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  EASL 46th Annual Meeting
March 30th - April 3rd 2011
Berlin, Germany
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Results From Phase 3 REALIZE Study Showed Telaprevir-Based Therapy Significantly Improved SVR (Viral Cure) Rates in People Whose Prior Treatment For Hepatitis C Was Unsuccessful
  - All major subgroups achieved significantly higher viral cure rates with telaprevir-based therapy compared to pegylated-interferon and ribavirin: 86% vs. 24% in prior relapsers, 57% vs. 15% in prior partial responders and 31% vs. 5% in prior null responders -
- No clinical benefit was observed in delaying telaprevir therapy by four weeks (lead-in) compared to starting telaprevir, pegylated-interferon and ribavirin simultaneously -
- Safety and tolerability results were consistent with prior Phase 3 studies of telaprevir -
vertex press release March 31 2011
BERLIN- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced final results from its pivotal Phase 3 REALIZE study that evaluated people with genotype 1 chronic hepatitis C whose prior treatment with pegylated-interferon and ribavirin was unsuccessful either because they relapsed, had a partial response or had a null response. Data from the study showed that people in each of these subgroups who were treated with telaprevir-based combination therapy achieved superior rates of sustained viral response (SVR, or viral cure) compared to those treated with pegylated-interferon and ribavirin alone.
REALIZE also evaluated whether viral cure rates could be further improved by delaying the start of telaprevir by four weeks, during which time patients received four weeks of pegylated-interferon and ribavirin alone (lead-in), compared to a simultaneous start. The data showed no clinical benefit to a lead-in for people treated with telaprevir-based combination therapy. Safety and tolerability results were consistent with results from the prior Phase 3 studies of telaprevir. These data were presented today at The International Liver Congress 2011, 46th annual meeting of the European Association for the Study of the Liver (EASL) in Berlin, Germany. REALIZE was conducted by Vertex's collaborator, Tibotec BVBA.
"Patients with chronic hepatitis C who undergo re-treatment with currently available medicines rarely achieve a viral cure and remain at an increased risk for advancing to more serious liver disease," said Stefan Zeuzem, M.D., Professor of Medicine and Chief of the Department of Medicine at the JW Goethe University Hospital, Frankfurt, Germany and principal investigator for REALIZE. "These data are important because they showed that viral cure rates were three to six times higher for patients treated with a telaprevir-based regimen compared to re-treatment with currently available medicines."
Among those in the simultaneous start arm of REALIZE, 83 percent (121/145) of prior relapsers, 59 percent (29/49) of prior partial responders and 29 percent (21/72) of null responders achieved viral cures compared to 24 percent (16/68), 15 percent (4/27) and 5 percent (2/37), respectively, who received pegylated-interferon and ribavirin. The viral cure rates among those in the lead-in arm were 88 percent (124/141) among prior relapsers, 54 percent (26/48) among prior partial responders and 33 percent (25/75) among prior null responders. In a combined endpoint analysis of the two telaprevir-based treatment arms, 86 percent (245/286) of prior relapsers, 57 percent (55/97) of prior partial responders and 31 percent (46/147) of prior null responders achieved viral cures.
"The REALIZE results are encouraging, especially considering people in this study had been unsuccessfully treated in the past and many already had scarring of the liver," said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer for Vertex. "Rates of viral cure among those treated with telaprevir-based regimens were similar between the simultaneous and delayed start arms of the study, supporting the conclusion that there was no clinical benefit to a lead-in strategy with telaprevir."
In this study, 48 percent (316/662) of patients overall had advanced liver fibrosis or cirrhosis (scarring of the liver) and 89 percent (586/662) of patients overall had high amounts of hepatitis C virus (high viral load; HCV RNA ≥ 800,000 IU/mL) upon study entry.
Summary of REALIZE Results
REALIZE is the only Phase 3 hepatitis C study to date of a direct-acting antiviral medicine in development that was designed to evaluate people whose prior treatment was unsuccessful, including those who had a null response. In this study, patients were randomized 2:2:1 to two telaprevir-based treatment arms (simultaneous or lead-in) or a control arm of 48 weeks of pegylated-interferon and ribavirin alone. Patients in the telaprevir treatment arms received a total of 12 weeks of telaprevir-based combination therapy. In the lead-in arm, patients received four weeks of pegylated-interferon and ribavirin followed by telaprevir in combination with pegylated-interferon and ribavirin for 12 weeks followed by 32 weeks of pegylated-interferon and ribavirin alone. For those in the simultaneous start arm, the telaprevir-based combination was followed by an additional 36 weeks of pegylated-interferon and ribavirin alone. The primary endpoint of the REALIZE study was SVR in each of the two telaprevir treatment arms compared to the control arm and for the three groups of people included in the study. The total treatment time for all patients in REALIZE was 48 weeks.


*The SVR rates observed were statistically significant when compared with the control arm (p <0.001).
+Simultaneous start: 12 weeks of telaprevir (750 mg, q8h), Pegasys® (PEG, pegylated-interferon alfa-2a) & Copegus® (RBV, ribavirin), followed by 36 weeks of PEG & RBV alone
++Lead-in: 4 weeks of PEG & RBV alone followed by 12 weeks of telaprevir (750 mg, q8h), PEG & RBV, followed by 32 weeks of PEG & RBV alone. There was no clinical benefit with the use of a four-week lead in with no significant improvement in SVR rates and no significant reduction in virologic failure and relapse rates in the lead-in start arm compared to the simultaneous start arm.
