Positive Interim Data From a Phase 2 Study of INCIVEK™ (telaprevir) Combination Therapy in People Co-Infected with Hepatitis C and HIV Presented at The Liver Meeting®
- Data showed 74% of people had undetectable hepatitis C virus 24 weeks after starting INCIVEK combination treatment -
- Vertex to initiate Phase 3 study to evaluate 24- and 48-week treatment durations in people who are co-infected -

SAN FRANCISCO--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced positive interim results from an ongoing Phase 2 study designed to evaluate the safety and tolerability of INCIVEK™ (telaprevir) tablets in combination with pegylated-interferon and ribavirin in people who are co-infected with chronic genotype 1 hepatitis C (HCV) and human immunodeficiency virus (HIV). Data showed 74 percent (28/38) of patients who were treated with INCIVEK (in-SEE-veck) combination therapy had undetectable hepatitis C virus (HCV RNA) at Week 24 of treatment compared to 55 percent (12/22) who were treated with pegylated-interferon and ribavirin alone. Changes in CD4 counts were similar between the treatment groups and no HIV viral load breakthroughs were observed in either treatment group during the study. Adverse events that occurred more frequently (≥10 percent difference) in the INCIVEK arms compared to placebo were abdominal pain, vomiting, nausea, fever, dizziness, depression and itchiness. No severe rashes were reported through 24 weeks. Interim results from this study are being presented at The Liver Meeting®, the 62nd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), November 4-8, 2011 in San Francisco.

"Treating hepatitis C in people who also have HIV is particularly challenging as only about 30 percent of people clear the virus after undergoing nearly a year of treatment with currently available medicines," said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer at Vertex. "As we prepare for our new Phase 3 study to evaluate INCIVEK combination therapy in a much larger group of people who are co-infected, data from this study give us hope that in the future we'll be able to help more co-infected patients clear the virus."

There are two parts to this study: Part A is evaluating people who are not currently being treated with antiretroviral therapy for HIV infection and Part B is evaluating those who are taking an Atripla® or Reyataz®-based regimen for HIV. This study enrolled patients who were new to hepatitis C treatment. Interim data also showed 63 percent (24/38) of patients treated with INCIVEK combination therapy in this study had an extended rapid hepatitis C viral response (eRVR, measured as undetectable HCV RNA at weeks 4 and 12 of treatment) compared to approximately 5 percent (1/22) who received pegylated-interferon and ribavirin alone.

"Complications associated with hepatitis C such as scarring of the liver typically develop much faster in people infected with both hepatitis C and HIV," said Kenneth Sherman, M.D., Ph.D., Professor of Medicine at the University of Cincinnati College of Medicine, Director of the Division of Digestive Diseases for UC Health and Principal Investigator of the trial. "As HIV treatments have improved, liver disease associated with hepatitis C has become a leading cause of death among people who are co-infected, so offering patients a better chance at a cure for hepatitis C while maintaining their suppression of HIV would be a major advance in treatment."

Interim Study Results

Sixty-two people were enrolled in this Phase 2 study and 60 received at least one dose of study drug. This analysis was conducted when all patients had reached week 24 of study treatment (n=44). Sixteen patients discontinued prior to week 24 of study treatment. Reasons for study discontinuation include: meeting a predefined stopping rule (n=6), lost to follow-up (n=1), discontinuation due to hemolytic anemia (n=1), withdrawal of consent (n=2), non-compliance (n=4) and other reasons (n=2).

24-Week On-Treatment Interim Analysis

Part A(No ART) Part B Atripla® Part BReyataz®-based regimen Total
TVR- based Arm+ Control Arm++ TVR-based Arm+ Control Arm++ TVR-based Arm+ Control Arm++ TVR-based Arm+ Control Arm++

RVR* 71% (5/7) 0% (0/6) 75% (12/16) 12% (1/8) 60% (9/15) 0% (0/8) 68% (26/38) 4.5% (1/22)
eRVR** 57% (4/7) 0% (0/6) 75% (12/16) 12% (1/8) 53% (8/15) 0% (0/8) 63% (24/38) 4.5% (1/22)
Week 24 Undetectable 86% (6/7) 33% (2/6) 75% (12/16) 50% (4/8) 67% (10/15) 75% (6/8) 74% (28/38) 55% (12/22)
Atripla (efavirenz, tenofovir disoproxil fumarate and emtricitabine): TVR was dosed at 1,125 mg, every 8 hours (q8h).

Reyataz-based regimen (ritonavir-boosted atazanavir, tenofovir disoproxil fumarate and emtricitabine or lamivudine): TVR was dosed at 750 mg, every 8 hours (q8h).

