- all major subgroups achieved significantly higher viralcure rates with telaprevir-based therapy compared topegylated-interferon and ribavirin: 86% vs. 24% in prior relapsers,57% vs. 15% in prior partial responders and 31% vs. 5% in priornull responders -
- No clinical benefit was observed in delaying telaprevirtherapy by four weeks (lead-in) compared to starting telaprevir,pegylated-interferon and ribavirin simultaneously -
- Safety and tolerability results were consistent with priorPhase 3 studies of telaprevir -
BERLIN–(BUSINESS WIRE)–Mar 31, 2011 – Vertex PharmaceuticalsIncorporated (Nasdaq: VRTX) today announced final results from itspivotal Phase 3 REALIZE study that evaluated people with genotype 1chronic hepatitis C whose prior treatment with pegylated-interferonand ribavirin was unsuccessful either because they relapsed, had apartial response or had a null response. Data from the study showedthat people in each of these subgroups who were treated withtelaprevir-based combination therapy achieved superior rates ofsustained viral response (SVR, or viral cure) compared to thosetreated with pegylated-interferon and ribavirin alone.
REALIZE also evaluated whether viral cure rates could be furtherimproved by delaying the start of telaprevir by four weeks, duringwhich time patients received four weeks of pegylated-interferon andribavirin alone (lead-in), compared to a simultaneous start. Thedata showed no clinical benefit to a lead-in for people treatedwith telaprevir-based combination therapy. Safety and tolerabilityresults were consistent with results from the prior Phase 3 studiesof telaprevir. These data were presented today at The InternationalLiver Congress™ 2011, 46th annual meeting of theEuropean Association for the Study of the Liver (EASL) in Berlin,Germany. REALIZE was conducted by Vertex’s collaborator, TibotecBVBA.
“Patients with chronic hepatitis C who undergore-treatment with currently available medicines rarely achieve aviral cure and remain at an increased risk for advancing to moreserious liver disease,” said Stefan Zeuzem, M.D., Professorof Medicine and Chief of the Department of Medicine at the JWGoethe University Hospital, Frankfurt, Germany and principalinvestigator for REALIZE. “These data are important becausethey showed that viral cure rates were three to six times higherfor patients treated with a telaprevir-based regimen compared tore-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 partialresponders and 29 percent (21/72) of null responders achieved viralcures compared to 24 percent (16/68), 15 percent (4/27) and 5percent (2/37), respectively, who received pegylated-interferon andribavirin. The viral cure rates among those in the lead-in arm were88 percent (124/141) among prior relapsers, 54 percent (26/48)among prior partial responders and 33 percent (25/75) among priornull responders. In a combined endpoint analysis of the twotelaprevir-based treatment arms, 86 percent (245/286) of priorrelapsers, 57 percent (55/97) of prior partial responders and 31percent (46/147) of prior null responders achieved viral cures.
“The REALIZE results are encouraging, especiallyconsidering people in this study had been unsuccessfully treated inthe past and many already had scarring of the liver,” saidRobert Kauffman, M.D., Ph.D., Senior Vice President and ChiefMedical Officer for Vertex. “Rates of viral cure among thosetreated with telaprevir-based regimens were similar between thesimultaneous and delayed start arms of the study, supporting theconclusion that there was no clinical benefit to a lead-in strategywith telaprevir.”
In this study, 48 percent (316/662) of patients overall hadadvanced liver fibrosis or cirrhosis (scarring of the liver) and 89percent (586/662) of patients overall had high amounts of hepatitisC virus (high viral load; HCV RNA ‰¥ 800,000 IU/mL) uponstudy entry.
Summary of REALIZE Results
REALIZE is the only Phase 3 hepatitis C study to date of adirect-acting antiviral medicine in development that was designedto evaluate people whose prior treatment was unsuccessful,including those who had a null response. In this study, patientswere randomized 2:2:1 to two telaprevir-based treatment arms(simultaneous or lead-in) or a control arm of 48 weeks ofpegylated-interferon and ribavirin alone. Patients in thetelaprevir treatment arms received a total of 12 weeks oftelaprevir-based combination therapy. In the lead-in arm, patientsreceived four weeks of pegylated-interferon and ribavirin followedby telaprevir in combination with pegylated-interferon andribavirin for 12 weeks followed by 32 weeks of pegylated-interferonand ribavirin alone. For those in the simultaneous start arm, thetelaprevir-based combination was followed by an additional 36 weeksof pegylated-interferon and ribavirin alone. The primary endpointof the REALIZE study was SVR in each of the two telaprevirtreatment arms compared to the control arm and for the three groupsof people included in the study. The total treatment time for allpatients in REALIZE was 48 weeks.
