Better Then SOC; Improvements in Viral Cure Rates W-Telaprevir-Based TX Regardless of IL28B Genotype Status

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Better Then SOC; Improvements in Viral Cure Rates W-Telaprevir-Based TX Regardless of IL28B Genotype Status

Data From Phase 3 Studies Showed Substantial Improvements in SVR(Viral Cure) Rates With Telaprevir-Based Therapy Compared to Currently Available Medicines in People With Hepatitis C, Regardlessof Their IL28B Genotype Status

90% of people with the ËœCC' variation of IL28B whowere new to treatment and received a telaprevir-based regimenachieved a viral cure, 78% of them were eligible to stop alltreatment at 24 weeks -

- Nearly three-fold improvement in viral cure rates wasobserved among people with the ËœCT' and ËœTT' variationscompared to the control group, regardless of prior treatmentexperience -BERLIN--(BUSINESS WIRE)--Mar 31, 2011 -

Vertex Pharmaceuticals

Incorporated (Nasdaq: VRTX) today announced new data fromretrospective analyses that evaluated the relationship betweenvariations at the IL28B gene and a patient's response to treatmentwith telaprevir in combination with pegylated-interferon andribavirin from two of its pivotal Phase 3 studies (ADVANCE andREALIZE) for a group of people who were tested for IL28B genotype.These analyses showed that people in these studies had substantialimprovements in sustained viral response (SVR, or viral cure) ratesacross all IL28B genotypes (CC, CT or TT) for those treated withtelaprevir-based combination therapy compared to those treated withpegylated-interferon and ribavirin alone. Telaprevir is a medicinein development for the treatment of genotype 1 chronic hepatitis C.Safety and tolerability results were consistent across the Phase 3studies of telaprevir. Data from these IL28B analyses

werepresented today at The International Liver Congressâ„¢ 2011,the 46th annual meeting of the European Association forthe Study of the Liver (EASL) in Berlin, Germany.

A specific genetic region near the IL28B gene is referred to asan IL28B genotype. The three variations of IL28B genotypes havebeen associated with a person's response to hepatitis C treatmentwith pegylated-interferon and ribavirin. The CC variation isassociated with better responses to these medicines.

“Doctors sometimes use IL28B genotype status to decidewhich patients should be treated with currently available medicinesbecause people with the CT and TT variations of IL28B tend to havesubstantially lower viral cure rates compared to those with the CCvariation,†said Ira son, M.D., Chief of the Division ofGastroenterology and Hepatology at New York-PresbyterianHospital/Weill Cornell Medical Center, and the AstorDistinguished Professor of Medicine at Weill Cornell MedicalCollege and principal investigator for the ADVANCE study. “Inthis study, telaprevir was associated with a substantialimprovement over currently available medicines, regardless of IL28Bstatus, and the greatest improvement was observed in patients withthe CT and TT variations.â€

In ADVANCE, patients were randomized 1:1:1 to receive telaprevir(eight weeks or 12 weeks) in combination with pegylated-interferonand ribavirin, followed by pegylated-interferon and ribavirin alonefor a total of either 24 weeks or 48 weeks of treatment.Eligibility for the shorter treatment duration was based on havingundetectable hepatitis C virus at weeks four and 12. Among patientsin this study tested for their IL28B genotype, 90 percent (45/50)of CC patients who received a 12-week telaprevir-based combinationregimen, achieved a viral cure and 78 percent (39/50) of them wereeligible to stop all treatment at 24 weeks. These results werecompared to 64 percent (35/55) of patients who achieved a viralcure with pegylated-interferon and ribavirin alone for 48weeks.

“The 90 percent viral cure rate among people with the CCvariation of IL28B in this study is significant, but the fact thatnearly 80 percent of them were eligible for the shorter course oftreatment is an equally important finding,†said Kauffman, M.D., Ph.D., Senior Vice President and Chief MedicalOfficer for Vertex. “Vertex plans to conduct a studyevaluating a short-duration, 12-week telaprevir-based regimen inpeople who have not been treated for hepatitis C who have the CCvariation of IL28B.â€

Data from the ADVANCE study showed that patients with the CCvariation of IL28B who were new to treatment and received atelaprevir-based combination regimen had the highest viral curerates compared to those with the CT and TT variations. Data fromboth ADVANCE and REALIZE showed a nearly three-fold improvement inviral cure rates among patients with the CT and TT variations ofIL28B who received telaprevir-based combination therapy compared tothose who received pegylated-interferon and ribavirin. Thesedifferences were observed among patients who were new to treatmentas well as those whose prior treatment for hepatitis C wasunsuccessful.