+++Control: 12 weeks of placebo, PEG & RBV, followed by 36 weeks of Peg & RBV alone.
Prior Relapser: Defined as a person whose hepatitis C virus was undetectable at the completion of at least 42 weeks of a prior course of therapy but whose virus became detectable during the follow-up period.
Prior Partial Responder: Defined as a person who achieved at least a 2 log in10 reduction in HCV RNA at week 12, but whose hepatitis C virus never became undetectable by week 24 of a prior course of therapy.
Prior Null Responder: Defined as a person who achieved a less than 2 log10 reduction in HCV RNA at week 12 of a prior course of therapy.
Safety and Tolerability Information for the Phase 3 Studies of Telaprevir
The safety and tolerability results of the telaprevir-based combination regimens were consistent across the Phase 3 studies. The most common adverse events were fatigue, pruritus, nausea, headache, rash, anemia, flu-like symptoms, insomnia and diarrhea with the majority being mild to moderate. Rash and anemia occurred more frequently in the telaprevir-based treatment arms compared to the control group.
Rash was primarily characterized as eczema-like, manageable and resolved upon stopping telaprevir. More than 90 percent of rash was mild to moderate and primarily managed with the use of topical corticosteroids and/or antihistamines. Anemia was primarily managed by reducing the dose of ribavirin.
To optimize each patient's opportunity to achieve viral cure in the Phase 3 studies, sequential discontinuation of the medicines was recommended as a strategy to manage certain adverse events. This strategy allowed patients to continue on pegylated-interferon and ribavirin after stopping telaprevir. Discontinuation of all medicines due to either rash or anemia during the telaprevir/placebo treatment phase was 1 percent to 3 percent in the telaprevir treatment arms.
About the Study
REALIZE was a pivotal Phase 3, randomized, double-blind, placebo-controlled, global study. The majority of clinical trial sites were in Europe. The study was designed to evaluate the efficacy, safety and tolerability of telaprevir-based combination regimens in people infected with genotype 1 chronic hepatitis C who did not achieve a viral cure after at least one course of prior treatment with interferon-based therapy.
Status of Telaprevir Regulatory Applications
The regulatory applications for the approval of telaprevir have been granted Priority Review by the U.S. Food and Drug Administration (FDA) and Health Canada and accelerated assessment by the European Medicines Agency for the treatment of people with genotype 1 chronic hepatitis C. The FDA has scheduled its Antiviral Drugs Advisory Committee to discuss the New Drug Application for telaprevir on April 28, 2011. A target response date of May 23, 2011 is set under the Prescription Drug User Fee Act (PDUFA). The applications include data from three registration studies, ADVANCE, ILLUMINATE and REALIZE, which evaluated telaprevir in combination with pegylated-interferon and ribavirin in people with hepatitis C who were new to treatment as well as those who did not achieve a viral cure after treatment with currently available medicines. For complete information on the telaprevir clinical trials or a fact sheet on the trial designs visit: www.vrtx.com/press.cfm.
About the Telaprevir Development Program
Telaprevir is an investigational, oral inhibitor that acts directly on the HCV protease, an enzyme essential for viral replication. To date, more than 2,500 people with hepatitis C have received telaprevir-based therapy as part of Phase 2 studies and the Phase 3 ADVANCE, ILLUMINATE and REALIZE studies. Together, these studies enrolled people with genotype 1 chronic hepatitis C who had not been treated for their disease previously as well as people who had been treated before but did not achieve a viral cure.
Vertex is developing telaprevir 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 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 Approximately 60 percent of people who undergo treatment with an initial 48-week regimen with pegylated-interferon and ribavirin, the currently approved medicines for genotype 1 hepatitis C, do not achieve SVR,2,3,4 or viral cure.5 If treatment is not successful and a person does not achieve a viral cure, they remain at an increased risk for progressive liver disease.6,7
More than 170 million people worldwide are chronically infected with hepatitis C.5 In the United States, nearly 4 million people have chronic hepatitis C and 75 percent of them are unaware of their infection.8 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.9 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.10,11 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
PEGASYS® and COPEGUS® are registered trademarks of Hoffmann-La Roche.
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 date of the scheduled meeting of the FDA's Antiviral Advisory Committee and (ii) the FDA's target review date for the telaprevir NDA. 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 Vertex could experience unforeseen delays in obtaining approval to market telaprevir; that there may be varying interpretations of the data from the telaprevir clinical trials; that future outcomes from clinical trials of telaprevir may not be favorable; that future scientific, clinical, competitive or other market factors may adversely affect the potential for telaprevir-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 aims to discover, develop and commercialize 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, 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.
For more information and to view Vertex's press releases, please visit www.vrtx.com.
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 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.
3 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.
4 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.
5 Ghany MG, Strader DB, Thomas DL, Seeff, LB. Diagnosis, management and treatment of hepatitis C; An update. Hepatology. 2009;49 (4):1-40.
6 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).
7 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.
8 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.
9 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.
10 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.
11 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.
Vertex Pharmaceuticals Incorporated