Hepatitis C medication development pipeline still strong, with several additional drugs poised for approval.
As we roll into the triple H’s of the summer season (hazy, hot, and humid), it’s already been a banner year for treatment of hepatitis C. Gilead’s Sovaldi is a blockbuster with an astonishing efficacy profile. Its follow-up, Harvoni, also incredibly effective at curing hepatitis C virus (HCV), earlier this year overtook Sovaldi as the top-selling HCV drug, and numerous other medications have shown high safety and effectiveness for patients with both HCV and chronic kidney disease. While cost concerns, insurance coverage concerns, and some safety concerns surround both of those drugs, the overall cure rate is incredibly encouraging.
Now, data from Merck’s C-EDGE study shows than an investigational combination of the protease inhibitor grazoprevir 100 mg and the NS5A inhibitor elbasvir 50 mg — co-formulated by Merck in a single tablet — leads to a sustained virologic response after 12 weeks in almost all patients coinfected with HIV and HCV. On the heels of that news came word that the US Food and Drug Administration (FDA) has granted priority review to grazoprevir/elbasvir.
This once-daily, single-tablet combination was previously granted two breakthrough therapy designations for the treatment of chronic HCV genotype (GT) 4 infection, as well as chronic HCV GT1 infection in end-stage renal disease patients on hemodialysis. Now, the FDA is expected to act on grazoprevir/elbasvir 100 mg/50 mg for the treatment of adult patients infected with chronic HCV GT1, 4 or 6, on January 28, 2016.
The New Drug Application for grazoprevir/elbasvir is partially based on encouraging data from several large, multi-center clinical trials—including C-EDGE, C-SURFER, and C-SALVAGE—which examined the combination treatment with or without ribavirin in HCV GT1, 4 and 6, including patients who were previously treated.
C-EDGE results were reported earlier this year at The International Liver Congress 2015 in Vienna, Austria, and at the 8th International AIDS Society Conference in Vancouver, Canada, last month. The more recent news is that a 12-week follow-up period revealed sustained virologic response—96.3% overall in patients coinfected with HIV and hepatitis. About three-quarters of patients were being treated with tenofovir and about half were being treated with raltegravir. Response rates were slightly lower than the 96.3% rate in the subset of patients whose antiviral regimen contained abacavir (93.6%) or rilpivirine (94.7%). In contrast, sustained virologic response was virtually identical in patients whose antiviral regimen contained tenofovir (97.6%) or raltegravir (96.5%).
Also in that study, the 35 patients with cirrhosis at baseline, the response was 100.0%. This is particularly important because patients with cirrhosis are more difficult to treat. Importantly, the C-EDGE results show that treatment can be effective without ribavirin, which is associated with a number of serious adverse events, including anemia.
The HIV arm of the C-EDGE study is a phase-3, open-label, single-group, multicenter study of 218 treatment-naïve patients infected with HIV and hepatitis C genotypes 1, 4, or 6 (the vast majority [86%] of patients had genotype 1a or 1b. That is just one of several arms of a study is looking at the safety and effectiveness of grazoprevir/elbasvir alone, in combination with other drugs, as a treatment for HCV only, and as treatment for HCV and comorbidities.