TY - JOUR
T1 - Effect of Opaganib on Supplemental Oxygen and Mortality in Patients with Severe SARS-CoV-2 Based upon FIO2 Requirements
AU - Neuenschwander, Fernando Carvalho
AU - Barnett-Griness, Ofra
AU - Piconi, Stefania
AU - Maor, Yasmin
AU - Sprinz, Eduardo
AU - Assy, Nimer
AU - Khmelnitskiy, Oleg
AU - Lomakin, Nikita V.
AU - Goloshchekin, Boris Mikhailovich
AU - Nahorecka, Ewelina
AU - Joaquim Westheimer Calvacante, Adilson
AU - Ivanova, Anastasia
AU - Vladimirovich Zhuravel, Sergey
AU - Yurevna Trufanova, Galina
AU - Bonora, Stefano
AU - Saffoury, Amer
AU - Mayo, Ami
AU - Shvarts, Yury G.
AU - Rizzardini, Giuliano
AU - Sobroza de Mello, Rogerio
AU - Pilau, Janaina
AU - Klinov, Alexey
AU - Valente-Acosta, Benjamin
AU - Olegovich Burlaka, Oleg
AU - Bakhtina, Natalia
AU - Bar-Meir, Maskit
AU - Nikolaevich Shishimorov, Ivan
AU - Oñate-Gutierrez, Jose
AU - Rincón, Cristian Iván García
AU - Ivanovna Martynenko, Tatiana
AU - Hajjar, Ludhmila Abrahão
AU - Carolina Nazare de Mendonca Procopio, Ana
AU - Simon, Krzysztof
AU - Gabriel Chaves Santiago, Walter
AU - Fronczak, Adam
AU - Roberto Hoffmann Filho, Conrado
AU - Hussein, Osama
AU - Aleksandrovich Martynov, Vladimir
AU - Chichino, Guido
AU - Blewaska, Piotr
AU - Wroblewski, Jacek
AU - Saul Irizar Santana, Sergio
AU - Felipe Ocampo Agudelo, Andres
AU - Barczyk, Adam
AU - lask Gerlach, Rachael
AU - Campbell, Eppie
AU - Bibliowicz, Aida
AU - Fathi, Reza
AU - Anderson, Patricia
AU - Raday, Gilead
AU - Klein, Michal
AU - Fehrmann, Clara
AU - Eagle, Gina
AU - Ben-Yair, Vered Katz
AU - Levitt, Mark L.
N1 - Publisher Copyright:
© 2024 by the authors.
PY - 2024/8/26
Y1 - 2024/8/26
N2 - 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.
AB - 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.
KW - ABC294640
KW - COVID-19
KW - SARS-CoV-2 pneumonia
KW - opaganib
KW - sphingosine kinase 2
KW - trial registration number: NCT04467840
UR - http://www.scopus.com/inward/record.url?scp=85205098265&partnerID=8YFLogxK
U2 - 10.3390/microorganisms12091767
DO - 10.3390/microorganisms12091767
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C2 - 39338442
AN - SCOPUS:85205098265
SN - 2076-2607
VL - 12
JO - Microorganisms
JF - Microorganisms
IS - 9
M1 - 1767
ER -