Merck Announces Results From Phase 2 Study Of Investigational Chronic Hepatitis C Treatment Grazoprevir/Elbasvir In Genotype 1 Infected Treatment-Naïve And Difficult-To-Cure Patients

Merck

, known as MSD outside the United States and Canada, today announced the presentation of results from a multi-arm Phase 2 clinical trial evaluating grazoprevir/elbasvir (MK-5172/MK-8742, the company's investigational NS3/4A protease inhibitor and NS5A inhibitor, respectively) with or without ribavirin (RBV) in treatment-naïve and previously-treated (with peg-interferon/ribavirin [PR]) patients with chronic hepatitis C virus (HCV) genotype 1 (GT1) infection -- the C-WORTHy study (Parts A and B). The final results were presented in oral sessions at the 65th American Association for the Study of Liver Diseases (AASLD) Annual Meeting (also known as The Liver Meeting®) and published as separate papers online in The Lancet. “Merck is committed to developing an efficacious, well-tolerated therapy suitable for a broad spectrum of patients with HCV,” said Dr. Eliav Barr, vice president, infectious diseases, Merck Research Laboratories. “We are encouraged by the findings for grazoprevir/elbasvir in the C-WORTHy trial and look forward to advancing our broad Phase 3 program, which includes hard-to-cure patients that are of the highest need and least studied to date.” Interim results from the C-WORTHy study were presented in April 2014 at the 49th Annual Meeting of the European Association for the Study of the Liver (EASL) and announced by Merck. Results for Treatment-Naïve Cirrhotic Patients and PR Null-Responders The results for HCV mono-infected treatment-naïve GT1 patients with cirrhosis and GT1 prior null-responders with or without cirrhosis treated with grazoprevir/elbasvir, with or without ribavirin, for 12 weeks or 18 weeks are shown in table 1. The rates of sustained viral response,i 12 weeks after the completion of therapy (SVR12) were greater than, or equal to, 90 percent regardless of treatment duration or co-administration of RBV. Table 1 Grazoprevir/ Elbasvir Treatment Duration (wks) Treatment-Naïve Patients with Cirrhosis PR-Nulls With or Without Cirrhosis 12 18 12 18 RBV +RBV -RBV +RBV -RBV + RBV - RBV +RBV -RBV SVR12, n/N Percent [95% CI] 28/31 90% [74, 98] 28/29 97% [82,100] 31/32* 97% [84,100] 29/31 94% [79, 99] 30/32* 94% [79, 99] 30/33 91% [76, 98] 33/33 100% [89, 100] 31/32 97% [84, 100] iiVirologic Failure 3† 1 0 2 0 3 0 1† *1 treatment-naïve patient and 2 PR-null patients were lost to follow-up. †Virologic breakthrough was seen in 1 treatment-naïve patient in the 12-wk +RBV group and in one PR-null patient in the 18-wk -RBV. The rate of virologic failure was five percent (6/123) in treatment-naïve cirrhotic patients and three percent (4/130) in the null-responder population. Treatment was generally well-tolerated. The most common adverse events associated with the administration of grazoprevir/elbasvir in combination with or without RBV were: fatigue (26%), headache (23%) and asthenia (14%). There were no early discontinuations due to adverse events with grazoprevir/elbasvir and no clinically significant abnormalities observed in routinely evaluated biomarkers. Results for HCV Mono-Infected and HIV/HCV Co-Infected Patients Treatment-naïve, non-cirrhotic mono-infected GT1 patients and non-cirrhotic HCV GT1 /HIV co-infected patients treated for 12 weeks with grazoprevir/elbasvir with or without RBV, demonstrated high rates of SVR12, as seen in table 2. Among this patient population treated for 12 weeks, the overall rate of virologic failure was four percent (7/188), including three breakthrough failures and four relapses, in both mono- and co-infected patients. In patients treated for eight weeks, the rate of virologic failure was 17 percent (5/30), with five relapses. The most common adverse events with or without RBV were fatigue (23%), headache (20%), nausea (15%) and diarrhea (10%). There were no early discontinuations due to adverse events with grazoprevir/elbasvir and no clinically significant abnormalities observed in routinely evaluated biomarkers. Table 2 Grazoprevir/ Elbasvir Treatment Duration (wks) HCV Mono-infected HIV/HCV Co-infected 8*** 12 12 12 12 RBV +RBV +RBV -RBV +RBV -RBV SVR12 (n/m) [95% confidence interval] 80% (24/30*) [61, 92] 93% (79/85*) [85, 97] 98% (43/44) [88, 100] 97% (28/29) [82, 100] 87% (26/30*) [69, 96] iiVirologic Failure 5 3**† 1 1 2 * 4 HCV mono-infected patients (1 in the 8-wk and 3 in the 12-wk +RBV arms) and 2 HIV/HCV co-infected patients in the -RBV arm were lost to follow-up. **Virologic breakthrough was seen in 1 patient, which was a new infection with HCV GT2b (or a minor GT2b variant at baseline). ***GT1a patients only. †1 of the patients who relapsed did not receive grazoprevir and received only elbasvir plus RBV for the first month of treatment.