Nov 4 2013
Interim data presented today show that all patients (13/13) who reached their 4-week post-treatment follow-up have undetectable levels of hepatitis C virus (SVR4) after completing a 12-week regimen of faldaprevir, deleobuvir, PPI-668 and ribavirin. These data from Boehringer Ingelheim’s ongoing Phase II collaborative trial with Presidio Pharmaceuticals will be presented on Monday during the ‘Late-Breaking Posters’ session at the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), taking place in Washington, D.C. Additional data from the trial show 100% of patients (12/12) treated with a ribavirin-free regimen had hepatitis C virus (HCV) levels below the lower level of quantification at 4 weeks. Safety and tolerability appears to be better in this ribavirin-free treatment arm compared to those with ribavirin.
“These interim results add to the growing body of evidence for faldaprevir as an effective treatment for a broad range of genotype-1 infected hepatitis C patients, including the more difficult-to-cure. The trial is still in the early stages but the initial results look promising,” said Professor Klaus Dugi, Senior Vice President of Medicine at Boehringer Ingelheim. “These data further demonstrate the future potential of faldaprevir as the foundation of interferon-free treatment regimens. Our pivotal HCVerso® studies which investigate the interferon-free regimen of faldaprevir, deleobuvir and ribavirin are currently in Phase III development. We look forward to the final results from both trials in Q2 next year.”
The ongoing Phase II trial features the 12-week regimen both with and without ribavirin in 36 genotype-1a infected patients, one of the more difficult-to-cure types of hepatitis C virus. In addition, more than half the patients in the study (20/36) had pre-existing HCV mutations. This includes the Q80K variant which is common in genotype-1a infected patients and has been associated with reduced responses to some HCV protease inhibitors. Notably, all 12 patients in the study with pre-existing Q80K mutations are responding well to treatment with the faldaprevir-based interferon-free regimen.
To date, all patients in the study have received at least 4 weeks of treatment and 97% (35/36) achieved HCV levels below the lower limit of quantification at week 4. One patient had an initial virologic response but then exhibited viral breakthrough and was discontinued after 5 weeks of treatment. Overall, adverse events in the study have been mild to moderate, with the incidence and severity of skin rashes and gastrointestinal side effects similar to those observed in previous trials studying faldaprevir and deleobuvir.
Overview of Boehringer Ingelheim’s HCV trial programme
Boehringer Ingelheim’s hepatitis C clinical trial programme includes a broad range of genotype-1 infected patients. The programme features three treatment regimens, with faldaprevir as the foundation:
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Study
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Regimen
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Population
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Status
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STARTVerso™
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Faldaprevir pegylated interferon, ribavirin
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GT-1 , TN, TE, HCV/HIV co-infection, advanced liver disease
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Regulatory submissions pending
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HCVerso®
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Faldaprevir, deleobuvir, ribavirin
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GT-1b, TN, TE, advanced liver disease
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Phase III results expected Q2 2014
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Presidio collaboration
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Faldaprevir, deleobuvir, PPI-668 +/- ribavirin
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GT-1a, TN, non-cc IL28B
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Phase II final results expected Q2 2014
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An individualised approach to hepatitis C
The breadth of patients studied in Boehringer Ingelheim’s hepatitis C trial programme reflects a population that physicians see in the clinic, including those with difficult types of hepatitis C virus to cure.
“The huge diversity between hepatitis C patients, due to differing personal factors and variations in the virus, highlight the importance of an individualised approach to treatment,” said Graham Foster, Professor of Hepatology, Queen Mary’s, London. “The difference between HCV genotypes is substantial. For example, genotype-1a and 1b share only around 70% of the same genetic material which is more distant than the genetic similarity between humans and some other animals and patients have differing degrees of liver damage that may require changes to the therapeutic approach. Given the diversity of the disease and the virus it is likely that each patient will need to be assessed on an individual basis and the best treatment assigned accordingly.”
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