-Outlines Phase 2 Clinical Development Plan-
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Idera Pharmaceuticals, Inc. (Nasdaq: IDRA) announced today preliminary data from a 4-week dose-ranging Phase 1 clinical trial of IMO-2125 in combination with ribavirin in 60 treatment-naïve patients with genotype 1 chronic hepatitis C virus (HCV) infection. In the trial, treatment with IMO-2125 in combination with ribavirin was well tolerated and achieved substantial decline in virus levels at two days after the first dose of IMO-2125 and after four weeks of treatment. IMO-2125 is a Toll-like Receptor 9 (TLR9) agonist which stimulates production of natural interferons and other antiviral cytokines
"In this study, IMO-2125 plus ribavirin was well tolerated with no treatment-related discontinuations, and demonstrated substantial antiviral activity," said Robert Arbeit, M.D., Vice President of Clinical Development at Idera. "We believe that IMO-2125 may provide an alternative immune modulatory component to pegylated interferons in the anticipated HCV therapy combinations using direct-acting antivirals. In this treatment scenario, effective stimulation of the host immune system through TLR activation could minimize the risk of viral breakthrough.”
"Based on the overall data from this trial and our Phase 1 clinical trial of IMO-2125 in null-responder HCV patients, our next step in clinical development will be a 12-week Phase 2 trial of IMO-2125 in combination with ribavirin in treatment-naïve HCV patients,” said Sudhir Agrawal, D.Phil., Chairman and Chief Executive Officer at Idera. “We expect that the objectives of the Phase 2 study will be to determine optimal dosing, provide longer-term safety data and generate additional antiviral activity data in support of the future clinical development of IMO-2125.”
IMO-2125 Phase 1 Clinical Trial in Treatment-naïve Genotype 1 HCV Patients
Study Design:
In this Phase 1 clinical trial, treatment-naïve genotype 1 HCV patients received IMO-2125 by subcutaneous injection over four weeks in combination with daily oral administration of standard weight-based doses of ribavirin in one of four regimens of 12 patients each. The four regimens of IMO-2125 were 0.08, 0.16, and 0.32 mg/kg once weekly and 0.16 mg/kg twice weekly. In addition, 12 patients received current standard of care treatment (Pegasys® plus ribavirin).
Study Results:
Safety
• Treatment with IMO-2125 in combination with ribavirin was well tolerated at all dose levels for four weeks of treatment, with no treatment-related serious adverse events and no treatment discontinuations.
• The most common adverse events observed in the IMO-2125 regimens were flu-like symptoms and injection site reactions.
• Of the 12 patients receiving the standard of care therapy in this trial, neutropenia requiring intervention occurred in two patients and platelet counts dropped below the normal range during the treatment period in seven patients. None of the 48 patients receiving IMO-2125 had neutropenia requiring intervention, and four of the 48 IMO-2125 patients had platelet counts drop below the normal range during the treatment period.
Antiviral Activity
• IMO-2125 induced substantial declines in viral levels at two days after the first dose at all dose levels.
• At the mid-week evaluation in the fourth week of treatment, mean viral load reductions with the three higher-dose IMO-2125 regimens ranged from -2.0 to -3.4 log10. Patients who received Pegasys® plus ribavirin achieved a mean viral load reduction of -3.8 log10 at the same timepoint.
• At the end of the fourth week of treatment, mean viral load reductions with the three higher-dose IMO-2125 regimens ranged from -0.6 to -2.4 log10. The mean viral load reduction for patients treated with Pegasys® plus ribavirin at the end of the fourth week of treatment was -3.4 log10.
• The initial dose level in this Phase 1 safety trial, 0.08 mg/kg/week, produced minimal changes in viral load although liver enzyme decreases were observed.
• Liver enzymes (AST/ALT) decreased during the treatment period and were within the normal range by the end of the fourth week of treatment in the majority of IMO-2125-treated patients.
• There was unequal distribution among the treatment groups of patients with poor prognostic factors at baseline, including CT or TT IL28B genotype, IP-10 values >600 pg/mL, and older age.
The Company plans to present detailed results of this study at a scientific meeting in 2011.
