Opaganib in COVID-19 pneumonia: Results of a randomized, placebo-controlled Phase 2a trial

Rationale: Opaganib, an oral sphingosine kinase-2 inhibitor with antiviral and anti-inflammatory properties, was shown to inhibit SARS-CoV-2 replication in vitro. We thus considered that opaganib could be beneficial for moderate to severe COVID-19 pneumonia. Objectives: To evaluate the effect of opaganib on supplemental oxygen requirements, time to hospital discharge and its safety in COVID-19 pneumonia hospitalized patients requiring supplemental oxygen. Methods: This Phase 2a, randomized, double-blind, placebo-controlled study, was conducted between July and December 2020 in eight sites in the USA. Forty-two enrolled patients received opaganib (n=23) or placebo (n=19) added to standard of care for up to 14 days and were followed up for 28 days after their last dose of investigational product. Main Results: By Day 14, 50.0% of patients in the opaganib and 22.2% in the placebo group no longer required supplemental oxygen for at least 24 hours, while 86.4% and 55.6%, respectively, were discharged from hospital. The relative decrease in total supplemental oxygen requirement from baseline to Day 14 was 61.6% in the opaganib versus 46.7% in the placebo arms. The incidence of [≥] Grade 3 treatment-emergent adverse events was 17.4% and 33.3% in the opaganib and placebo groups, respectively. Three deaths occurred in each group. Conclusions: In this proof-of-concept study, patients receiving oral opaganib required less supplemental oxygen, resulting in earlier hospital discharge, with no safety concerns arising. These findings support further evaluation of opaganib in this population.