REALIZESVRResults % (n) PriorRelapsers (n=354)* PriorPartial Responders (n=124)* PriorNull Responders (n=184)*TVR-based Simultaneous Start Arm+ 83% 59% 29%TVR-based Lead-In Arm++ 88% 54% 33%ControlArm+++ 24% 15% 5%he 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 ofTelaprevir
The safety and tolerability results of the telaprevir-basedcombination 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 diarrheawith the majority being mild to moderate. Rash and anemia occurredmore frequently in the telaprevir-based treatment arms compared tothe control group.
Rash was primarily characterized as eczema-like, manageable andresolved upon stopping telaprevir. More than 90 percent of rash wasmild to moderate and primarily managed with the use of topicalcorticosteroids and/or antihistamines. Anemia was primarily managedby reducing the dose of ribavirin.
To optimize each patient’s opportunity to achieve viral cure inthe Phase 3 studies, sequential discontinuation of the medicineswas recommended as a strategy to manage certain adverse events.this strategy allowed patients to continue on pegylated-interferonand ribavirin after stopping telaprevir. Discontinuation of allmedicines due to either rash or anemia during thetelaprevir/placebo treatment phase was 1 percent to 3 percent inthe telaprevir treatment arms.
About the Study
REALIZE was a pivotal Phase 3, randomized, double-blind,placebo-controlled, global study. The majority of clinical trialsites were in Europe. The study was designed to evaluate theefficacy, safety and tolerability of telaprevir-based combinationregimens in people infected with genotype 1 chronic hepatitis C whodid not achieve a viral cure after at least one course of priortreatment with interferon-based therapy.
Status of Telaprevir Regulatory Applications
The regulatory applications for the approval of telaprevir havebeen granted Priority Review by the U.S. Food and DrugAdministration (FDA) and Health Canada and accelerated assessmentby the European Medicines Agency for the treatment of people withgenotype 1 chronic hepatitis C. The FDA has scheduled its AntiviralDrugs Advisory Committee to discuss the New Drug Application fortelaprevir on April 28, 2011. A target response date of May 23,2011 is set under the Prescription Drug User Fee Act (PDUFA). Theapplications include data from three registration studies, ADVANCE,ILLUMINATE and REALIZE, which evaluated telaprevir in combinationwith pegylated-interferon and ribavirin in people with hepatitis Cwho were new to treatment as well as those who did not achieve aviral cure after treatment with currently available medicines. Forcomplete information on the telaprevir clinical trials or a factsheet on the trial designs visit: vrtx.com/press.cfm.
About the Telaprevir Development Program
Telaprevir is an investigational, oral inhibitor that actsdirectly on the HCV protease, an enzyme essential for viralreplication. to date, more than 2,500 people with hepatitis C havereceived telaprevir-based therapy as part of Phase 2 studies andthe Phase 3 ADVANCE, ILLUMINATE and REALIZE studies. together,these studies enrolled people with genotype 1 chronic hepatitis Cwho had not been treated for their disease previously as well aspeople who had been treated before but did not achieve a viralcure.
Vertex is developing telaprevir in collaboration with TibotecBVBA and Mitsubishi Tanabe Pharma. Vertex has rights tocommercialize telaprevir in North America. Through its affiliate,Janssen, Tibotec has rights to commercialize telaprevir in Europe,South America, Australia, the Middle East and certain othercountries. Mitsubishi Tanabe Pharma has rights to commercializetelaprevir in Japan and certain Far East countries.
