Vertex Announces 12-Week On-Treatment Data and SVR4 From Phase 2 Study of Interferon-Free (All-Oral) Treatment Regimen of INCIVEK®, VX-222 and Ribavirin in People with Genotype 1 Hepatitis C

- Company plans to start Phase 2b study in Q3 2012 to evaluate this interferon-free combination regimen in a total treatment duration as short as 12 weeks -

- Vertex also announces the advancement of its broad portfolio of direct acting antivirals, including its two structurally-distinct nucleotide polymerase inhibitors -

 

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (NASDAQ: VRTX) today announced interim data from two treatment arms of the Phase 2 ZENITH study evaluating an interferon-free (all-oral) treatment regimen of the non-nucleoside polymerase inhibitor VX-222 in combination with INCIVEK ^® (telaprevir) tablets and ribavirin in people with genotype 1a or 1b hepatitis C who were new to treatment. Interim data showed that viral loads were below the lower limit of quantification ( < 25 IU/mL: < LLOQ) for 80 percent (37/46) of patients with genotype 1 hepatitis C at week two and 83 percent (38/46) of patients with genotype 1 at week 12.

ZENITH was designed with strict response-guided criteria that determined whether a patient was eligible to stop all treatment at 12 weeks. Eleven patients met the criteria of having undetectable hepatitis C virus at weeks two and eight of treatment and were therefore eligible to stop all treatment at 12 weeks. Nine of these 11 patients achieved SVR4 (undetectable hepatitis C virus four weeks after the end of all treatment). Data from ZENITH have been submitted for presentation at a medical meeting in the first half of 2012.

Additional interim results from two interferon-free arms of ZENITH announced today showed:

Arm E† (n=23) genotype 1b

Arm F‡ (n=23) genotype 1a

Arms E & F Combined

Week 2

Undetectable HCV RNA*

6/23 (26%)

7/23 (30%)

13/46 (28%)

< LLOQ**

21/23 (91%)

16/23 (70%)

37/46 (80%)

Week 4 (RVR)

Undetectable HCV RNA

21/23 (91%)

13/23 (57%)

34/46 (74%)

< LLOQ

21/23 (91%)

21/23 (91%)

42/46 (91%)

Week 12 (cEVR)

Undetectable HCV RNA

19/23 (83%)

19/23 (83%)

38/46 (83%)

< LLOQ

19/23 (83%)

19/23 (83%)

38/46 (83%)

SVR4

Undetectable HCV RNA

5/5

4/6^

9/11

SVR12

Undetectable HCV RNA

5/5

Data not yet available

Data not yet available

† 19 patients completed 12 weeks of treatment: Two patients discontinued due to adverse events. One patient had virologic failure. One patient withdrew consent. ‡ 20 patients completed 12 weeks of treatment. Two patients had virologic failure. One patient was lost to follow up.   * HCV RNA < 10 IU/mL ** HCV RNA < 25 IU/mL ^ The two patients who did not achieve SVR4 relapsed during the post-treatment follow-up period.

The three drug regimen was generally well-tolerated. The majority of adverse events were reported as mild. There were no cases of moderate or severe rash and no discontinuations due to rash or anemia in the interferon-free study arms. There were two discontinuations due to adverse events in the genotype 1b arm of the study.

Vertex Advances INCIVEK, VX-222 and Ribavirin Combination Regimen
Based on these data, and pending discussions with regulatory agencies, the company intends to pursue a Phase 2b study evaluating multiple interferon-free combination regimens of INCIVEK, VX-222 and ribavirin with total treatment durations as short as 12 weeks in people with genotype 1 (1a and 1b) hepatitis C who are new to treatment. The new study will not use response-guided treatment criteria. If successful, data from this study will be used to design a Phase 3 program with the goal of submitting a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for Vertex's first interferon-free regimen for genotype 1 (1a and 1b) patients by the end of 2014 or beginning of 2015, pending regulatory discussions.

"Since its approval INCIVEK has been used to treat tens of thousands people with hepatitis C and we're committed to further improving the care of those living with this disease by evaluating multiple interferon-free regimens," said Peter Mueller, Ph.D., Executive Vice President, Global Research and Development, and Chief Scientific Officer for Vertex. "Our ultimate goal is to develop well-tolerated, interferon-free treatment regimens with high viral cure rates and short treatment durations for people with hepatitis C. We believe we're well-positioned to achieve this goal by exploring various combinations within our portfolio that includes INCIVEK, VX-222 and two structurally-distinct nucleotide polymerase inhibitors."

