Merck known as MSD outside of the United States and Canada, has announced the first sustained virologic response (SVR) results 12 weeks after completion of therapy (SVR12, considered virologic cure) from C-SURGE, an ongoing, open label phase 2 clinical trial evaluating MK-3682B [uprifosbuvir (MK-3682)2/grazoprevir3/rusazvir4], the company’s investigational triple-combination therapy in treatment-experienced patients with hepatitis C virus (HCV) genotype (GT) 1 infection for whom treatment with approved direct-acting antiviral regimens had failed. The study showed that 100 percent (43/43) of patients who completed 16 weeks of treatment plus ribavirin (RBV) achieved SVR12 and 100 percent (49/49) of patients who completed 24 weeks of treatment achieved SVR12 (abstract PS-159). These results will be presented today at The International Liver Congress 2017.
“Despite the significant progress made to address the worldwide epidemic of chronic hepatitis C infection, there remains a need for additional treatment options,” said Dr. Heiner Wedemeyer, lead study investigator and research group leader in the department of gastroenterology, hepatology and endocrinology at Hannover Medical School, Germany. “We are encouraged by the high virologic cure rates in the difficult-to-treat patients observed in the C-SURGE study and look forward to further evaluation of this investigational triple-combination therapy.”
The phase 2 C-SURGE study enrolled 94 patients who were randomized to receive a once-daily regimen of MK-3682B for either 16 weeks with RBV (n=45) or 24 weeks without RBV (n=49); one patient in the 16-week arm withdrew prior to starting treatment. Of the 93 patients who received treatment (full analysis set), 57 had previously received a regimen of ledipasvir/sofosbuvir (LDV/SOF) for 12 to 24 weeks, 14 had previously received LDV/SOF for 8 weeks and 22 had previously received ZEPATIER (elbasvir and grazoprevir) for 12 weeks. Seventy-eight patients who received treatment had at least one baseline NS5A resistance-associated substitution (RAS) at positions 28, 30, 31 or 93. Eighty patients who received treatment in C-SURGE had GT1a infection, and 40 patients had compensated cirrhosis. In the full analysis set, 98 percent of patients who received MK-3682B for 16 weeks with RBV (43/44) and 100 percent of patients who received MK-3682B for 24 weeks without RBV (49/49) achieved SVR12.
Results from the modified full analysis set, which excludes one patient in the 16-week arm who withdrew after three doses of treatment, show that 100 percent of patients receiving treatment with MK-3682B for 16 weeks with RBV (43/43) and 100 percent of patients receiving treatment with MK-3682B for 24 weeks without RBV (49/49) achieved SVR12.
Across the combined treatment arms, the most common adverse events (AEs) reported in the full analysis set were fatigue (35%), headache (13%), diarrhea (9%), rash (9%) and pruritus (5%). There were no drug-related serious AEs, and no patients discontinued treatment due to a drug-related AE.
SVR8 results from the C-SURGE study were previously presented at The Liver Meeting 2016.