Microorganisms (Aug 2024)

Effect of Opaganib on Supplemental Oxygen and Mortality in Patients with Severe SARS-CoV-2 Based upon FIO<sub>2</sub> Requirements

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

DOI
https://doi.org/10.3390/microorganisms12091767
Journal volume & issue
Vol. 12, no. 9
p. 1767

Abstract

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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.

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