO-2125 Demonstrating Induction of Broad Antiviral Immune Response in Null-Responder HCV Patients
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
Source
"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
Source
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
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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)
Source
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.
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