Planned Phase 2 Clinical Trial
In the planned 12-week Phase 2 randomized clinical trial, patients will be stratified for IL28B genotype (CC vs. CT/TT) and will receive either IMO-2125 plus ribavirin or Pegasys® plus ribavirin. The Company plans for recruitment of this clinical trial to start in the first quarter of 2011, pending regulatory concurrence. The Company expects that the objective of this clinical trial will be to provide the basis for subsequent clinical development of IMO-2125 as an alternative to pegylated-interferon in triple combination therapy with ribavirin and a direct-acting antiviral.
IMO-2125 Monotherapy Phase 1 Clinical Trial in Null-Responder HCV Patients
IMO-2125 has also been evaluated in a Phase 1 clinical trial in 51 null-responder HCV patients; 41 patients received IMO-2125 monotherapy at one of five dose levels and 10 patients received placebo once per week for four weeks. Interim safety, antiviral activity and mechanism of action data were presented for the once-weekly dosing regimens in April 2010 at the Annual Meeting of the European Association for the Study of the Liver and complete data were presented in October 2010 at the Annual Meeting of the American Association for the Study of Liver Diseases.
Seven patients were enrolled in an additional cohort to evaluate twice-weekly dosing of IMO-2125 at 0.16 mg/kg/dose. Consistent with the patients’ null-responder status, 6 of 7 patients had CT or TT IL28B genotype. There were no treatment-related serious adverse events or discontinuations. As previously observed, the most common adverse events were injection site reactions and flu-like symptoms. Three patients in this cohort achieved greater than 1 log10 reduction, ranging from -1.9 to -3.5 log10, in viral load at least once during the treatment period. One of the patients with CT genotype achieved HCV viral levels at the lower limit of quantification (100 copies/mL) at Day 29, four days after the last IMO-2125 dose.
“We are pleased that the results of our Phase 1 clinical trials have shown that IMO-2125 stimulates the immune system in a manner consistent with the intended TLR9 agonist mechanism of action, and that this biological activity has led to reductions in HCV viral load,” said Tim Sullivan, Vice President of Development Programs and Alliance Management at Idera. “IMO-2125 was designed using our chemistry-based approach to optimize the activity of TLR-targeted drug candidates.”
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 has been evaluated 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 and in a Phase 1 clinical trial in treatment-naïve HCV patients in combination with ribavirin for 4 weeks.
About Idera Pharmaceuticals, Inc.
Idera Pharmaceuticals is developing drug candidates that act by modulating immune responses through specific Toll-like Receptors (TLRs). TLRs, a family of immune system receptors and the immune system’s first line of defense, recognize pathogens and initiate an immune response. Idera’s DNA and RNA chemistry expertise has generated a pipeline of compounds designed to interact with specific TLRs for a broad range of diseases. Through its internal pipeline and collaborative alliances, Idera has established a portfolio of TLR-targeted therapeutic candidates for infectious diseases, autoimmune and inflammatory diseases, cancer, and respiratory diseases, and for use as vaccine adjuvants. 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 and clinical studies such as the studies 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 September 30, 2010, which important factors are incorporated herein by reference. Idera disclaims any intention or obligation to update any forward-looking statements.
Pegasys® is a registered trademark of F. Hoffmann-La Roche Company.
Contacts
Idera Pharmaceuticals, Inc.
Teri Dahlman, 617-679-5519
tdahlman@iderapharma.com
or
MacDougall Biomedical Communications
Chris Erdman, 781-235-3060
cerdman@macbiocom.com
Source
December 21, 2010
Rapid Virological Response Is the Most Important Predictor of Sustained Virological Response Across Genotypes in Patients with Chronic Hepatitis C Virus Infection
J Hepatol. 2010 Nov 23. [Epub ahead of print]
Fried MW, Hadziyannis SJ, Shiffman ML, Messinger D, Zeuzem S.
University of North Carolina, Chapel Hill, USA.
Abstract
The probability of response to peginterferon and ribavirin is associated with numerous host and virological factors. Attainment of a rapid virological response (RVR), defined as undetectable HCV RNA at week 4 during treatment with peginterferon and ribavirin, is highly predictive of sustained virological response (SVR). The aim of the present study was to determine the relative importance of the kinetics of antiviral response compared to baseline host and virological factors for predicting SVR.
