EASL VX-222 Plus Telaprevir,Peg/Riba Interim Phase 2 Data; Undetectable Viral Load At 12wks

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EASL "VX-222 Plus Telaprevir,Peg/Riba" Interim Phase 2 Data; Undetectable Viral Load At 12wks

Vertex said Thursday the combination of telaprevir and VX-222 with pegylated-interferon and ribavirin treatment in HCV genotype 1, naive - "never treated before" patients met its safety goal . The four drug combination showed that 90% of participants were undetectable by week 12. Previously ,Vertex halted other arms of telaprevir and VX-222 ; In October of 2010 the VX-222/telaprevir combo being tested in low doses was stopped because of viral breakthrough. In December 2010 in a higher dose of the VX-222/telaprevir combo was halted in part of the Vertex study. Also See HIV and Hepatitis 4-Drug Combo with Telaprevir and VX-222 ClearsHCV at 12 WeeksSUMMARY: 90% of previously untreated genotype 1 chronic hepatitis C patients treated with telaprevir plus VX-222 plus pegylated interferon and ribavirin achieved undetectable viral load at week 12, researchers reported at EASL 2011. .Interim Phase 2 Data Showed Rapid Viral Response to VX-222 in Combination with Telaprevir, Pegylated-Interferon and Ribavirin Among People With Hepatitis CBERLIN--(BUSINESS WIRE)--Mar 31, 2011 - Vertex PharmaceuticalsIncorporated (Nasdaq: VRTX) today announced interim results from anongoing Phase 2 study (ZENITH) designed to assess the safety andtolerability of 12-week response-guided treatment regimens with itspolymerase inhibitor, VX-222, and its protease

inhibitor,telaprevir, in combination with pegylated-interferon and ribavirinin people with genotype 1 chronic hepatitis C who were new totreatment. The study enrolled 106 people into one of four treatmentgroups. Among those who received VX-222 (400 mg) in combinationwith telaprevir, pegylated-interferon and ribavirin, interim datashowed that 90 percent (27/30) of them had undetectable hepatitis Cvirus at week 12. Half (15/30) of those in the VX-222 (400 mg)treatment group were eligible to stop all treatment at week 12.People in this same treatment group who were not eligible to stopall treatment at 12 weeks were assigned to receive 24 total weeksof treatment: 12 weeks of the four-drug regimen followed by 12weeks of pegylated-interferon and ribavirin alone. Preliminarysafety results showed that the most frequently reported adverseevents were mild gastrointestinal symptoms and mild fatigue. At

thetime of this analysis, there were no discontinuations due togastrointestinal symptoms. Data from this study are being presentedtoday at The International Liver Congressâ„¢ 2011, the46th annual meeting of the European Association for theStudy of the Liver (EASL) in Berlin, Germany.“Telaprevir triple therapy demonstrated significantimprovements in viral cure rates and an ability to halve treatmenttime to 24 weeks for many people in late-stage studies,†said Kauffman, M.D., Ph.D., Senior Vice President and ChiefMedical Officer for Vertex. “Reducing treatment time in halfagain to 12 weeks would be another important advance and the earlydata from this study provide new information about the potential todo this with a four-drug VX-222 regimen.â€Using an intent-to-treat analysis, 57 percent (17/30) of peopletreated with VX-222 (400 mg) in combination with

telaprevir,pegylated-interferon and ribavirin had undetectable hepatitis Cvirus by week two. Among people who were treated with VX-222 (100mg) in combination with telaprevir, pegylated-interferon andribavirin, 38 percent (11/29) had undetectable hepatitis C virus byweek two. To determine if patients were eligible to stop alltreatment at 12 weeks in ZENITH, they had to have undetectablehepatitis C virus at weeks two and eight. Using the eligibilitycriteria for a 12-week total treatment duration, half (15/30) ofthe patients in the high-dose VX-222 combination group and 38percent (11/29) in the low-dose combination group were eligible tostop all treatment at 12 weeks. Ninety percent (27/30) of patientsin the high-dose VX-222 group had undetectable hepatitis C virus byweek 12 as did 83 percent (24/29) in the low-dose VX-222 group. Noviral breakthrough was observed through week 12 among

patientsreceiving the four-drug combinations.“The early data from this study are encouraging becausethey showed patients had a very rapid decline in hepatitis C virusas early as the second week of treatment,†said DiBisceglie, M.D., Chief of Hepatology at Saint Louis UniversitySchool of Medicine. “Hepatitis C virus was undetectable atweek 12 of treatment in 90 percent of patients who received thehigher dose of VX-222, and half of those in this treatment groupwere eligible to stop all treatment at that time.â€ZENITH is an ongoing Phase 2 study that enrolled 106 people andbegan with four treatment arms evaluating two-drug and four-drugcombination regimens. The primary endpoint is safety andtolerability and the secondary endpoint is on-treatment antiviralactivity and the proportion of people in each treatment arm whoachieve a sustained viral response (SVR, defined as

undetectablehepatitis C virus 24 weeks after the end of treatment). The studyis designed to evaluate various combinations of VX-222, telaprevir,pegylated-interferon and ribavirin for the treatment of genotype 1chronic hepatitis C. In this study, VX-222, telaprevir andribavirin are given twice daily. Arms A (n=18) and B (n=29) weredesigned to evaluate the all-oral, two-drug combination regimens ofVX-222 (400 mg or 100 mg) and telaprevir (1,125 mg). Both of thesestudy arms were discontinued due to a pre-defined stopping rulerelated to viral breakthrough. Arms C (n=29) and D (n=30) areongoing and designed to evaluate the four-drug combination regimensof VX-222 (400 mg and 100 mg), telaprevir (1,125 mg),pegylated-interferon and ribavirin. An additional treatment arm hasbeen added to the study to evaluate an all-oral, three-drug regimenof VX-222, telaprevir and ribavirin in people with genotype

1bchronic hepatitis C. This study arm is now open for enrollment. Asixth and final arm may be added to the trial per protocol based ondata from the study.