*RVR: rapid viral response; undetectable (<25IU/mL undetectable by Roche COBAS Taqman HCV test) at week 4.

**eRVR: early viral response; undetectable (<25IU/mL undetectable by Roche COBAS Taqman HCV test) at weeks 4 and 12.

+12 weeks of telaprevir (TVR), Pegasys® (PEG, pegylated-interferon alfa-2a) and Copegus® (RBV, ribavirin) followed by 36 weeks of only PEG and RBV.

++48 weeks of PEG and RBV only for hepatitis C treatment.


Interim Safety Results

The majority of adverse events in this study were mild or moderate. Adverse events that occurred more frequently (≥10 percent difference) in the INCIVEK arms compared to placebo were abdominal pain, vomiting, nausea, fever, dizziness, depression and itchiness. No severe rashes were reported through 24 weeks. Hyper-bilirubinemia occurred more frequently among patients treated with INCIVEK combination therapy who were also taking a Reyataz-based regimen for the treatment of HIV. Hyper-bilirubinemia is a known side effect of Reyataz-based regimens. Three patients who received INCIVEK combination therapy experienced an adverse event (gall stones, jaundice, hemolytic anemia), all occurring in Part B, that led to discontinuation of one or more study drugs.

About the Ongoing Phase 2 Study

This study is a Phase 2, two-part (A and B), randomized, double-blind, placebo-controlled, parallel group, multi-center study in people chronically infected with both genotype 1 hepatitis C virus and human immunodeficiency virus (HIV) who were new to hepatitis C treatment. The study enrolled 62 people. The primary endpoint of the study is to evaluate the safety and tolerability of telaprevir-based combination therapy in people co-infected with hepatitis C and HIV. A secondary endpoint is to evaluate rates of sustained viral response (SVR, or cure). The study is being conducted by Vertex in collaboration with Tibotec BVBA.

People in Part A and Part B of the study were randomized to receive either 12 weeks of telaprevir or placebo in combination with peginterferon alfa-2a (Pegasys®) and ribavirin (Copegus®) followed by 36 weeks of peginterferon alfa-2a and ribavirin alone. Part A (n=13) of the study enrolled people who were not receiving antiretroviral therapy (ART) for the treatment of HIV. Part B (n=47) enrolled people who were being treated for HIV with either Atripla (n=24) or a Reyataz-based regimen (n=23). For people in Part B who were receiving Atripla, telaprevir was dosed at 1,125 mg every eight hours (q8h) based on data from a drug-drug interaction study. For people in Part B who were receiving a Reyataz-based regimen, telaprevir was dosed at 750 mg every eight hours (q8h). The ART regimens evaluated in this study were selected based on current HIV treatment guidelines from the U.S. Department of Health and Human Services and International AIDS Society and drug-drug interaction studies of INCIVEK and commonly used ART medicines.

Vertex's planned Phase 3 study is expected to begin enrollment by the end of 2011. The study will evaluate 24- and 48-week response-guided regimens of INCIVEK combination therapy in people co-infected with hepatitis C and HIV who are new to treatment for hepatitis C or relapsed after at least one prior course of therapy with pegylated-interferon and ribavirin alone. Patients who had not responded to a prior course of treatment (partial responders and nulls) will receive 48 total weeks of INCIVEK-based treatment.

About INCIVEK

INCIVEK 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 genotype 1 chronic hepatitis C and has been used to treat more than 17,000 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 people with genotype 1 chronic hepatitis C (mono-infection) with compensated liver disease (some level of damage to the liver but the liver still functions), including cirrhosis (scarring of the liver). INCIVEK combination therapy is approved for people 18 and older who are new to treatment, and for people who were treated previously but who did not achieve a sustained viral response or viral cure (relapsers, partial responders and null responders).

INCIVEK (750 mg) is given as two 375 mg tablets three times daily for 12 weeks in combination with pegylated-interferon and ribavirin. Each monthly package of INCIVEK contains four weekly boxes that include daily blister strips. After the first 12 weeks, all patients stop receiving INCIVEK and continue treatment with pegylated-interferon and ribavirin alone for an additional 12 weeks or 36 weeks of treatment. With INCIVEK combination therapy, more than 60 percent of people treated for the first time, as well as those who relapsed after previous therapy, are expected to complete all treatment in 24 weeks. All other patients receive a total of 48 weeks of treatment. A Phase 3 study evaluating twice-daily dosing of INCIVEK is ongoing.

Rash and anemia are the most serious side effects associated with INCIVEK, which led to treatment discontinuation in about 1 percent of people in clinical studies. The most common side effects reported with INCIVEK combination treatment include fatigue, itching, nausea, diarrhea, vomiting, anal or rectal problems, and taste changes.