About Hepatitis C
Hepatitis C is a serious liver disease caused by the hepatitis Cvirus, which is spread through direct contact with the blood ofinfected people and ultimately affects the liver.1Chronic hepatitis C can lead to serious and life-threatening liverproblems, including liver damage, cirrhosis, liver failure or livercancer.1 Though many people with hepatitis C may notexperience symptoms, others may have symptoms such as fatigue,fever, jaundice and abdominal pain.1 Approximately 60percent of people who undergo treatment with an initial 48-weekregimen with pegylated-interferon and ribavirin, the currentlyapproved medicines for genotype 1 hepatitis C, do not achieveSVR,2,3,4 or viral cure.5 if treatment is notsuccessful and a person does not achieve a viral cure, they remainat an increased risk for progressive liverdisease.6,7
More than 170 million people worldwide are chronically infectedwith hepatitis C.5 In the United States, nearly 4million people have chronic hepatitis C and 75 percent of them areunaware of their infection.8 The majority of people withhepatitis C in the United States were born between 1946 and 1964,accounting for two of every three people with chronic hepatitisC.9 Hepatitis C is the leading cause of livertransplantations in the United States and is reported to contributeto 4,600 to 12,000 deaths annually.10,11 By 2029, totalannual medical costs in the United States for people with hepatitisC are expected to more than double, from $30 billion in 2009 toapproximately $85 billion.9
PEGASYS® and COPEGUS® areregistered trademarks of Hoffmann-La Roche.
Special Note Regarding Forward-Looking Statements
This press release contains forward-looking statements asdefined in the Private Securities Litigation Reform Act of 1995,including statements regarding (i) the date of the scheduledmeeting of the FDA’s Antiviral Advisory Committee and (ii) theFDA’s target review date for the telaprevir NDA. While the companybelieves the forward-looking statements contained in this pressrelease are accurate, there are a number of factors that couldcause actual events or results to differ materially from thoseindicated by such forward-looking statements. Those risks anduncertainties include, among other things, that Vertex couldexperience unforeseen delays in obtaining approval to markettelaprevir; that there may be varying interpretations of the datafrom the telaprevir clinical trials; that future outcomes fromclinical trials of telaprevir may not be favorable; that futurescientific, clinical, competitive or other market factors mayadversely affect the potential for telaprevir-based therapy and theother risks listed under Risk Factors in Vertex’s annual report andquarterly reports filed with the Securities and Exchange Commissionand available through Vertex’s website at vrtx.com. Vertex disclaims any obligation to update theinformation contained in this press release as new informationbecomes available.
About Vertex
Vertex creates new possibilities in medicine. our team aims todiscover, develop and commercialize innovative therapies so peoplewith serious diseases can lead better lives.
Vertex scientists and our collaborators are working on newmedicines to cure or significantly advance the treatment ofhepatitis C, cystic fibrosis, epilepsy and other life-threateningdiseases.
Founded more than 20 years ago in Cambridge, MA, we now haveongoing worldwide research programs and sites in the U.S., U.K. andCanada.
For more information and to view Vertex’s press releases, pleasevisit vrtx.com.
1 Centers for Disease Control and Prevention.Hepatitis C Fact Sheet: CDC Viral Hepatitis. available at: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 interferonalfa-2b plus ribavirin for initial treatment of chronic hepatitisC: 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 virusinfection. 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 ribavirinfor 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 inthe Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis(HALT-C) trial. Hepatology. 2008;50(Suppl 4):357A (Abstract115).
7 Veldt BJ, Heathcote J, Wedmeyer H. Sustainedvirologic response and clinical outcomes in patients with chronichepatitis 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 andcontrol of hepatitis B and C. Colvin HM and Mitchell AE, ed.available at: 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 ofhepatitis C virus (HCV): Costs of a baby boomer epidemic of liverdisease. available at: natap.org/2009/HCV/051809_01.htm. Updated May 2009.Accessed March 21, 2011. This report was commissioned by VertexPharmaceuticals, inc.
10 Volk MI, Tocco R, Saini S, Lok, ASF. Public healthimpact 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 inthe United States: A multiple cohort model of HCV prevalence anddisease progression. Gastroenterology. 2010;138:513-521.
Contact: Vertex Pharmaceuticals IncorporatedMedia:Dawn KalmarAmy PasquaZachry Barber617-444-6992 or Investors:Michael Partridge, 617-444-6108orLora Pike, 617-444-6755orMatthew Osborne, 617-444-6057