METHODS: A retrospective analysis of 1,383 patients, encompassing genotypes 1-4, treated with peginterferon alfa-2a and ribavirin was performed. Baseline characteristics were compared across HCV genotypes and pretreatment factors associated with RVR were identified. The relative significance of RVR compared to other baseline factors for predicting SVR was analyzed by multiple logistic regression analysis.
RESULTS: RVR was achieved by 16% of patients with genotype 1 and 71% and 60% of those with genotype 2 and 3, respectively. Among patients who achieved RVR, the rate of SVR was high across all genotypes and ranged from 88% to 100% (genotypes 1-4). Baseline factors predictive of RVR included genotype, younger age, lower initial viral load, higher ALT ratio, absence of advanced fibrosis, and younger age. Notably, the presence of RVR generated the highest odds ratio (5.47, 95% confidence interval 3.97-7.52) for predicting SVR in multiple logistic regression analysis of these factors.
CONCLUSIONS: Attainment of RVR varies by genotype and is associated with several baseline factors. Patients who achieve RVR have the highest rates of SVR, regardless of genotype. These findings have important implications for predicting and managing response-guided combination antiviral therapies.
Copyright © 2010. Published by Elsevier B.V.
PMID: 21145856 [PubMed - as supplied by publisher]
Source
Fried MW, Hadziyannis SJ, Shiffman ML, Messinger D, Zeuzem S.
University of North Carolina, Chapel Hill, USA.
Abstract
The probability of response to peginterferon and ribavirin is associated with numerous host and virological factors. Attainment of a rapid virological response (RVR), defined as undetectable HCV RNA at week 4 during treatment with peginterferon and ribavirin, is highly predictive of sustained virological response (SVR). The aim of the present study was to determine the relative importance of the kinetics of antiviral response compared to baseline host and virological factors for predicting SVR.
METHODS: A retrospective analysis of 1,383 patients, encompassing genotypes 1-4, treated with peginterferon alfa-2a and ribavirin was performed. Baseline characteristics were compared across HCV genotypes and pretreatment factors associated with RVR were identified. The relative significance of RVR compared to other baseline factors for predicting SVR was analyzed by multiple logistic regression analysis.
RESULTS: RVR was achieved by 16% of patients with genotype 1 and 71% and 60% of those with genotype 2 and 3, respectively. Among patients who achieved RVR, the rate of SVR was high across all genotypes and ranged from 88% to 100% (genotypes 1-4). Baseline factors predictive of RVR included genotype, younger age, lower initial viral load, higher ALT ratio, absence of advanced fibrosis, and younger age. Notably, the presence of RVR generated the highest odds ratio (5.47, 95% confidence interval 3.97-7.52) for predicting SVR in multiple logistic regression analysis of these factors.
CONCLUSIONS: Attainment of RVR varies by genotype and is associated with several baseline factors. Patients who achieve RVR have the highest rates of SVR, regardless of genotype. These findings have important implications for predicting and managing response-guided combination antiviral therapies.
Copyright © 2010. Published by Elsevier B.V.
PMID: 21145856 [PubMed - as supplied by publisher]
Source
Vertex Provides Update to Ongoing Phase 2 Study Evaluating Combinations of Telaprevir and VX-222 for the Treatment of Hepatitis C
- Two-drug treatment arm of telaprevir and VX-222 alone discontinued
- Study continues with three arms, including all-oral combination of Vertex's lead protease and polymerase inhibitors with ribavirin
- Both of the four-drug treatment arms are fully enrolled; the majority of patients in these arms have reached 8 weeks or more of treatment
CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced a modification of its Phase 2 clinical trial evaluating 12-week, response-guided regimens of its lead investigational hepatitis C virus (HCV) protease inhibitor, telaprevir, in combination with its lead investigational HCV polymerase inhibitor, VX-222. The company has discontinued the second two-drug treatment arm of telaprevir and VX-222 alone as a result of meeting a pre-defined stopping rule related to viral breakthrough. This two-drug arm was designed to evaluate a 12-week combination regimen of VX-222 (400 mg) and telaprevir (1,125 mg) dosed twice daily without pegylated-interferon and ribavirin. The first two-drug arm was discontinued in October 2010 and was designed to evaluate a 12-week combination regimen of VX-222 (100 mg) and telaprevir (1,125 mg).