Advancing Development of Two Nucleotide Polymerase Inhibitors
As part of a broad strategy to develop interferon-free regimens, Vertex and its collaborator Alios BioPharma are conducting Phase 1 studies of two structurally-distinct nucleotide polymerase inhibitors, known as ALS-2200 and ALS-2158. Vertex announced today that it has begun the first 7-day viral kinetic studies of ALS-2200 and ALS-2158 in people with genotype 1 hepatitis C. Safety and viral kinetic data from these studies are expected in the second quarter of 2012, which could enable the initiation of Phase 2 studies in the second half of 2012 to evaluate multiple interferon-free combination regimens of ALS-2200, ALS-2158, INCIVEK, VX-222 and/or ribavirin.

About ZENITH
ZENITH is an ongoing Phase 2 study that enrolled 152 people with genotypes 1a and 1b chronic hepatitis C who had not been previously treated to evaluate multiple response-guided treatment regimens with VX-222, Vertex's non-nucleoside polymerase inhibitor in development, in different combinations with INCIVEK, Pegasys^® (pegylated-interferon alfa-2a) and Copegus^® (ribavirin), three medicines approved to treat hepatitis C. In all arms, patients were eligible to stop all treatment at 12 weeks if they had undetectable hepatitis C virus at weeks 2 and 8. The primary endpoint of the study is safety and tolerability. The secondary endpoint is on-treatment antiviral activity and the proportion of people in each treatment arm who achieve a sustained viral response.

About INCIVEK and VX-222
INCIVEK ^® (telaprevir) tablets is an oral medicine that acts directly on the hepatitis C virus protease, an enzyme essential for viral replication. INCIVEK is the most prescribed direct-acting antiviral for the treatment of adults with genotype 1 chronic hepatitis C and has been used to treat more than 25,000 people in the United States.

INCIVEK was approved by the U.S. Food and Drug Administration (FDA) in May 2011 and by Health Canada in August 2011 for use in combination with pegylated-interferon and ribavirin for people with genotype 1 chronic hepatitis C with compensated liver disease (some level of damage to the liver but the liver still functions), including cirrhosis (scarring of the liver). INCIVEK is approved for people who are new to treatment, and for people who were treated previously with interferon-based treatment but who did not achieve a sustained viral response, or viral cure (relapsers, partial responders and null responders).

Vertex developed telaprevir in collaboration with Tibotec BVBA and Mitsubishi Tanabe Pharma. Vertex has rights to commercialize telaprevir in North America where it is being marketed under the brand name INCIVEK (in-SEE-veck). Through its affiliate, Janssen, Tibotec has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. In September 2011, telaprevir was approved in the European Union and Switzerland. Telaprevir is known as INCIVO^® in Europe. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries. In September 2011, telaprevir was approved in Japan and is known as Telavic^®.

VX-222 is an oral medicine in development that is a non-nucleoside inhibitor of the HCV NS5B polymerase. Vertex has worldwide commercial rights for VX-222.

About ALS-2200 and ALS-2158
ALS-2200 and ALS-2158 are nucleotide analogues that appear to have a high barrier to drug resistance based on non-clinical and in vitro studies. Both compounds are designed to inhibit the replication of the hepatitis C virus by acting on the NS5B polymerase. Each compound is structurally distinct (adenosine and uracil) and has its own unique mechanism of action, which supports the potential for developing these compounds together as a dual nucleotide regimen and as part of combination therapy regimens, including regimens with INCIVEK and VX-222. Data from in vitro studies showed that both ALS-2200 and ALS-2158 had a synergistic effect when combined together and with INCIVEK and VX-222.

Additionally, in vitro studies of both compounds showed antiviral activity across all genotypes, or forms, of the hepatitis C virus, including genotypes more prevalent outside of the United States.

Vertex gained worldwide rights to ALS-2200 and ALS-2158 through an exclusive worldwide licensing agreement signed with Alios BioPharma, Inc. in June 2011. The agreement also includes a research program that will focus on the discovery of additional nucleotide analogues that act on hepatitis C polymerase. Vertex has the option to select additional compounds for development emerging from the research program.

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