Retrospective Analysis from ADVANCE

The Phase 3 ADVANCE study evaluated people who were new totreatment for hepatitis C. The retrospective analysis of IL28Bstatus presented today includes people tested for IL28B genotype(454/1088; 42 percent). Of the patients in ADVANCE who were testedfor their IL28B genotype, the distribution of the variations wasconsistent with previously published studies in people new totreatment.1 Data from the subanalysis of IL28B status inthe control and telaprevir treatment arms (12 weeks) of the studyare shown in the table.

ADVANCE

CC (n=150)

CT (n=224)

TT (n=80)

Overall Study

TVR+

Control++

TVR+

Control++

TVR+

Control++

TVR+

Control++

RVR*

84%(42/50)

16%(9/55)

60%(41/68)

2%(2/80)

59%(13/22)

0%(0/26)

68%(246/363)

9%(34/361)

eRVR**

78%(39/50)

16%(9/55)

57%(39/68)

2%(2/80)

45%(10/22)

0%(0/26)

58%(212/363)

8%(29/361)

SVR***

90%(45/50)

64%(35/55)

71%(48/68)

25%(20/80)

73%(16/22)

23%(6/26)

75%(271/363)

44%(158/361)

Due to the de-identification procedure, only samples from Caucasian patients were included in this analysis. *RVR: rapid viral response; undetectable (less then 25 IU/mL undetectable by Roche COBAS Taqman HCV test) at week 4.**eRVR: extended rapid viral response; undetectable (less then 25 IU/mL undetectable by Roche COBAS Taqman HCV test) at weeks 4 and 12.***SVR: defined as the proportion of people who had undetectable hepatitis C virus 24 weeks after the end of all treatment; less then 25 IU/mL, undetectable by Roche COBAS Taqman HCV test.TVR+: 12 weeks of telaprevir (TVR, 750 mg, q8h), Pegasys® (PEG, pegylated-interferon alfa-2a) and Copegus® (RBV, ribavirin) followed by 12 weeks or 36 weeks of only PEG & RBV, based on response to treatment at week 4 and week 12.Control++: 12 weeks of placebo, PEG & RBV, followed by 36 weeks

of PEG & RBV alone.

Retrospective Analysis from REALIZE

The Phase 3 REALIZE study evaluated people whose prior treatmentwith pegylated-interferon and ribavirin was unsuccessful (priorrelapsers, prior partial responders and prior null responders). Ofthe patients in REALIZE who were tested for their IL28B genotype(527/662; 80 percent), the distribution of patients with the CTvariation was over-represented and the distribution of those withthe CC variation was under-represented. This is consistent withexpectations for a population that has not responded to a priorcourse of treatment.

REALIZE

SVR

CC

CT

TT

TVR+

Control++

TVR+

Control++

TVR+

Control++

PriorRelapsers

88%(51/58)

33%(4/12)

85%(100/117)

20%(6/30)

85%(29/34)

30%(3/10)

PriorPartial Responders

63%(5/8)

20%(1/5)

58%(33/57)

20%(2/10)

71%(10/14)

0%(0/5)

PriorNull Responders

40%(4/10)

n/a(0/0)

29%(27/92)

6%(1/18)

31%(10/32)

7%(1/15)

Overall

79%(60/76)

29%(5/17)

60%(160/266)

16%(9/58)

61%(49/80)

13%(4/30)

TVR+:Since there was no difference between the two telaprevir groupsstudied, SVR rates reflect the combined telaprevir-based treatmentgroups. (a) 12 weeks of telaprevir (750 mg, q8h),PEG, pegylated-interferon alfa-2a) and Copegus (RBV, ribavirin), followed by 36 weeks of PEG & RBV alone and ( 4 weeks of PEG and RBV alone followed by 12 weeks of telaprevir (750 mg, q8h), PEG and RBV, followed by 32 weeks of PEG and RBV alone. Control++: 12 weeks of placebo, PEG and RBV, followed by 36weeks of PEG and RBV alone.Relapser: Defined as a person whosehepatitis C virus was undetectable at the completion of at least 42weeks of a prior course of therapy but whose virus becamedetectable during the follow-up period.Partial Responder: Defined as aperson who achieved at least a 2

log10 reduction in HCVRNA at week 12, but whose hepatitis C virus never becameundetectable by week 24 of a prior course of therapy.Null Responder: Defined as a personwho achieved a less than 2 log10 reduction in HCV RNA atweek 12 of a prior course of therapy.

Safety and Tolerability Information from 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 groups.

