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Interim Phase 2 Data Showed Rapid Viral Response to VX-222 in Combination with Telaprevir, Pegylated-Interferon and Ribavirin Among People With Hepatitis C
"Telaprevir triple therapy demonstrated significant improvements in viral cure rates and an ability to halve treatment time to 24 weeks for many people in late-stage studies," said
Using an intent-to-treat analysis, 57 percent (17/30) of people treated with VX-222 (400 mg) in combination with telaprevir, pegylated-interferon and ribavirin had undetectable hepatitis C virus by week two. Among people who were treated with VX-222 (100 mg) in combination with telaprevir, pegylated-interferon and ribavirin, 38 percent (11/29) had undetectable hepatitis C virus by week two. To determine if patients were eligible to stop all treatment at 12 weeks in ZENITH, they had to have undetectable hepatitis C virus at weeks two and eight. Using the eligibility criteria for a 12-week total treatment duration, half (15/30) of the patients in the high-dose VX-222 combination group and 38 percent (11/29) in the low-dose combination group were eligible to stop all treatment at 12 weeks. Ninety percent (27/30) of patients in the high-dose VX-222 group had undetectable hepatitis C virus by week 12 as did 83 percent (24/29) in the low-dose VX-222 group. No viral breakthrough was observed through week 12 among patients receiving the four-drug combinations.
"The early data from this study are encouraging because they showed patients had a very rapid decline in hepatitis C virus as early as the second week of treatment," said
ZENITH is an ongoing Phase 2 study that enrolled 106 people and began with four treatment arms evaluating two-drug and four-drug combination regimens. The primary endpoint is safety and tolerability and the secondary endpoint is on-treatment antiviral activity and the proportion of people in each treatment arm who achieve a sustained viral response (SVR, defined as undetectable hepatitis C virus 24 weeks after the end of treatment). The study is designed to evaluate various combinations of VX-222, telaprevir, pegylated-interferon and ribavirin for the treatment of genotype 1 chronic hepatitis C. In this study, VX-222, telaprevir and ribavirin are given twice daily. Arms A (n=18) and B (n=29) were designed to evaluate the all-oral, two-drug combination regimens of VX-222 (400 mg or 100 mg) and telaprevir (1,125 mg). Both of these study arms were discontinued due to a pre-defined stopping rule related to viral breakthrough. Arms C (n=29) and D (n=30) are ongoing and designed to evaluate the four-drug combination regimens of VX-222 (400 mg and 100 mg), telaprevir (1,125 mg), pegylated-interferon and ribavirin. An additional treatment arm has been added to the study to evaluate an all-oral, three-drug regimen of VX-222, telaprevir and ribavirin in people with genotype 1b chronic hepatitis C. This study arm is now open for enrollment. A sixth and final arm may be added to the trial per protocol based on data from the study.
|ZENITH: Interim Intent to Treat (ITT) Analysis of Arms C and D|
|VX-222 (100 mg) /TVR-|
|based arm(+)||VX-222 (400 mg) /TVR-based arm(++)|
|Week 2 HCV RNA undetectable||38%||57%|
|Week 2 and 8 HCV RNA||38%||50%|
|Week 4 HCV RNA undetectable||86%||87%|
|Weeks 12 HCV RNA||83%||90%|
HCV RNA was evaluated using the TaqMan assay version 2.0.
*As part of a response-guided regimen, people who have undetectable hepatitis C virus at weeks 2 and 8 are eligible to stop all treatment at week 12.
**cEVR, complete early viral response, undetectable hepatitis C virus; evaluated using the Taqman assay version 2.0 (limit of quantification 25 IU/mL)
+VX-222 (100 mg, BID), telaprevir (1,125 mg, BID), Pegasys®(pegylated-interferon alfa-2a) and Copegus® (ribavirin).
++VX-222 (400 mg, BID), telaprevir (1,125 mg, BID), Pegasys®(pegylated-interferon alfa-2a) and Copegus®(ribavirin).
Preliminary Safety and Tolerability
The 12-week safety and tolerability results are preliminary and include data on all patients enrolled in the study: those enrolled in the two-drug (n=47) and four-drug (n=59) treatment arms. The most frequent adverse events observed in this study were mild gastrointestinal symptoms (including diarrhea, nausea and vomiting) and mild fatigue. No patients discontinued due to gastrointestinal symptoms.
Preliminary safety data indicate that there were six discontinuations due to adverse events among the four treatment arms through week 12. There were two serious adverse events considered by the investigator to be potentially related to study medication: acute renal failure (Arm B), which resolved after study medications were discontinued and anemia (Arm C). There was one additional severe adverse event reported of pneumonia, septic shock and renal failure; this severe adverse event was considered by the investigator to be unrelated to study medication. The three additional discontinuations included rash (n=2) and a motor vehicle accident with facial fractures (n=1).
About Telaprevir and VX-222
Vertex has two oral medicines in development for the treatment of genotype 1 chronic hepatitis C: telaprevir and VX-222. Telaprevir is an investigational, oral inhibitor that acts directly on the HCV protease, an enzyme essential for viral replication. To date, more than 2,500 people with genotype 1 chronic hepatitis C have received telaprevir in Phase 2 and Phase 3 studies. Vertex has been granted Priority Review for its applications for the approval of telaprevir by the
Vertex is developing telaprevir in collaboration with Tibotec BVBA and
VX-222 is an investigational, oral, non-nucleoside inhibitor of HCV NS5B polymerase. VX-222 is currently being evaluated in combination with telaprevir, pegylated-interferon and ribavirin in a Phase 2 study. Vertex has worldwide commercial rights for VX-222.
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 Approximately 60 percent of people who undergo treatment of an initial 48-week regimen of pegylated-interferon and ribavirin, the currently approved medicines for genotype 1 hepatitis C, do not achieve SVR,2,3,4 or viral cure.5 If treatment is not successful and a person does not achieve a viral cure, they remain at an increased risk for progressive liver disease.6,7
More than 170 million people worldwide are chronically infected with hepatitis C.5 In
PEGASYS® and COPEGUS® are registered trademarks of Hoffmann-La Roche.
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 potential importance of reducing treatment time to 12 weeks and early data from this study providing new information about the potential to do this with a four-drug VX-222 regimen; (ii) the early data being encouraging because the data showed patients had a very rapid decline in hepatitis C virus as early as the second week of treatment; (iii) the possibility that a sixth treatment arm may be added to the trial; (iv) the date of the scheduled meeting of the FDA's
Vertex creates new possibilities in medicine. Our team aims to discover, develop and commercialize innovative therapies so people with serious diseases can lead better lives.
Vertex scientists and our collaborators are working on new medicines to cure or significantly advance the treatment of hepatitis C, cystic fibrosis, epilepsy and other life-threatening diseases.
Founded more than 20 years ago in
For more information and to view Vertex's press releases, please visit www.vrtx.com.
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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.
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