Opaganib plus standard of care for severe COVID-19 reduces mortality

Opaganib significantly reduced mortality and improved the time to recovery among patients hospitalized for severe COVID-19 who also received remdesivir and corticosteroids, according to a press release from the manufacturer.

“The data collected to date is encouraging and suggests antiviral activity and clinical improvement in some patients based on their level of illness at the time,” Kevin L. Winthrop, MD, MPH, of the Oregon Health & Science University and the global principal investigator in the phase 2 clinical trial of opaganib, told Healio.

Opaganib (Yeliva, RedHill Biopharma Ltd.) is a sphingosine kinase-2 selective inhibitor that has antiviral and anti-inflammatory properties. Researchers evaluated the inhibitor in a phase 2/3 multicenter randomized, double-blind, parallel arm, placebo-controlled study of adult patients with severe COVID-19 pneumonia. The patients were randomly assigned in a 1:1 ratio to receive 500 mg of opaganib or placebo every 12 hours for 14 days on top of remdesivir (Veklury, Gilead Sciences) and corticosteroids, the standard of care, according to the release. They were followed for 28 days after the last administration.

RedHill Biopharma released the results from a prespecified analysis, which showed that patients who received opaganib with standard of care experienced a 70.2% reduction in mortality by day 42. Specifically, the mortality rate was 6.98% for patients in the opaganib plus standard of care arm compared with 23.4% in the placebo plus standard of care arm (P = .034).

A second prespecified analysis showed that opaganib offered significant benefits in the time to recovery, according to the release.

Overall, opaganib improved the median time to viral RNA clearance by at least 4 days, RedHill Biopharma reported. Specifically, participants in the treatment arm achieved median RNA clearance at 10 days compared with 14 days in the placebo arm (P = .043). The treatment was also associated with a 34% increase in the proportion of patients who reached time to recovery by day 14, with 37.4% of patients in the opaganib arm achieving recovery by day 14 compared with 27.9% of patients in the placebo arm, according to the release.

In a post-hoc analysis of 251 patients requiring a Fraction of inspired Oxygen (FiO2) up to and including 60% at baseline, treatment with opaganib was associated with a 62% reduction in mortality and improved outcomes in time to room air, median time to discharge and likelihood of intubation and mechanical ventilation, RedHill Biopharma reported.

“The hospitalized moderate to severe COVID-19 patient group is estimated to represent more than 50% of all hospitalized COVID-19 cases and growing,” Mark Levitt, MD, PhD, chief scientific officer at RedHill Biopharma, said in the release. “The prevalence of omicron, new emerging variants, loss of efficacy of existing drugs against such variants and the difficulty in stopping COVID-19 early enough in its course, despite the availability of new drugs, all point very clearly to the urgent need for new, preferably orally administered, therapeutic options, unaffected by spike protein mutations, for this underserved and substantial patient population.”

RedHill Biopharma told Healio that the company expects opaganib “to exert its effect across variants.”

Moreover, the treatment “has enormous potential to make a significant positive impact on clinical practice for hospitalized patients who otherwise have very limited options,” the company added.

Opaganib has previously received orphan drug designation from the FDA for cholangiocarcinoma and is also being evaluated for advanced cholangiocarcinoma and prostate cancer.

References:

Opaganib, a sphingosine kinase-2 (sk2) inhibitor in covid-19 pneumonia. https://clinicaltrials.gov/ct2/show/NCT04467840. Published July 20, 2021. Accessed Feb. 9, 2022.

Updates on regulatory discussions and plans in multiple countries. https://www.redhillbio.com/news/news-details/2022/RedHill-Biopharmas-Oral-Opaganib-Reduces-Mortality-by-70-Given-on-Top-of-Remdesivir-and-Corticosteroids-in-Severe-COVID-19/default.aspx. Published. Feb. 7, 2022. Accessed Feb. 8, 2022.