The study will continue as planned with three treatment arms. Two of the treatment arms are fully enrolled and are evaluating four-drug combinations of telaprevir (1,125 mg), VX-222 (400 mg or 100 mg), Pegasys® (pegylated-interferon alfa-2a) and Copegus® (ribavirin). The last patient was randomized and began treatment with a four-drug regimen in November 2010. There are patients in the four-drug treatment arms who have recently started treatment and have not yet reached week 8 of therapy. More than half of patients in the treatment arms have received eight weeks or more of treatment and approximately one third of patients are in weeks 10 through 12 of treatment. Some patients in this study have completed therapy. Interim data from both of the four-drug treatment arms are expected in the first quarter of 2011. In November 2010, Vertex announced the planned addition of a new three-drug treatment arm designed to evaluate the potential of an all-oral, interferon-free regimen of telaprevir (1,125 mg), VX-222 (400 mg) and ribavirin dosed twice daily. Enrollment in this new treatment arm is expected to begin in the first quarter of 2011.
"This trial has provided important information regarding telaprevir and VX-222-based combination regimens, and three of the five treatment arms are proceeding as planned," said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer for Vertex. "We are pleased with the progress of both four-drug treatment arms and look forward to the first quarter of 2011 when on-treatment data from these arms will become available and enrollment in the three-drug treatment arm is expected to begin."
About the Ongoing Phase 2 Trial of Telaprevir and VX-222
In August 2010, patients enrolled in this randomized, parallel-group, dose-ranging Phase 2 trial started receiving treatment. The primary endpoint of this trial is to assess safety and tolerability of 12-week, telaprevir/VX-222-based combination therapy in people with genotype 1 chronic hepatitis C. A secondary endpoint of this study is to assess on-treatment antiviral activity and the proportion of patients in each study arm who achieve a sustained viral response (SVR; defined as undetectable HCV RNA 24 weeks after the end of treatment). Patients who meet the response-guided criteria during treatment (undetectable HCV RNA at week 2 and week 8 of treatment) stop all therapy at week 12.
The planned addition of the three-drug treatment arm to the study took into account an initial review of adverse events among people treated with telaprevir/VX-222 combination regimens in this study. Enrollment in this new study arm is expected to begin in the first quarter of 2011 pending completion of institutional review board (IRB) approvals and consultations with regulatory agencies. A sixth and final arm may be added to the trial per protocol based on data from the study expected in the first quarter of 2011.
European and United States Regulatory Submissions for Telaprevir
On December 17, 2010, Janssen-Cilag International NV announced the submission of a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for telaprevir in combination with pegylated-interferon and ribavirin for the treatment of people with genotype 1 hepatitis C. Additionally, Janssen announced that the EMA has accepted telaprevir for accelerated assessment, which is granted to new medicines of major public health interest. In November 2010, Vertex announced it has completed the submission of a New Drug Application to the U.S. Food and Drug Administration for telaprevir in combination with pegylated-interferon and ribavirin for the treatment of people with genotype 1 hepatitis C. The submission included a request for six-month Priority Review, which can be granted for several reasons, including if the medicine is considered a major advance in treatment.
Telaprevir is being developed by Vertex Pharmaceuticals in collaboration with Tibotec BVBA and Mitsubishi Tanabe Pharma. Vertex has rights to commercialize telaprevir in North America. Through its affiliate, Janssen, Tibotec has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries.
About Telaprevir and VX-222
Telaprevir is an investigational, oral inhibitor of HCV protease, an enzyme essential for viral replication. VX-222 is an investigational, oral, non-nucleoside inhibitor of HCV NS5B polymerase. Vertex added VX-222 to its development pipeline as part of the acquisition of ViroChem Pharma Inc. in March 2009. Vertex retains worldwide commercial rights to VX-222.
About Hepatitis C
Hepatitis C is a serious liver disease caused by the hepatitis C virus, which is spread through direct contact with the blood of infected people and ultimately affects the liver.2 Up to 3.9 million people in the United States have chronic hepatitis C and 75% of those infected are unaware of their infection.3 The majority of people with hepatitis C were born between 1946 and 1964, accounting for two of every three people with chronic hepatitis C.11 Chronic hepatitis C can lead to serious and life-threatening liver problems, including liver damage, cirrhosis, liver failure or liver cancer.2 Though many people with hepatitis C may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.2
Approximately 60 percent of genotype 1 patients who undergo an initial 48-week regimen with pegylated-interferon and ribavirin, the currently approved medicines, do not achieve SVR, 4,5,6 or viral cure.1 If treatment is not successful and a person does not achieve a viral cure, they remain at an increased risk for progressive liver disease.7,8,9,10,11 In the United States, hepatitis C is the leading cause of liver transplantations and is reported to contribute to 4,600 to 12,000 deaths annually.8 By 2029, total annual medical costs in the U.S. for people with hepatitis C are expected to more than double, from $30 billion in 2009 to approximately $85 billion.11
Additional resources for media are available at: http://investors.vrtx.com/press.cfm.