ZENITH: Interim Intent to Treat (ITT) Analysis of Arms C and D

VX-222 (100 mg) /TVR-

basedarm(+)

VX-222 (400 mg) /TVR-based arm(++)

Week 2 HCV RNAundetectable

38%

57%

(11/29)

(17/30)

Week 2 and 8 HCVRNA

38%

50%

undetectable*

(11/29)

(15/30)

Week 4 HCV RNAundetectable

86%

87%

(RVR)

(25/29)

(26/30)

Weeks12 HCV RNA undetectable

83%

90%

(eRVR)

(24/29)

(27/30)

HCV RNAwas evaluated using the TaqMan assay version 2.0.*As part of a response-guided regimen, people who haveundetectable hepatitis C virus at weeks 2 and 8 are eligible tostop all treatment at week 12.+VX-222 (100 mg, BID), telaprevir (1,125 mg, BID),Pegasys® (pegylated-interferon alfa-2a) andCopegus® (ribavirin).++VX-222 (400 mg, BID), telaprevir (1,125 mg, BID),Pegasys® (pegylated-interferon alfa-2a) andCopegus® (ribavirin).

Preliminary Safety and TolerabilityThe 12-week safety and tolerability results are preliminary andinclude data on all patients enrolled in the study: those enrolledin the two-drug (n=47) and four-drug (n=59) treatment arms. Themost frequent adverse events observed in this study were mildgastrointestinal symptoms (including diarrhea, nausea and vomiting)and mild fatigue. No patients discontinued due to gastrointestinalsymptoms.Preliminary safety data indicate that there were sixdiscontinuations due to adverse events among the four treatmentarms through week 12. There were two serious adverse eventsconsidered by the investigator to be potentially related to studymedication: acute renal failure (Arm , which resolved after studymedications were discontinued and anemia (Arm C). There was oneadditional severe adverse event reported of pneumonia, septic

shockand renal failure; this severe adverse event was considered by theinvestigator to be unrelated to study medication. The threeadditional discontinuations included rash (n=2) and a motor vehicleaccident with facial fractures (n=1).About Telaprevir and VX-222Vertex has two oral medicines in development for the treatmentof genotype 1 chronic hepatitis C: telaprevir and VX-222.Telaprevir is an investigational, oral inhibitor that acts directlyon the HCV protease, an enzyme essential for viral replication. Todate, more than 2,500 people with genotype 1 chronic hepatitis Chave received telaprevir in Phase 2 and Phase 3 studies. Vertex hasbeen granted Priority Review for its applications for the approvalof telaprevir by the U.S. Food and Drug Administration (FDA) andHealth Canada. The FDA has scheduled its Antiviral Drugs AdvisoryCommittee to discuss the New Drug Application for

telaprevir onApril 28, 2011. A target response date of May 23, 2011 is set underthe Prescription Drug User Fee Act (PDUFA).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.VX-222 is an investigational, oral, non-nucleoside inhibitor ofHCV NS5B polymerase. VX-222 is currently being evaluated incombination with telaprevir, pegylated-interferon and ribavirin ina Phase 2 study. Vertex has worldwide commercial rights forVX-222.About Hepatitis CHepatitis 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 of an initial 48-weekregimen of 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.6,7More 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.9PEGASYS® and COPEGUS® areregistered trademarks of Hoffmann-La Roche.Special Note Regarding Forward-Looking StatementsThis press release contains forward-looking statements asdefined in the Private Securities

Litigation Reform Act of 1995,including statements regarding (i) the potential importance ofreducing treatment time to 12 weeks and early data from this studyproviding new information about the potential to do this with afour-drug VX-222 regimen; (ii) the early data being encouragingbecause the data showed patients had a very rapid decline inhepatitis C virus as early as the second week of treatment; (iii)the possibility that a sixth treatment arm may be added to thetrial; (iv) the date of the scheduled meeting of the FDA'sAntiviral Advisory Committee and (v) the FDA's target response datefor the telaprevir NDA. While the company believes theforward-looking statements contained in this press release areaccurate, there are a number of factors that could cause actualevents or results to differ materially from those indicated by suchforward-looking statements. Those risks and uncertainties

include,among other things, that Vertex could experience unforeseen delaysin obtaining approval to market telaprevir; that the interimon-treatment data presented in this press release may not bepredictive of the final outcomes from this clinical trial, outcomesfrom any future clinical trials of telaprevir/VX-222 may not befavorable; that future scientific, clinical, competitive or othermarket factors may adversely affect the potential fortelaprevir/VX-222-based therapy and the other risks listed underRisk Factors in Vertex's annual report and quarterly reports filedwith the Securities and Exchange Commission and available throughVertex's website at www.vrtx.com. Vertex disclaims any obligation to update theinformation contained in this press release as new informationbecomes available.About

VertexVertex 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 www.vrtx.com.(VRTX - GEN)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, DL, Seeff, LB. Diagnosis, management and treatment of hepatitis C; An update.

Hepatology. 2009;49 (4):1-40.6 TR, Ghany MG, Kim HY, Snow KK, 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. ls 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 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 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.Contact: Vertex Pharmaceuticals IncorporatedMedia:Dawn Kalmar, 617-444-6992Amy Pasqua, 617-444-6992Zachry Barber, 617-444-6992mediainfo@...orInvestors: Partridge, 617-444-6108Lora Pike, 617-444-6755 Osborne, 617-444-6057

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