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 will be known as Telavic®.

IMPORTANT SAFETY INFORMATION

Indication

INCIVEK™ (telaprevir) is a prescription medicine used with the medicines peginterferon alfa and ribavirin to treat chronic (lasting a long time) hepatitis C genotype 1 infection in adults with stable liver problems, who have not been treated before or who have failed previous treatment. It is not known if INCIVEK is safe and effective in children under 18 years of age.

Important Safety Information

INCIVEK should always be taken in combination with peginterferon alfa and ribavirin. Ribavirin may cause birth defects or death of an unborn baby. Therefore, a patient should not take INCIVEK combination treatment if she is pregnant or may become pregnant, or if he is a man with a sexual partner who is pregnant. Patients must use two forms of effective birth control during treatment and for the 6 months after treatment with these medicines.

INCIVEK and other medicines can affect each other and can also cause side effects that can be serious or life threatening. There are certain medicines patients cannot take with INCIVEK combination treatment. Patients should tell their healthcare providers about all the medicines they take, including prescription and non-prescription medicines, vitamins and herbal supplements.

INCIVEK can cause serious side effects including rash and anemia. The most common side effects of INCIVEK include itching, nausea, diarrhea, vomiting, anal or rectal problems, taste changes and tiredness. There are other possible side effects of INCIVEK, and side effects associated with peginterferon alfa and ribavirin also apply to INCIVEK combination treatment. Patients should tell their healthcare providers about any side effect that bothers them or doesn't go away.

Please see full Prescribing Information for INCIVEK including the Medication Guide, available at www.INCIVEK.com.

INCIVEK™ is a trademark of Vertex Pharmaceuticals Incorporated.

PEGASYS® and COPEGUS® are registered trademarks of Hoffmann-La Roche.

About Hepatitis C

Hepatitis C is a serious liver disease caused by the hepatitis C virus, which is spread through direct contact with the blood of infected people and ultimately affects the liver.1 Chronic hepatitis C can lead to serious and life-threatening liver problems, including liver damage, cirrhosis, liver failure or liver cancer.1 Though many people with hepatitis C may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.1

Unlike HIV and hepatitis B virus, chronic hepatitis C can be cured.2 However, approximately 60 percent of people do not achieve SVR,3,4,5 or viral cure,6 after treatment with 48 weeks of pegylated-interferon and ribavirin alone. If treatment is not successful and a person does not achieve a viral cure, they remain at an increased risk for progressive liver disease.7,8

More than 170 million people worldwide are chronically infected with hepatitis C.6 In the United States, nearly 4 million people have chronic hepatitis C and 75 percent of them are unaware of their infection.9 Hepatitis C is four times more prevalent in the United States compared to HIV.9 The majority of people with hepatitis C in the United States were born between 1946 and 1964, accounting for two of every three people with chronic hepatitis C.10 Hepatitis C is the leading cause of liver transplantations in the United States and is reported to contribute to 4,600 to 12,000 deaths annually.11,12 By 2029, total annual medical costs in the United States for people with hepatitis C are expected to more than double, from $30 billion in 2009 to approximately $85 billion.9

About Hepatitis C and HIV Co-Infection

There are 1 million people living with HIV in the United States, and an estimated 300,000 people living with HIV/AIDS in the United States are also infected with hepatitis C.13 There have been dramatic improvements in the treatment of HIV and the prognosis for people living with HIV. However, liver disease progresses more rapidly in people co-infected with hepatitis C and HIV, with an increased rate of progression to cirrhosis, decompensated liver disease, hepatocellular carcinoma and death. 14,15,16,17 The hepatitis C cure rate for with a 48-week treatment of pegylated-interferon and ribavirin, the current standard of care for people with co-infection, is approximately 29 percent.18

Special Note Regarding Forward-Looking Statements

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including statements regarding (i) the hope that in the future Vertex will be able to help more co-infected patients clear the virus; (ii) the possibility that co-infected patients could have a better chance at a cure for hepatitis C while maintaining their suppression of HIV; and (iii) the plan to begin enrollment in a Phase 3 study in people who are co-infected by the end of 2011. While the company believes the forward-looking statements contained in this press release are accurate, there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, that future scientific, clinical, competitive or other market factors may adversely affect the potential for INCIVEK-based therapies; that the interim data presented in this press release may not be predictive of the final outcomes from this Phase 2 clinical trial; that the outcomes from future clinical trials of INCIVEK-based therapies in co-infected patients may not be favorable and the other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through Vertex's website at www.vrtx.com. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.