Although the treatment did not work that quickly for all patients, doctors could see whether the three drug regimens selected were going to be successful by just the second day.
The study from Hong Kong, called SODAPI, will be presented at the AASLD “Liver Meeting” in San Francisco. According to the research team, it could lead to substantially reduced time of treatment for hepatitis C virus infection, improved drug accessibility and adherence, low possibility of selecting drug resistant mutants, lower cost, and lower risk of toxicity, according to the research team.
The study, which involved 26 patients, was led by the team of George Lau, MD (HK), FRCP (Lond), FAAASLD, director at the Humanity and Health Medical Centre, in Hong Kong SAR, China. Raymond Schinazi, PhD, DSc, Frances Winship Walters professor of pediatrics at Emory University School of Medicine and senior research career scientist at the Atlanta VA Medical Center (VAMC), was involved in designing the study with his Chinese counterparts.
“We took the three best, most powerful drugs – without regard to manufacturer – and hit the virus with a sledgehammer. And we showed that for some patients, it’s possible to stop treatment after just three weeks, which many thought was impossible,” says Schinazi.
The standard course of antiviral drug treatment for HCV lasts 8-12 weeks. The faster results was achieved by combining FDA-approved drugs that inhibit hepatitis C viral replication, such as sofosbuvir and ledipasvir or daclatasvir, with another type of drug that inhibits the viral protease enzyme: simeprevir or asunaprevir. A similar tactic of combining antiviral drug classes has been used successfully against HIV to control viral infection.
Study participants were all chronically infected by hepatitis C virus genotype 1b, the most common genotype in Asia, and non-cirrhotic. Twenty-seven percent of individuals infected with hepatitis C virus globally are infected with genotype 1b.
“This was a proof of principle study,” Schinazi says. “The next step is to test the same approach on patients with other genotypes and also in more difficult to treat patient groups. Following the concept of response-guided therapy could usher in an era of ultra-short treatment courses for hepatitis C virus. Ideally, it would be great if drug companies work together to find the best and shortest cure combinations.”
Investigators divided the patients into three groups, described below. A “rapid virologic response” (RVR), defined as plasma viral RNA less than 500 international units or IU/ml by day two, was achieved in 18 patients.
- sofosbuvir, ledipasvir, asunaprevir (Harvoni, Sunvepra); RVR in 6/12
- sofosbuvir, daclatasvir, simeprevir (Sovaldi, Daklinza, Olysio); RVR in 6/6
- sofosbuvir, daclatasvir, asunaprevir (Sovaldi, Daklinza, Sunvepra); RVR in 6/8
Patients’ average viral load before treatment was 3.5 million IU/ml. All doses for individual drugs have been FDA-approved based on previous clinical trials.
Under response-guided therapy, the 18 patients who achieved a RVR continued on their regimens for just three weeks. All 18 had a “sustained virologic response”, defined as plasma viral RNA below the limit of detection after 12 weeks, and continue to be monitored. The other patients who didn’t display a RVR continued treatment with Harvoni for 12 weeks (the current standard of care), and they all achieved a sustained virologic response as well. No discontinuations or significant adverse events were reported.
Dr. Schinazi has an equity interest in the manufacturers of two of the drugs in the study.