Interim data from ZENITH will be presented during a late-breaker poster session at The Liver Meeting®, the 62nd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), in San Francisco November 4-8, 2011.
Data from the four-drug treatment arms (C and D) of ZENITH were announced today and showed that, regardless of treatment duration, 90 percent of patients in the VX-222 (400mg) group had undetectable levels of hepatitis C virus in the blood 12 weeks after the end of treatment (sustained viral response 12, or SVR12). Fifty percent (15/30) of patients who received the combination regimen including VX-222 (400mg) were eligible for a total of 12 weeks of treatment and 93 percent (14/15) of them achieved a viral cure (sustained viral response, or SVR). For patients in the VX-222 (400mg) arm who received an additional 12 weeks of pegylated-interferon and ribavirin alone, 87 percent (13/15) had undetectable hepatitis C virus 12 weeks after treatment ended. Study results also showed that patients treated with the four-drug regimen experienced a rapid viral response; more than 85 percent had undetectable heptatitis C virus in the blood at week four of treatment. The most frequent adverse events (more then 20 percent) observed in the four-drug treatment arms were fatigue, nausea, diarrhea, anemia, pruritis (itchiness), insomnia and rash. Interim data from ZENITH will be presented during a late-breaker poster session at The Liver Meeting®, the 62nd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), in San Francisco November 4-8, 2011.
“More than 85 percent of patients in the four-drug treatment arms of ZENITH had undetectable hepatitis C virus at week 4 and, regardless of treatment duration, 90 percent of them cleared the hepatitis C virus,” said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer at Vertex. “Based on these interim results, Vertex began discussions with regulatory agencies about the regulatory path for this four-drug regimen, with the intent to initiate Phase 3 studies in a broad group of people with genotype 1 hepatitis C in the first quarter of 2012.”
“The potential to achieve high viral cure rates with just 12 weeks of therapy is an exciting prospect for the future of treatment,” said David R. Nelson, M.D., Professor of Medicine at the University of Florida College of Medicine, Director of the UF Clinical and Translational Science Institute and Principal Investigator of the trial.
Patients in Arms C and D of ZENITH were assigned to receive all four drugs for the first 12 weeks of treatment. People who had undetectable hepatitis C virus levels in the blood (HCV RNA) at weeks two and eight were eligible to stop all treatment at week 12. The remaining patients were assigned to receive pegylated-interferon and ribavirin alone for an additional 12 weeks for a total of 24 weeks of treatment. In this study, VX-222, INCIVEK and ribavirin were given twice daily (BID).
Arms A (n=18) and B (n=29) of ZENITH were designed to evaluate all-oral, two-drug combination regimens of VX-222 (100 mg or 400 mg) and INCIVEK (1,125 mg). There was significant initial antiviral activity in people who were treated with VX-222 (400 mg) and INCIVEK in Arms A and B. However, as previously announced, these treatment arms were discontinued due to a pre-defined stopping rule related to viral breakthrough.
Two additional treatment arms (E and F) were added to the study to evaluate a 12-week, three-drug, all-oral, interferon-free regimen of VX-222 (400 mg), INCIVEK and ribavirin. Arm E (n=23) is evaluating people with genotype 1b chronic hepatitis C and Arm F (n=23) is evaluating people with genotype 1a chronic hepatitis C. Vertex expects to provide end-of-treatment data from the all-oral arms of the study in early 2012.
*50 percent (15/30) had undetectable hepatitis C virus at weeks 2 and 8 and were eligible to stop all treatment at week 12. Two people in the VX-222 (400 mg) treatment arm discontinued treatment before week 12 and did not achieve SVR12.
**38 percent (11/29) had undetectable hepatitis C virus at weeks 2 and 8 and were eligible to stop all treatment at week 12. Four people in the VX-222 (100 mg) treatment arm discontinued treatment before week 12 and two of them achieved SVR12.
+One person in the 12-week VX-222 (400 mg) treatment arm relapsed.
++Two people in the 12-week VX-222 (100 mg) treatment arm relapsed.
In ZENITH, the amount of hepatitis C virus in the blood was measured by the Roche COBAS® Taqman HCV test with a limit of quantification of less then 25 IU/mL).
The most frequent adverse events (≥20 percent) observed in the four-drug treatment arms (C and D) were fatigue, nausea, diarrhea, anemia, pruritis (itchiness), insomnia and rash. The majority of events were mild or moderate. Severe events observed in at least two patients were neutropenia, hypomagnesemia and anemia. Three people in each study arm discontinued treatment before week 12 and one person in each arm discontinued treatment between weeks 12 and 24 while they were receiving pegylated-interferon and ribavirin alone. No patient discontinued treatment due to gastrointestinal symptoms or viral breakthrough.
