VRTX must be desperately hoping that the Telaprevir+VX-222+ribavirin arm generates compelling data because the business proposition of adding VX-222 to Telaprevir+SoC is tenuous at best, IMO.
VRTX Reports Interim Phase-2 Data for Telaprevir+VX-222
[This study originally had four arms, of which two were all-oral arms that were discontinued due to viral breakthrough (#msg-58019192). VRTX the added a fifth arm (i.e. the third arm of those remaining) to test Telaprevir + VX-222 + ribavirin without interferon (#msg-56508419) and this PR says a sixth arm (i.e. the fourth arm of those remaining) may yet be added without any elaboration on what it would be.]
›First study to evaluate four-drug, 12-week treatment duration for hepatitis C
March 31, 2011, 6:30 am EDT
BERLIN--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq:VRTX) today announced interim results from an ongoing Phase 2 study (ZENITH) designed to assess the safety and tolerability of 12-week response-guided treatment regimens with its polymerase inhibitor, VX-222, and its protease inhibitor, telaprevir, in combination with pegylated-interferon and ribavirin in people with genotype 1 chronic hepatitis C who were new to treatment. The study enrolled 106 people into one of four treatment groups. Among those who received VX-222 (400 mg) in combination with telaprevir, pegylated-interferon and ribavirin, interim data showed that 90 percent (27/30) of them had undetectable hepatitis C virus at week 12. Half (15/30) of those in the VX-222 (400 mg) treatment group were eligible to stop all treatment at week 12. People in this same treatment group who were not eligible to stop all treatment at 12 weeks were assigned to receive 24 total weeks of treatment: 12 weeks of the four-drug regimen followed by 12 weeks of pegylated-interferon and ribavirin alone. Preliminary safety results showed that the most frequently reported adverse events were mild gastrointestinal symptoms and mild fatigue. At the time of this analysis, there were no discontinuations due to gastrointestinal symptoms. Data from this study are being presented today at The International Liver Congress™ 2011, the 46th annual meeting of the European Association for the Study of the Liver (EASL) in Berlin, Germany.
“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 Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer for Vertex. “Reducing treatment time in half again to 12 weeks would be another important advance and the early data from this study provide new information about the potential to do this with a four-drug VX-222 regimen.”
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 Adrian Di Bisceglie, M.D., Chief of Hepatology at Saint Louis University School of Medicine. “Hepatitis C virus was undetectable at week 12 of treatment in 90 percent of patients who received the higher dose of VX-222, and half of those in this treatment group were eligible to stop all treatment at that time.”
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[as previously reported]. 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.
[See actual PR for data table.]
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).‹
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