Merck & Co. to submit grazoprevir, elbasvir hepatitis C combination to FDA in 2015

Merck & Co. said Tuesday that it plans to submit a marketing application for its investigational combination regimen consisting of the NS3/4A protease inhibitor grazoprevir and the NS5A inhibitor elbasvir to the FDA in 2015 for the treatment of chronic hepatitis C. The company also reported final results from the Phase II C-WORTHy trial at the American Association for the Study of Liver Diseases (AASLD) annual meeting, with the data additionally published in The Lancet.

The study randomised 471 patients infected with hepatitis C virus (HCV) genotype 1 to receive grazoprevir and elbasvir, with or without ribavirin, for 12 weeks or 18 weeks. The study population consisted of both treatment-naïve patients with cirrhosis and treatment-experienced patients with or without cirrhosis. The primary endpoint was the proportion of patients achieving a sustained virologic response (SVR) after 12 weeks of treatment. Merck reported interim data from the study in April.

Final results for 253 patients demonstrated that treatment with grazoprevir and elbasvir, either with or without ribavirin, was associated with SVR12 rates of 90 percent or greater in both treatment-naïve and -experienced patients, including an SVR12 rate of 100 percent in treatment-experienced patients who were treated for 18 weeks in combination with ribavirin. Meanwhile, rates of virologic failure were 5 percent among treatment-naïve patients and 3 percent in previously treated individuals.

Additionally, Merck reported that the treatment combination was associated with SVR12 rates of 97 percent and 87 percent, respectively, in subjects co-infected with HCV and HIV treated with or without ribavirin. The company observed three cases of virologic failure among co-infected subjects.

The drugmaker stated that no early treatment discontinuations due to adverse events or clinical significant abnormalities in routinely evaluated biomarkers were observed in either mono- or co-infected patients. The most common adverse events associated with treatment with the combination regimen either with or without ribavirin included headache, fatigue and asthenia.

Eliav Barr, vice president of infectious diseases at Merck Research Laboratories, commented "we are encouraged by the findings for grazoprevir/elbasvir in the C-WORTHy trial and look forward to advancing our broad Phase III programme." Earlier this week, the company reported that a four-week treatment course of grazoprevir and elbasvir, in combination with Gilead Sciences' Sovaldi (sofosbuvir), "resulted in sub-optimal efficacy" in treatment-naïve patients with genotype 1 HCV. For related analysis, see Spotlight On: Can Merck & Co. still compete with Gilead in Hepatitis C? – 5 key takeaways from its new data.

For further information on the HCV market, see Payer Insights: Hepatitis C.

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