ABSTRACT
Rationale There are few treatment options for severe COVID-19 pneumonia. Opaganib is an oral treatment under investigation. Objective Evaluate opaganib treatment in hospitalized patients with severe COVID-19 pneumonia. Methods A randomized, placebo-controlled, double-blind phase 2/3 trial was conducted in 60 sites worldwide from August 2020 to July 2021. Patients received either opaganib (n=230; 500mg twice daily) or matching placebo (n=233) for 14 days. Main Outcome Measurements Primary outcome was the proportion of patients no longer requiring supplemental oxygen by day 14. Secondary outcomes included changes in the World Health Organization Ordinal Scale for Clinical Improvement, viral clearance, intubation, and mortality at 28- and 42-days. Main Results Pre-specified primary and secondary outcome analyses did not demonstrate statistically significant benefit (except for time to viral clearance). Post-hoc analysis revealed the fraction of inspired oxygen (FiO2) at baseline was prognostic for opaganib treatment responsiveness and corresponded to disease severity markers. Patients with FiO2 levels at or below the median value ([≤]60%) had better outcomes after opaganib treatment (n=117) compared to placebo (n=134). The proportion of patients with [≤]60% FIO2 at baseline that no longer required supplemental oxygen (at least 24 hours) by day 14 of opaganib treatment increased (76.9% vs 63.4%: p-value =0.033). There was a 62.6% reduction in intubation/mechanical ventilation (6.84% vs 17.91%; p-value=0.012) and a clinically meaningful 62% reduction in mortality (5.98% vs 16.7%; p-value=0.019) by day 42. No new safety concerns observed. Conclusions Post-hoc analysis supports opaganib benefit in COVID-19 severe pneumonia patients that require lower supplemental oxygen ([≤]60% FiO2). Further studies are warranted.
Subject(s)
COVID-19 , Pneumonia , Severe Acute Respiratory SyndromeABSTRACT
ABSTRACT Background 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. The objective of the study was 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 opaganib/placebo. Results 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. 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 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, hypoxic, hospitalized patients receiving oral opaganib required less supplementary oxygen and had earlier hospital discharge, with no safety concerns arising. These findings support further evaluation of opaganib in this population. Summary Upon receiving opaganib, patients with COVID-19 pneumonia who were hospitalized and required supplemental oxygen showed symptomatic clinical improvement compared to placebo, with less supplemental oxygen requirement, resulting in earlier hospital discharge, and no safety concerns arising.