A novel combination treatment for hepatitis C virus (HCV) infection—sofosbuvir plus ravidasvir—showed a 97% 12-week cure rate, according to results of a phase II/III clinical trial presented at the International Liver Congress in mid-April 2018 in Paris, France. Investigators from the nonprofit research and development organization Drugs for Neglected Diseases initiative (DNDi) presented the findings and predicted that a 12-week course of treatment would cost approximately US $300 in countries such as Malaysia and Thailand, where the clinical trials are being conducted.
“The results indicate that the sofosbuvir/ravidasvir combination is comparable to the very best hepatitis C therapies available today, but it is priced affordably and could allow an alternative option in countries excluded from pharmaceutical company access programs,” said Bernard Pécoul, MD, MPH, executive director, DNDi, Geneva, Switzerland.
Affordable treatment for HCV is urgently needed in low- and middle-income countries, the investigators explained. The very high prices of direct-acting antivirals (DAAs) and low level of political commitment hinders access to treatment in these countries. To that end, DNDi and its partners developed ravidasvir, an oral NS5A inhibitor with pangenotypic potential, as an affordable DAA for public health use. The drug was licensed to DNDi by Presidio Pharmaceuticals, San Francisco, CA.
Pharco Pharmaceuticals, Alexandria, Egypt, produced ravidasvir for this clinical trial, which took place in 10 sites in Malaysia and Thailand. The trial was managed by DNDi and co-sponsored by the Malaysian Ministry of Health, which set a target price of US $300 for a 12-week treatment—a nearly 100% drop from existing treatment prices in the country.
For this open-label study, 301 adults with chronic HCV infection were treated with the ravidasvir/sofosbuvir combination. At the end of 12 weeks of treatment, 97% achieved sustained virologic response, or SVR (95% CI 94.4-98.6).
Cure rates were high even for the hardest-to-treat subgroups:
- 97% in patients coinfected with HIV
- 96% in patients with liver cirrhosis
- 97% in patients infected with genotype 3
- 96% in genotype 3 patients with cirrhosis
- 96% in patients exposed to previous HCV treatments
The only subgroup in which SVR fell below 96% was in patients with the rare genotype 6, in which the cure rate was 81%.
Médecins Sans Frontières (Doctors Without Borders) has partnered with DNDi to increase access to care and treatment for HCV patients in low- and middle-income countries.
“From a treatment provider perspective, this is very exciting as we have been waiting for a simple, affordable, robust treatment tolerated by all patient groups, including those whose treatment outcomes are currently poorer, like patients under antiretroviral therapy,” said Pierre Mendiharat, deputy operations director, Médecins Sans Frontières. “This will be crucial to expand treatment to the most vulnerable categories of patients in developing countries.”
Investigators are now planning additional clinical trials of sofosbuvir/ravidasvir in patients infected with other HCV genotypes as well as those in particularly vulnerable subgroups.