About Vertex
Vertex Pharmaceuticals Incorporated is a global biotechnology company committed to the discovery and development of breakthrough small molecule drugs for serious diseases. The Company's strategy is to commercialize its products both independently and in collaboration with other pharmaceutical companies. Vertex's product pipeline is focused on viral diseases, cystic fibrosis, inflammation, autoimmune diseases, epilepsy, cancer and pain.
Vertex co-discovered the HIV protease inhibitor, Lexiva, with GlaxoSmithKline.
Lexiva is a registered trademark of the GlaxoSmithKline group of companies.
PEGASYS® and COPEGUS® are registered trademarks of Hoffman-La Roche.
References:
1 Ghany MG, Strader DB, Thomas DL, Seeff, LB. Diagnosis, management and treatment of hepatitis C; An update. Hepatology. 2009; 49 (4): 1-40.
2 Centers for Disease Control and Prevention. Hepatitis C Fact Sheet: CDC Viral Hepatitis. Available at: http://www.cdc.gov/hepatitis/HCV/PDFs/HepCGeneralFactSheet.pdf. Accessed May 25, 2010.
3 Institute of Medicine of the National Academies. Hepatitis and liver cancer: a national strategy for prevention and control of hepatitis B and C. Colvin HM and Mitchell AE, ed. http://www.iom.edu/Reports/2010/Hepatitis-and-Liver-Cancer-A-National-Strategy-for-Prevention-and-Control-of-Hepatitis-B-and-C.aspx. Updated January 11, 2010. Accessed May 25, 2010.
4 Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001; 358: 958-965.
5 Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002; 347: 975-982.
6 McHutchison JG, Lawitz EJ, Shiffman ML, et al; IDEAL Study Team. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med. 2009;361:580-593.
7 Morgan TR, Ghany MG, Kim HY, Snow KK, Lindsay K, Lok AS. Outcome of sustained virological responders and non-responders in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial. Hepatology. 2008;50(Suppl 4):357A (Abstract 115).
8 Davis GL, Alter MJ, El-Serag H, Poynard T, Jennings LW. Aging of hepatitis C virus (HCV)-infected persons in the United States: A multiple cohort model of HCV prevalence and disease progression. Gastroenterology. 2010;138:513-521.
9 Volk MI, Tocco R, Saini S, Lok, ASF. Public health impact of antiviral therapy for hepatitis C in the United States. Hepatology. 2009;50(6):1750-1755.
10 Veldt BJ, Heathcote J, Wedmeyer H. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Annals of Internal Medicine. 2007; 147: 677-684.
11 Pyenson B, Fitch K, Iwasaki K. Consequences of hepatitis C virus (HCV): Costs of a baby boomer epidemic of liver disease. http://www.natap.org/2009/HCV/051809_01.htm. Updated May 2009. This report was commissioned by Vertex Pharmaceuticals, Inc.
12 Picchio G, et al. Discrepancies between definitions of null response to treatment with peginterferon alfa-2a and ribavirin: Implications for new HCV drug development. [poster 289]. In: Program and Abstracts of the 2010 International Liver Conference by the European Association for the Study of Liver Disease. . Athens, Greece: April 2010.
13 United States Food and Drug Administration. Chronic hepatitis C virus infection: developing direct-acting antiviral agents for treatment. http://www.federalregister.gov/articles/2010/09/14/2010-22806/draft-guidance-for-industry-on-chronic-hepatitis-c-virus-infection-developing-directacting-antiviral. Updated September 14, 2010. Accessed September 14, 2010.
