JIKI trial: Favipiravir shows some benefit in Ebola treatment
SEATTLE — Early results from the JIKI trial in Guinea indicate that favipiravir may reduce mortality rates among patients with Ebola virus and lower viral loads early in their disease course, according to a presentation at CROI 2015.
However, favipiravir (Toyama Chemical Co.) a nucleoside polymerase inhibitor, had no mortality benefit when given to people with high viral loads who also had severe kidney failure.
“Favipiravir is an antiviral drug that is used in severe influenza,” Denis Malvy, MD, of INSERM U897, Université de Bordeaux, France, told Infectious Disease News. “When the Ebola epidemic was progressed, there were many efforts to identify treatment for these patients besides the application of aggressive supportive care. Favipiravir was one of the potential agents because in vitro, the drug showed very powerful activity against the virus, and it demonstrated very encouraging results in small animal models.”
The JIKI trial is a non-comparative, proof-of-concept phase 2 trial being conducted at four centers in Guinea. Patients aged 1 year and older who weigh 10 kg or more were eligible for the study if they had a positive Ebola PCR test. On the first day of treatment, adults received 2,400 mg favipiravir first, then 2,400 mg at hour 8 and 1,200 mg at hour 16. They then received 1,200 mg, twice a day, for 9 days. Children were dosed according to body weight. The primary outcome was mortality at day 14, and cycle threshold (Ct) values recorded for patients on PCR were inversely proportional to the viral loads.
This analysis includes 80 patients: 69 adults and 11 children. Among the adults, 28 patients had Ct values of less than 20 (higher viral loads) and 39 had Ct values of 20 or more (lower viral loads). Most patients (74%) initiated treatment more than 72 hours after the onset of symptoms and most patients (87%) received IV fluids. The mortality rate among the patients with a Ct value of less than 20 was 93%, but the mortality rate among patients with a Ct value of 20 or more was 15%. Among the 15 patients with a Ct value of 25 or more, the mortality rate was 0.
“Early results indicate a signal,” Malvy said. “It brings downs the viral load within 4 days, among the patients that were treated early and had a low viral load to start. That doesn’t mean other patients can’t receive the drug, It means that the drug alone, is not an aggressive standard of care for those patients.
“The message for patients is to receive care as soon as possible. Favipravir would be a backbone for improving the efficacy for early infection, and preventing the evolution of these patients to a more aggressive phase of the disease. There is no magic bullet in this context,” Malvy said.
At the end of January, a data safety monitoring committee reviewed the early data, and determined they were encouraging and should be made public, Malvy said. The study is continuing to enroll patients, and has more than 110 participants so far. He did say that no conclusions can be made yet on the subgroup of children. – by Emily Shafer
Sissoko D. Abstract 103-ALB. Presented at: Conference on Retroviruses and Opportunistic Infections. Feb. 23-26, 2015; Seattle.
Disclosure: Malvy reports no relevant financial disclosures.