Rash was primarily characterized as eczema-like, manageable andresolved upon stopping telaprevir. More than 90 percent of rash wasmild to moderate and was 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 IL28B

IL28B is a gene related to the interferon system. A geneticregion near the IL28B gene is referred to as an IL28B genotype.There are three variations of IL28B genotypes: CC, CT or TT. Thesevariations have been associated with a person's response totreatment for hepatitis C with pegylated-interferon and ribavirin.Studies have shown that people with the CC variation respond betterto treatment with pegylated-interferon and ribavirin than thosewith the CT or TT variations. The CC variation is more frequent inCaucasians compared to African Americans (39 percent versus 16percent), which may partially explain the lower response totreatment observed among African Americans in most clinical trialsof pegylated-interferon and ribavirin.1

About the Phase 3 ADVANCE and REALIZE Studies

ADVANCE was a pivotal Phase 3, randomized, double-blind,placebo-controlled, global study of 1,088 people who were new tohepatitis C treatment. The primary endpoint of ADVANCE was SVR(defined as the proportion of people who had undetectable hepatitisC virus 24 weeks after the end of all treatment; <25 IU/mL,undetectable by Roche COBAS Taqman HCV test). The secondaryendpoint evaluated the safety of telaprevir when dosed incombination with pegylated-interferon and ribavirin.

REALIZE was a pivotal Phase 3, randomized, double-blind,placebo-controlled study conducted globally with the majority ofclinical trial sites in Europe and North America. The study wasdesigned to evaluate the efficacy, safety and tolerability oftelaprevir-based combination regimens in people infected withgenotype 1 chronic hepatitis C who did not achieve a viral cureafter at least one course of prior treatment with interferon-basedtherapy.

Patients were randomized 2:2:1 to two telaprevir-based treatmentarms (simultaneous start and lead-in) and a control arm ofpegylated-interferon and ribavirin alone. The primary endpoint ofthe REALIZE study was SVR in each of the two telaprevir treatmentarms compared to the control arm and for the three groups of peopleincluded in the study.

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: www.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.2Chronic hepatitis C can lead to serious and life-threatening liverproblems, including liver damage, cirrhosis, liver failure or livercancer.2 Though many people with hepatitis C may notexperience symptoms, others may have symptoms such as fatigue,fever, jaundice and abdominal pain.2 Approximately 60percent of people who undergo treatment with an initial 48-weekregimen of pegylated-interferon and ribavirin, the currentlyapproved medicines for genotype 1 hepatitis C, do not achieveSVR,3,4,5 or viral cure.6 If treatment is notsuccessful and a person does not achieve a viral cure, they remainat an increased risk for progressive

liverdisease.7,8

More than 170 million people worldwide are chronically infectedwith hepatitis C.6 In the United States, nearly 4million people have chronic hepatitis C and 75 percent of them areunaware of their infection.9 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.10 Hepatitis C is the leading cause of livertransplantations in the United States and is reported to contributeto 4,600 to 12,000 deaths annually.11,12 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.10

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) Vertex's plan to conduct a studyevaluating a short-duration, 12-week telaprevir-based regimen inpeople how have not been treated for hepatitis C who have the CCvariation of IL28B, (ii) the date of the scheduled meeting of theFDA's Antivirial Advisory Committee and (iii) the FDA's targetreview date for 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 there may

bevarying interpretations of the data from the telaprevir clinicaltrials; that future outcomes from clinical trials of telaprevir maynot be favorable; that future scientific, clinical, competitive orother market factors may adversely affect the potential fortelaprevir-based therapy and the other risks listed under RiskFactors in Vertex's annual report and quarterly reports filed withthe Securities and Exchange Commission and available through

Vertex's website at www.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 www.vrtx.com.

(VRTX - GEN)

1 Ge D, Fellay J, Thomspon AH, et al. Geneticvariation in IL28B predicts hepatitis C treatment-induced viralclearance. Nature. 2009; 461:399-401

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 March 21, 2011.

3 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.

4 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.

5 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.

6 Ghany MG, Strader DB, DL, Seeff, LB.Diagnosis, management and treatment of hepatitis C; An update.Hepatology. 2009;49 (4):1-40.

7 TR, Ghany MG, Kim HY, Snow KK, K,Lok AS. Outcome of sustained virological responders andnon-responders in the Hepatitis C Antiviral Long-Term TreatmentAgainst Cirrhosis (HALT-C) trial. Hepatology. 2008;50(Suppl4):357A (Abstract 115).

8 Veldt BJ, Heathcote J, Wedmeyer H. Sustainedvirologic response and clinical outcomes in patients with chronichepatitis C and advanced fibrosis. ls of Internal Medicine.2007; 147: 677-684.

9 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 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 ofhepatitis C virus (HCV): Costs of a baby boomer epidemic of liverdisease. Available at: http://www.natap.org/2009/HCV/051809_01.htm. Updated May 2009.Accessed March 21, 2011. This report was commissioned by VertexPharmaceuticals, Inc.

11 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.

12 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 Kalmar, 617-444-6992orAmy Pasqua, 617-444-6992orZachry Barber, 617-444-6992mediainfo@...orInvestors: Partridge, 617-444-6108orLora Pike, 617-444-6755or Osborne, 617-444-6057

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