Special Note Regarding Forward-looking Statements
This press release contains forward-looking statements including statements regarding (i) that the study will continue with three treatment arms, including an all-oral, interferon-free regimen of telaprevir, VX-222 (400 mg) and ribavirin; (ii) the expectation that interim data from both of the four-drug treatment arms are expected in the first quarter of 2011; (iii) Vertex looking forward to on-treatment data that is expected to become available from these arms in the first quarter of 2011; (iv) the plan to evaluate a 12-week combination of the three oral therapies — VX-222, telaprevir and ribavirin — dosed twice daily within a response-guided regimen; (v) the expectation that the additional three-drug treatment arm announced in November 2010 will begin patient enrollment in the first quarter of 2011, pending completion of IRB approvals and consultation with regulatory agencies; and (vi) the possibility that a sixth and final arm may be added to the trial. While Vertex believes the forward-looking statements contained in this press release are accurate, these statements are subject to risks and uncertainties that could cause actual outcomes to vary materially from the outcomes referenced in the forward-looking statements. These risks and uncertainties include, among other things, the risks that efforts to develop telaprevir and VX-222 separately or in combination may not proceed due to technical, scientific, commercial, financial or other reasons, that clinical trials may not proceed as planned, that additional clinical trials of telaprevir and VX-222 will not reflect the results obtained to date, that an adverse event profile for telaprevir or VX-222 could be revealed in further nonclinical or clinical studies that could put further development of telaprevir or VX-222 in jeopardy or adversely impact their therapeutic value, and other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through the Company's website at http://www.vrtx.com/. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.
(VRTX-GEN)
Vertex Pharmaceuticals Incorporated
Media: 617-444-6992
Amy Pasqua
Dawn Kalmar
Zachry Barber
or
Investors:
Michael Partridge, 617-444-6108
Lora Pike, 617-444-6755
Matthew Osborne, 617-444-6057
Source: Vertex Pharmaceuticals Incorporated
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- Study continues with three arms, including all-oral combination of Vertex's lead protease and polymerase inhibitors with ribavirin
- Both of the four-drug treatment arms are fully enrolled; the majority of patients in these arms have reached 8 weeks or more of treatment
CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced a modification of its Phase 2 clinical trial evaluating 12-week, response-guided regimens of its lead investigational hepatitis C virus (HCV) protease inhibitor, telaprevir, in combination with its lead investigational HCV polymerase inhibitor, VX-222. The company has discontinued the second two-drug treatment arm of telaprevir and VX-222 alone as a result of meeting a pre-defined stopping rule related to viral breakthrough. This two-drug arm was designed to evaluate a 12-week combination regimen of VX-222 (400 mg) and telaprevir (1,125 mg) dosed twice daily without pegylated-interferon and ribavirin. The first two-drug arm was discontinued in October 2010 and was designed to evaluate a 12-week combination regimen of VX-222 (100 mg) and telaprevir (1,125 mg).
The study will continue as planned with three treatment arms. Two of the treatment arms are fully enrolled and are evaluating four-drug combinations of telaprevir (1,125 mg), VX-222 (400 mg or 100 mg), Pegasys® (pegylated-interferon alfa-2a) and Copegus® (ribavirin). The last patient was randomized and began treatment with a four-drug regimen in November 2010. There are patients in the four-drug treatment arms who have recently started treatment and have not yet reached week 8 of therapy. More than half of patients in the treatment arms have received eight weeks or more of treatment and approximately one third of patients are in weeks 10 through 12 of treatment. Some patients in this study have completed therapy. Interim data from both of the four-drug treatment arms are expected in the first quarter of 2011. In November 2010, Vertex announced the planned addition of a new three-drug treatment arm designed to evaluate the potential of an all-oral, interferon-free regimen of telaprevir (1,125 mg), VX-222 (400 mg) and ribavirin dosed twice daily. Enrollment in this new treatment arm is expected to begin in the first quarter of 2011.
"This trial has provided important information regarding telaprevir and VX-222-based combination regimens, and three of the five treatment arms are proceeding as planned," said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer for Vertex. "We are pleased with the progress of both four-drug treatment arms and look forward to the first quarter of 2011 when on-treatment data from these arms will become available and enrollment in the three-drug treatment arm is expected to begin."