About ZENITH
ZENITH is an ongoing Phase 2 study that initially enrolled 106 people with genotype 1 chronic hepatitis C and began with four treatment arms designed to evaluate multiple response-guided treatment regimens with VX-222, Vertex's lead polymerase inhibitor in development, in combination with INCIVEK, Pegasys® (pegylated-interferon alfa-2a) and Copegus® (ribavirin), three medicines approved to treat hepatitis C. The primary endpoint of the study is safety and tolerability. The secondary endpoint is on-treatment antiviral activity and the proportion of people in each treatment arm who achieve a sustained viral response.
Updates on Vertex’s Development Plans in Hepatitis C
Vertex has several studies planned and ongoing designed to evaluate a total of 12 weeks of treatment for people with genotype 1 chronic hepatitis C.
Four-drug “QUAD” Regimens
Based on the results from ZENITH announced today and previously announced data from other treatment arms of the ZENITH study, Vertex is in discussions with regulatory agencies about the regulatory path for the four-drug regimen, with the intent to start a Phase 3 study evaluating a total treatment duration of 12 weeks in people with genotype 1 chronic hepatitis C who are new to treatment or who relapsed after at least one prior course of treatment with pegylated-interferon and ribavirin alone.
Vertex is also in discussions with regulatory agencies regarding two additional studies designed to evaluate 24- and 48-week response-guided, four-drug regimens in patients who are new to treatment and also have cirrhosis (scarring of the liver) and, separately, those who have not responded (partial and null responders) to at least one prior course of treatment with pegylated-interferon and ribavirin alone.
Interferon-Free, 12-Week Regimens
Vertex expects to provide end-of-treatment data from the all-oral arms (E and F) of ZENITH study in early 2012. These study arms are evaluating a 12-week regimen of VX-222, INCIVEK and ribavirin. Dosing for all patients is expected to be complete in December 2011.
12-Week INCIVEK Combination Regimen for IL28B Patients
In October 2011, Vertex announced the start of the Phase 3b CONCISE study that is designed to evaluate 12 weeks of INCIVEK in combination with pegylated-interferon and ribavirin among people with genotype 1 chronic hepatitis C who have the ‘CC' variation near the IL28B gene.
About INCIVEK and VX-222
INCIVEK™ (telaprevir) tablets is an oral medicine that acts directly on the hepatitis C virus protease, an enzyme essential for viral replication. INCIVEK is the most prescribed direct-acting antiviral for the treatment of genotype 1 chronic hepatitis C and has been used to treat more than 17,000 people in the United States.
INCIVEK was approved by the U.S. Food and Drug Administration (FDA) in May 2011 and by Health Canada in August 2011 for people with genotype 1 chronic hepatitis C with compensated liver disease (some level of damage to the liver but the liver still functions), including cirrhosis (scarring of the liver). INCIVEK is approved for people who are new to treatment, and for people who were treated previously but who did not achieve a sustained viral response, or viral cure (relapsers, partial responders and null responders).
VX-222 is an oral medicine in development that is a non-nucleoside inhibitor of the HCV NS5B polymerase. VX-222 is currently being evaluated in combination with INCIVEK, pegylated-interferon and ribavirin in a Phase 2 study. Vertex has worldwide commercial rights for VX-222.
INCIVEK (750 mg) is given as two 375 mg tablets three times daily for 12 weeks in combination with pegylated-interferon and ribavirin. Each monthly package of INCIVEK contains four weekly boxes that include daily blister strips. After the first 12 weeks, all patients stop receiving INCIVEK and continue treatment with pegylated-interferon and ribavirin alone for an additional 12 weeks or 36 weeks of treatment. With INCIVEK combination therapy, more than 60 percent of people treated for the first time, as well as those who relapsed after previous therapy, are expected to complete all treatment in 24 weeks. All other patients receive a total of 48 weeks of treatment. A Phase 3 study evaluating twice-daily dosing of INCIVEK is ongoing.
Rash and anemia are the most serious side effects associated with INCIVEK, which led to treatment discontinuation in about 1 percent of people in clinical studies. The most common side effects reported with INCIVEK combination treatment include fatigue, itching, nausea, diarrhea, vomiting, anal or rectal problems, and taste changes.
Vertex developed telaprevir in collaboration with Tibotec BVBA and Mitsubishi Tanabe Pharma. Vertex has rights to commercialize telaprevir in North America where it is being marketed under the brand name INCIVEK (in-SEE-veck). Through its affiliate, Janssen, Tibotec has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. In September 2011, telaprevir was approved in the European Union and Switzerland. Telaprevir is known as INCIVO® in Europe. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries. In September 2011, telaprevir was approved in Japan and will be known as Telavic®.
IMPORTANT SAFETY INFORMATION
Indication
INCIVEK™ (telaprevir) is a prescription medicine used with the medicines peginterferon alfa and ribavirin to treat chronic (lasting a long time) hepatitis C genotype 1 infection in adults with stable liver problems, who have not been treated before or who have failed previous treatment. It is not known if INCIVEK is safe and effective in children under 18 years of age.
