Prior Non-responders Achieve Treatment Success with Telaprevir plus Pegylated Interferon and Ribavirin

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HIV and Hepatitis.com Coverage of the

45th Annual Meeting of the European

Association for the Study of the Liver (EASL 2010)

April 14 - 18, 2010, Vienna, Austria

Prior Non-responders Achieve Treatment Success with Telaprevir plus Pegylated

Interferon and Ribavirin

SUMMARY: More than half of genotype 1 chronic hepatitis C patients who were

not cured with a previous course of interferon-based therapy achieved sustained

virological response (SVR) when treated with the HCV protease inhibitor

telaprevir plus pegylated interferon and ribavirin, according to a summary

provided by Vertex Pharmaceuticals of a study presented this week at the 45th

Annual Meeting of the European Association for the Study of the Liver (EASL

2010) in Vienna. Response varied according to type of previous treatment

failure; while almost all prior relapsers achieved SVR, prior null responders

had the lowest odds of successful treatment.

By Liz Highleyman

Below is an edited excerpt from a Vertex press release describing findings from

Study 107, an open-label rollover study of control patients from the PROVE

trials. (Final data from PROVE 3 were recently published.)

The EASL abstract -- which includes less complete data than the oral

presentation -- can be viewed online:

http://www.kenes.com/easl2010/Orals/108.htm

59 Percent of Patients Overall Achieved SVR with

Telaprevir-Based Regimens in Study 107 After Not

Achieving SVR with at Least One Prior Course of

Treatment for Hepatitis C Virus Infection

56% of prior treatment null responder patients achieved SVR with a 48-week

telaprevir-based regimen

97% of prior treatment relapsers and 55% of prior treatment partial responders

achieved SVR with 24-week or 48-week telaprevir-based regimens

Vienna -- April 15, 2010 -- In conjunction with an oral presentation at the 45th

Annual Meeting of the European Association for the Study of the Liver (EASL) in

Vienna, Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced that

59 percent of patients overall who received a telaprevir-based combination

regimen in Study 107 achieved a sustained viral response (SVR) after failing to

achieve SVR with a least one prior course of treatment for hepatitis C virus

(HCV) infection. Specifically, 56% of prior treatment null responders (n=27)

achieved SVR after treatment with a 48-week telaprevir-based combination

regimen, and 97% of prior treatment relapsers (n=29) and 55% of prior treatment

partial responders (n=29) achieved SVR after treatment with a 24-week or 48-week

telaprevir-based combination regimen. Ten patients (9%, n=117) discontinued all

therapy due to adverse events, with rash being the most common reason for

discontinuation.

Study 107 was an open-label Phase 2 rollover study of patients who did not

achieve SVR after receiving pegylated interferon (Peg-IFN) and ribavirin (RBV)

in the control arms of the Phase 2 PROVE trials of telaprevir. Telaprevir is an

investigational oral HCV protease inhibitor being developed by Vertex in

collaboration with Tibotec and Mitsubishi Tanabe Pharma. A Phase 3 registration

program for telaprevir is nearing completion, in both treatment-naive and

treatment-failure HCV patients. The Phase 3 REALIZE trial is evaluating a

48-week telaprevir-based treatment regimen in treatment-failure patients,

including null responder patients. In the second half of 2010, Vertex plans to

submit a New Drug Application to the U.S. Food and Drug Administration (FDA) for

telaprevir for both treatment-naive and treatment-failure patients.

" The majority of genotype 1 patients who undergo their first regimen of

pegylated-interferon and ribavirin fail to achieve SVR and are left with few

options for subsequent re-treatment of their disease, " said Berg, MD,

Medical Development, Hepatology Section, University Clinic, Leipzig, Germany.

" Treatment with telaprevir-based regimens in Study 107 resulted in an overall

SVR rate of 59 percent across all patients enrolled in the study, with 56

percent of the most difficult-to-treat null responder patients achieving SVR

with a 48-week telaprevir-based regimen. "

" Study 107 provided important insight into the potential future use of

telaprevir-based regimens in the treatment of patients who failed to respond to

currently approved therapies, " said Kauffman, MD, PhD, Vertex's Senior

Vice President, Clinical Development and Chief Medical Officer. " Based on

information generated in Study 107, as well as data from the PROVE 3 clinical

trial, we believe that a 48-week treatment regimen may increase the likelihood

that certain treatment-failure patients are able to achieve SVR. In our Phase 3

REALIZE trial in treatment-failure patients, we are evaluating a 48-week

treatment regimen and are currently awaiting final SVR results, which we expect

in the third quarter. "

Study 107 Design and Results

Study 107 was an open-label, Phase 2 rollover study of telaprevir in combination

with Peg-IFN and RBV in patients who had previously received treatment with

Peg-IFN and RBV in the control arms of either of the PROVE 1, PROVE 2 or PROVE 3

trials, and did not achieve SVR. Patients in Study 107 were well-characterized

as null responders, partial responders, relapsers or breakthroughs, based on

their antiviral response documented as a result of their participation in the

control arms of the PROVE clinical trials.