About the Ongoing Phase 2 Trial of Telaprevir and VX-222
In August 2010, patients enrolled in this randomized, parallel-group, dose-ranging Phase 2 trial started receiving treatment. The primary endpoint of this trial is to assess safety and tolerability of 12-week, telaprevir/VX-222-based combination therapy in people with genotype 1 chronic hepatitis C. A secondary endpoint of this study is to assess on-treatment antiviral activity and the proportion of patients in each study arm who achieve a sustained viral response (SVR; defined as undetectable HCV RNA 24 weeks after the end of treatment). Patients who meet the response-guided criteria during treatment (undetectable HCV RNA at week 2 and week 8 of treatment) stop all therapy at week 12.
The planned addition of the three-drug treatment arm to the study took into account an initial review of adverse events among people treated with telaprevir/VX-222 combination regimens in this study. Enrollment in this new study arm is expected to begin in the first quarter of 2011 pending completion of institutional review board (IRB) approvals and consultations with regulatory agencies. A sixth and final arm may be added to the trial per protocol based on data from the study expected in the first quarter of 2011.
European and United States Regulatory Submissions for Telaprevir
On December 17, 2010, Janssen-Cilag International NV announced the submission of a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for telaprevir in combination with pegylated-interferon and ribavirin for the treatment of people with genotype 1 hepatitis C. Additionally, Janssen announced that the EMA has accepted telaprevir for accelerated assessment, which is granted to new medicines of major public health interest. In November 2010, Vertex announced it has completed the submission of a New Drug Application to the U.S. Food and Drug Administration for telaprevir in combination with pegylated-interferon and ribavirin for the treatment of people with genotype 1 hepatitis C. The submission included a request for six-month Priority Review, which can be granted for several reasons, including if the medicine is considered a major advance in treatment.
Telaprevir is being developed by Vertex Pharmaceuticals in collaboration with Tibotec BVBA and Mitsubishi Tanabe Pharma. Vertex has rights to commercialize telaprevir in North America. Through its affiliate, Janssen, Tibotec has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries.
About Telaprevir and VX-222
Telaprevir is an investigational, oral inhibitor of HCV protease, an enzyme essential for viral replication. VX-222 is an investigational, oral, non-nucleoside inhibitor of HCV NS5B polymerase. Vertex added VX-222 to its development pipeline as part of the acquisition of ViroChem Pharma Inc. in March 2009. Vertex retains worldwide commercial rights to VX-222.
About Hepatitis C
Hepatitis C is a serious liver disease caused by the hepatitis C virus, which is spread through direct contact with the blood of infected people and ultimately affects the liver.2 Up to 3.9 million people in the United States have chronic hepatitis C and 75% of those infected are unaware of their infection.3 The majority of people with hepatitis C were born between 1946 and 1964, accounting for two of every three people with chronic hepatitis C.11 Chronic hepatitis C can lead to serious and life-threatening liver problems, including liver damage, cirrhosis, liver failure or liver cancer.2 Though many people with hepatitis C may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.2
Approximately 60 percent of genotype 1 patients who undergo an initial 48-week regimen with pegylated-interferon and ribavirin, the currently approved medicines, do not achieve SVR, 4,5,6 or viral cure.1 If treatment is not successful and a person does not achieve a viral cure, they remain at an increased risk for progressive liver disease.7,8,9,10,11 In the United States, hepatitis C is the leading cause of liver transplantations and is reported to contribute to 4,600 to 12,000 deaths annually.8 By 2029, total annual medical costs in the U.S. for people with hepatitis C are expected to more than double, from $30 billion in 2009 to approximately $85 billion.11
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About Vertex
Vertex Pharmaceuticals Incorporated is a global biotechnology company committed to the discovery and development of breakthrough small molecule drugs for serious diseases. The Company's strategy is to commercialize its products both independently and in collaboration with other pharmaceutical companies. Vertex's product pipeline is focused on viral diseases, cystic fibrosis, inflammation, autoimmune diseases, epilepsy, cancer and pain.
Vertex co-discovered the HIV protease inhibitor, Lexiva, with GlaxoSmithKline.
Lexiva is a registered trademark of the GlaxoSmithKline group of companies.
PEGASYS® and COPEGUS® are registered trademarks of Hoffman-La Roche.
References:
1 Ghany MG, Strader DB, Thomas DL, Seeff, LB. Diagnosis, management and treatment of hepatitis C; An update. Hepatology. 2009; 49 (4): 1-40.
