Effect of Opaganib on Supplemental Oxygen and Mortality in Patients with Severe SARS-CoV-2 Pneumonia
Authors: Carvalho Neuenschwander Fernando , Barnett-Griness Ofra , Piconi Stefania , Maor Yasmin , Sprinz Eduardo , Assy Nimer , Khmelnitskiy Oleg , Lomakin Nikita , Goloshchekin Boris Mikhailovich , Nahorecka Ewelina , Calvacante Adilson Joaquim Westheimer , Ivanova Anastasia , Zhuravel Sergey Vladimirovich , Trufanova Galina Yurevna , Bonora Stefano , Saffoury Amer , Mayo Ami , Shvarts Yury , Rizzardini Giuliano , Sobroza de Mello Rogerio , Pilau Janaina , Klinov Alexey , Valente-Acosta Benjamin , Burlaka Oleg Olegovich , Bakhtina Natalia , Bar-Meir Maskit , Shishimorov Ivan Nikolaevich , Oñate-Gutierrez Jose , Rincon Cristian Ivan Garcia , Martynenko Tatiana Ivanovna , Abrahão Hajjar Ludhmila , Procopio Ana Carolina Nazare de Mendonca , Simon Krzystof , Santiago Walter Gabriel Chaves , Fronczak Adam , Filho Conrado Roberto Hoffmann , Hussein Osama , Martynov Vladimir Aleksandrovich , Chichino Guido , Blewaska Piotr , Wroblewski Jacek , Santana Sergio Saul Irizar , Agudelo Andres Felipe Ocampo , Barczyk Adam , Gerlach Rachael L. , Campbell Eppie , Bibliowicz Aida , Fathi Reza , Anderson Patricia , Raday Gilead , Klein Michal , Fehrmann Clara , Eagle Gina , Katz Ben-Yair Vered , Levitt Mark L. 
Published: April 2023

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 FiO2levels 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 (≥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.

Trial registration number

NCT04467840