Effect of Opaganib on Supplemental Oxygen and Mortality in Patients with Severe SARS-CoV-2 Based upon FIO2 Requirements
Authors: Neuenschwander Fernando Carvalho , Barnett-Griness Ofra , Piconi Stefania , Maor Yasmin , Sprinz Eduardo , Assy Nimer , Khmelnitskiy Oleg , Lomakin Nikita V. , Goloshchekin Boris Mikhailovich , Nahorecka Ewelina , Joaquim Westheimer Calvacante Adilson , Ivanova Anastasia , Vladimirovich Zhuravel Sergey , Yurevna Trufanova Galina , Bonora Stefano , Saffoury Amer , Mayo Ami , Shvarts Yury G. , Rizzardini Giuliano , Sobroza de Mello Rogerio , Pilau Janaina , Klinov Alexey , Valente-Acosta Benjamin , Olegovich Burlaka Oleg , Bakhtina Natalia , Bar-Meir Maskit , Nikolaevich Shishimorov Ivan , Oñate-Gutierrez Jose , García Rincón Cristian Iván , Ivanovna Martynenko Tatiana , Hajjar Ludhmila Abrahão , Carolina Nazare de Mendonca Procopio Ana , Simon Krzysztof , Gabriel Chaves Santiago Walter , Fronczak Adam , Roberto Hoffmann Filho Conrado , Hussein Osama , Aleksandrovich Martynov Vladimir , Chichino Guido , Blewaska Piotr , Wroblewski Jacek , Saul Irizar Santana Sergio , Felipe Ocampo Agudelo Andres , Barczyk Adam , lask Gerlach Rachael , Campbell Eppie , Bibliowicz Aida , Fathi Reza , Anderson Patricia , Raday Gilead , Klein Michal , Fehrmann Clara , Eagle Gina , Ben-Yair Vered Katz , Levitt Mark L. 
Published: August 2024

Once a patient has been diagnosed with severe COVID-19 pneumonia, treatment options have limited effectiveness. Opaganib is an oral treatment under investigation being evaluated for treatment of hospitalized patients with severe COVID-19 pneumonia. A randomized, placebo-controlled, double-blind phase 2/3 trial was conducted in 57 sites worldwide from August 2020 to July 2021. Patients received either opaganib (n = 230; 500 mg twice daily) or matching placebo (n = 233) for 14 days. The 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. Pre-specified primary and secondary outcome analyses did not demonstrate statistically significant benefit (except nominally 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 (≥24 h) by day 14 of opaganib treatment increased (76.9% vs. 63.4%; nominal p-value = 0.033). There was a 62.6% reduction in intubation/mechanical ventilation (6.84% vs. 17.91%; nominal p-value = 0.012) and a clinically meaningful 62% reduction in mortality (5.98% vs. 16.7%; nominal p-value = 0.019) by day 42. No new safety concerns were observed. While the primary analyses were not statistically significant, post-hoc analysis suggests opaganib benefit for patients with severe COVID-19 requiring supplemental oxygen with an FIO2 of ≤60%. Further studies are warranted to prospectively confirm opaganib benefit in this subpopulation.