Important Safety Information
INCIVEK should always be taken in combination with peginterferon alfa and ribavirin. Ribavirin may cause birth defects or death of an unborn baby. Therefore, a patient should not take INCIVEK combination treatment if she is pregnant or may become pregnant, or if he is a man with a sexual partner who is pregnant. Patients must use two forms of effective birth control during treatment and for the 6 months after treatment with these medicines.
INCIVEK and other medicines can affect each other and can also cause side effects that can be serious or life threatening. There are certain medicines patients cannot take with INCIVEK combination treatment. Patients should tell their healthcare providers about all the medicines they take, including prescription and non-prescription medicines, vitamins and herbal supplements.
INCIVEK can cause serious side effects including rash and anemia. The most common side effects of INCIVEK include itching, nausea, diarrhea, vomiting, anal or rectal problems, taste changes and tiredness. There are other possible side effects of INCIVEK, and side effects associated with peginterferon alfa and ribavirin also apply to INCIVEK combination treatment. Patients should tell their healthcare providers about any side effect that bothers them or doesn't go away.
Please see full Prescribing Information for INCIVEK including the Medication Guide, available at www.INCIVEK.com.
INCIVEK™ is a trademark of Vertex Pharmaceuticals Incorporated.
PEGASYS® and COPEGUS® are registered trademarks of Hoffmann-La Roche.
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.1 Chronic hepatitis C can lead to serious and life-threatening liver problems, including liver damage, cirrhosis, liver failure or liver cancer.1 Though many people with hepatitis C may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.1
Unlike HIV and hepatitis B virus, chronic hepatitis C can be cured.2 However, approximately 60 percent of people do not achieve SVR,3,4,5 or viral cure,6 after treatment with 48 weeks of pegylated-interferon and ribavirin alone. 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
More than 170 million people worldwide are chronically infected with hepatitis C.6 In the United States, nearly 4 million people have chronic hepatitis C and 75 percent of them are unaware of their infection.9 Hepatitis C is four times more prevalent in the United States compared to HIV.9 The majority of people with hepatitis C in the United States were born between 1946 and 1964, accounting for two of every three people with chronic hepatitis C.10 Hepatitis C is the leading cause of liver transplantations in the United States and is reported to contribute to 4,600 to 12,000 deaths annually.11,12 By 2029, total annual medical costs in the United States for people with hepatitis C are expected to more than double, from $30 billion in 2009 to approximately $85 billion.9
Special Note Regarding Forward-Looking Statements
This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including statements regarding (i) the intent to initiate Phase 3 studies for the QUAD regimen in the first quarter of 2012; (ii) the potential to achieve high viral cure rates with just 12 weeks of therapy; (iii) Vertex’s discussions with regulatory authorities regarding future clinical trials and (iv) end-of-treatment data from the all-oral arms of the ZENITH study. While the company believes the forward-looking statements contained in this press release are accurate, there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, that the interim data presented in this press release may not be predictive of the final outcomes from this clinical trial; the outcomes from additional arms in this clinical trial and/or from any future clinical trials of telaprevir/VX-222 may not be favorable; future scientific, clinical, competitive or other market factors may adversely affect the potential for telaprevir/VX-222-based therapy and the other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through Vertex's website at www.vrtx.com. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.
About Vertex
Vertex creates new possibilities in medicine. Our team discovers, develops and commercializes innovative therapies so people with serious diseases can lead better lives.
Vertex scientists and our collaborators are working on new medicines to cure or significantly advance the treatment of hepatitis C, cystic fibrosis, rheumatoid arthritis, epilepsy and other life-threatening diseases.
Founded more than 20 years ago in Cambridge, MA, we now have ongoing worldwide research programs and sites in the U.S., U.K. and Canada. Today, Vertex has more than 1,900 employees around the world, and Science magazine named Vertex number one on its 2011 list of Top Employers in the life sciences.
INCIVEKTM is a trademark of Vertex Pharmaceuticals Incorporated.
PEGASYS® and COPEGUS® are registered trademarks of Hoffmann-La Roche.
1 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 March 21, 2011.
2 Pearlman BL and Traub N. Sustained Virologic Response to Antiviral Therapy for Chronic Hepatitis C Virus Infection: A Cure and So Much More. Clin Infect Dis. 2011 Apr;52(7):889-900.
3 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.
4 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.
5 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.
6 Ghany MG, Strader DB, Thomas DL, Seeff, LB. Diagnosis, management and treatment of hepatitis C; An update. Hepatology. 2009;49 (4):1-40.
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 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.
9 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. Available at: 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 March 21, 2011.
10 Pyenson B, Fitch K, Iwasaki K. Consequences of hepatitis C virus (HCV): Costs of a baby boomer epidemic of liver disease. Available at: http://www.natap.org/2009/HCV/051809_01.htm. Updated May 2009. Accessed March 21, 2011. This report was commissioned by Vertex Pharmaceuticals, Inc.
11 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.
12 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.
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