A combination of ravidasvir and sofosbuvir appears to be an effective treatment for chronic hepatitis C virus (HCV) infection across a diverse pool of patients who took part in the first half of the single-arm STORM-C-1 trial underway in Malaysia and Thailand. "HCV affects predominantly vulnerable populations including people using drugs and HIV-coinfected people, who may also be marginalized and discriminated against in access to care," said Dr. Isabelle Andrieux-Meyer of the Drugs for Neglected Diseases initiative, in Geneva, who worked on the study. While direct-acting antivirals (DAA) are an important advancement in HCV treatment, their prohibitive costs have stood in the way of widespread use in many countries, even when generic versions exist. As of 2017, only 5 million or so of the 71 million patients suffering from an HCV infection globally have been treated with DAAs. "To eliminate HCV we need very-easy-to-use DAA combinations, which don't require changes to the HIV treatment, don't require adaptations to the dosage, and don't modify the exposure to other medications, including methadone," Dr. Andrieux-Meyer told Reuters Health by email. Sofosbuvir plus ravidasvir - a pangenotypic non-structural protein 5A (NS5A) inhibitor - is an example of such a combination, Dr. Andrieux-Meyer said. To test this regimen, she and her colleagues enrolled 301 HCV patients in first stage of STORM-C-1, a two-stage, open-label, phase-2/3 single-arm trial taking place in six centers in Malaysia and four centers in Thailand. Half of the participants (52%) had genotype-3 HCV infection, 33% patients had genotype-1a, 9% had genotype-1b, 1% had genotype 2 and 5% had genotype 6. A second stage of the trial including 300 additional patients is currently ongoing. Among the patients in stage 1 of the trial, 27% were already experiencing compensated cirrhosis, 30% had an HIV co-infection and 33% had received previous interferon-based treatment. The trial assessed the efficacy, safety, tolerability, and pharmacokinetics of ravidasvir and sofosbuvir through 12-week and 24-week ribavirin-free regimens. Patients without cirrhosis were prescribed once-daily ravidasvir at 200 mg and sofosbuvir at 400 mg for 12 weeks, while patients with cirrhosis were given the same prescription for 24 weeks. The primary endpoint was an overall sustained virological response at 12 weeks after treatment (SVR12), defined as HCV RNA <12 IU/mL in Thailand and HCV RNA <15 IU/mL in Malaysia. Of the 300 patients in the analysis set, 291 (97%) achieved SVR12. Among the 153 (97%) of 158 patients with genotype-3 infection whos met the SVR12 threshold, a subset of 51 (96%) of the 53 patients who also had cirrhosis within that group did so as well. No difference was found in SVR12 outcomes based on HIV co-infection or a previous interferon treatment. "The 97% cure rate in genotype 3 and genotype 3 cirrhotic subjects, and the 96% cure rate among cirrhotics were wonderful surprises," Dr. Andrieux-Meyer said of the interim analysis, published in The Lancet Gastroenterology and Hepatology. "The need to find a very efficacious, well-tolerated cure with high cure rates in genotype-3 patients and in cirrhotic subjects, and in genotype-3 cirrhotic subjects (the most difficult to treat), was high on our agenda," she added. Despite the high number of comorbidities within the patient population, the ravidasvir-sofosbuvir regimen proved to be well tolerated, safe, and free of any "clinically relevant" drug-drug interactions with the HIV antiretrovirals commonly prescribed in Thailand and Malaysia. The most common adverse events to emerge during the treatments were pyrexia (12%), cough (9%), upper-respiratory-tract infection (8%) and headache (7%). There were no deaths or treatment discontinuations due to the study drugs. "The adverse events are similar to other HCV combinations, both as reported in this trial and in our own experience," said Dr. Imam Waked, professor of medicine and hepatology at Menoufiya University in Egypt and member of the technical advisory board for the Coalition for Global Hepatitis Elimination. "The drug-drug interaction (DDI) results in the study were well documented," Dr. Waked, who was not involved in the research, told Reuters Health by email. "However, they only studied DDIs in patients with HIV and on a few anti-retroviral drugs." He added that "a formal DDI study" might be advisable for this treatment in the future. —Matthew Phelan Source