2 Centers for Disease Control and Prevention. Hepatitis C Fact Sheet: CDC Viral Hepatitis. Available at: http://www.cdc.gov/hepatitis/HCV/PDFs/HepCGeneralFactSheet.pdf. Accessed May 25, 2010.
3 Institute of Medicine of the National Academies. Hepatitis and liver cancer: a national strategy for prevention and control of hepatitis B and C. Colvin HM and Mitchell AE, ed. http://www.iom.edu/Reports/2010/Hepatitis-and-Liver-Cancer-A-National-Strategy-for-Prevention-and-Control-of-Hepatitis-B-and-C.aspx. Updated January 11, 2010. Accessed May 25, 2010.
4 Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001; 358: 958-965.
5 Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002; 347: 975-982.
6 McHutchison JG, Lawitz EJ, Shiffman ML, et al; IDEAL Study Team. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med. 2009;361:580-593.
7 Morgan TR, Ghany MG, Kim HY, Snow KK, Lindsay K, Lok AS. Outcome of sustained virological responders and non-responders in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial. Hepatology. 2008;50(Suppl 4):357A (Abstract 115).
8 Davis GL, Alter MJ, El-Serag H, Poynard T, Jennings LW. Aging of hepatitis C virus (HCV)-infected persons in the United States: A multiple cohort model of HCV prevalence and disease progression. Gastroenterology. 2010;138:513-521.
9 Volk MI, Tocco R, Saini S, Lok, ASF. Public health impact of antiviral therapy for hepatitis C in the United States. Hepatology. 2009;50(6):1750-1755.
10 Veldt BJ, Heathcote J, Wedmeyer H. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Annals of Internal Medicine. 2007; 147: 677-684.
11 Pyenson B, Fitch K, Iwasaki K. Consequences of hepatitis C virus (HCV): Costs of a baby boomer epidemic of liver disease. http://www.natap.org/2009/HCV/051809_01.htm. Updated May 2009. This report was commissioned by Vertex Pharmaceuticals, Inc.
12 Picchio G, et al. Discrepancies between definitions of null response to treatment with peginterferon alfa-2a and ribavirin: Implications for new HCV drug development. [poster 289]. In: Program and Abstracts of the 2010 International Liver Conference by the European Association for the Study of Liver Disease. . Athens, Greece: April 2010.
13 United States Food and Drug Administration. Chronic hepatitis C virus infection: developing direct-acting antiviral agents for treatment. http://www.federalregister.gov/articles/2010/09/14/2010-22806/draft-guidance-for-industry-on-chronic-hepatitis-c-virus-infection-developing-directacting-antiviral. Updated September 14, 2010. Accessed September 14, 2010.
Special Note Regarding Forward-looking Statements
This press release contains forward-looking statements including statements regarding (i) that the study will continue with three treatment arms, including an all-oral, interferon-free regimen of telaprevir, VX-222 (400 mg) and ribavirin; (ii) the expectation that interim data from both of the four-drug treatment arms are expected in the first quarter of 2011; (iii) Vertex looking forward to on-treatment data that is expected to become available from these arms in the first quarter of 2011; (iv) the plan to evaluate a 12-week combination of the three oral therapies — VX-222, telaprevir and ribavirin — dosed twice daily within a response-guided regimen; (v) the expectation that the additional three-drug treatment arm announced in November 2010 will begin patient enrollment in the first quarter of 2011, pending completion of IRB approvals and consultation with regulatory agencies; and (vi) the possibility that a sixth and final arm may be added to the trial. While Vertex believes the forward-looking statements contained in this press release are accurate, these statements are subject to risks and uncertainties that could cause actual outcomes to vary materially from the outcomes referenced in the forward-looking statements. These risks and uncertainties include, among other things, the risks that efforts to develop telaprevir and VX-222 separately or in combination may not proceed due to technical, scientific, commercial, financial or other reasons, that clinical trials may not proceed as planned, that additional clinical trials of telaprevir and VX-222 will not reflect the results obtained to date, that an adverse event profile for telaprevir or VX-222 could be revealed in further nonclinical or clinical studies that could put further development of telaprevir or VX-222 in jeopardy or adversely impact their therapeutic value, and other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through the Company's website at http://www.vrtx.com/. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.
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Vertex Pharmaceuticals Incorporated
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or
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Source: Vertex Pharmaceuticals Incorporated
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