When Study 107 began, all patients were to receive 12 weeks of telaprevir in

combination with Peg-IFN and RBV followed by an additional 12 weeks of Peg-IFN

and RBV, for a total of 24 weeks of therapy. Stopping rules required any patient

who did not achieve HCV RNA of 25 IU/mL or less by week 4 to stop all treatment.

In 2008, Study 107 was amended and underwent several changes, most notably to

the duration of treatment. The changes to treatment duration in Study 107 were

aimed at providing patients with a higher likelihood of achieving SVR. Following

the amendments, only patients who did not achieve HCV RNA of 100 IU/mL or less

at week 4 were required to stop therapy. In addition, prior treatment null

responder patients were to receive a 48-week telaprevir-based treatment regimen.

Patients with prior treatment relapse, prior treatment viral breakthrough and

prior treatment partial response were eligible to receive a response-guided

24-week telaprevir-based treatment regimen if they achieved undetectable HCV RNA

at week 4 and 12, otherwise these patients would receive a 48-week regimen.

A total of 117 patients enrolled in Study 107, including 51 patients with prior

treatment null response, 29 patients with prior treatment partial response, 8

patients with prior treatment viral breakthrough, and 29 patients with prior

treatment relapse.

An overall SVR rate of 59 percent and an overall relapse rate of 16 percent were

observed in Study 107. Sustained viral response rates for each arm of Study 107

are as follows:

Study 107 Safety and Tolerability

Adverse events reported in Study 107 were similar to those reported in prior

Phase 2 trials of telaprevir. The most common adverse events reported were rash

(all types), fatigue, pruritus, and headache. Discontinuation of all therapy due

to adverse events occurred in 10 patients (9%; n=117), with rash being the most

common reason for discontinuation.

About Telaprevir

Telaprevir is an investigational, oral inhibitor of HCV protease, an enzyme

essential for viral replication, and is being evaluated as part of a global

Phase 3 registration program in more than 2,200 treatment-naive and

treatment-failure patients. Vertex is collaborating with Tibotec and Mitsubishi

Tanabe Pharma to develop telaprevir. Vertex retains commercial rights to

telaprevir in North America. Tibotec has rights to commercialize telaprevir in

Europe, South America, Australia, the Middle East and other countries.

Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and

certain Far East countries.

About Vertex

Vertex Pharmaceuticals Incorporated is a global biotechnology company committed

to the discovery and development of breakthrough small molecule drugs for

serious diseases. The Company's strategy is to commercialize its products both

independently and in collaboration with major pharmaceutical companies. Vertex's

product pipeline is focused on viral diseases, cystic fibrosis, inflammation,

autoimmune diseases, epilepsy, cancer, and pain.

For further information, see www.vrtx.com.

Investigator affiliations: University Clinic, Leipzig, Leipzig, Germany; Duke

University Medical Center, Durham, NC; Vertex Pharmaceuticals Incorporated,

Cambridge, MA; Cedars-Sinai Medical Center, Los Angeles, CA; Bon Secours Health

System, Liver Institute of Virginia, Newport News, VA; University of Vienna,

Vienna, Austria; University of Toronto, Toronto, Ontario, Canada; Hôpital Henri

Mondor, Créteil, France; Johann Wolfgang Goethe University Medical Center,

furt/Main, Germany; Academisch Medical Center, University of Amsterdam,

Amsterdam, Netherland; Royal Free and University College School of Medicine,

London, UK.

4/16/10

Source

Vertex Pharmaceuticals. 59 Percent of Patients Overall Achieved SVR with

Telaprevir-Based Regimens in Study 107 After Not Achieving SVR with at Least One

Prior Course of Treatment for Hepatitis C Virus Infection. Press release. April

15, 2010.

ReferenceT Berg, JG Mchutchison, N Adda, and others. SVR with telaprevir,

peginterferon alfa-2a and ribavirin in HCV patients with well-characterized

prior null response, partial response, viral breakthrough or relapse after PR.

45th Annual Meeting of the European Association for the Study of the Liver (EASL

2010). Vienna, Austria. April 14-18, 2010. (Abstract).