Compassionate Use of Opaganib For Patients with Severe COVID-19

Abstract

Background. Opaganib is a selective sphingosine-kinase (SK)-2 inhibitor with anti-inflammatory and anti-viral properties. Methods. We provided opaganib on a compassionate-use basis to patients with severe COVID-19. Patients who required oxygen support via high-flow nasal cannula (HFNC) were offered the treatment. For comparison, we used a control group with same-sex, same-severity patients. Results. Seven patients received at least one dose of opaganib since April 2, 2020. One patient, who received both hydroxychloroquine and azithromycin, developed diarrhea and all his medications were stopped. This was the only adverse effect possibly related to opaganib. A second patient was weaned of oxygen and discharged after receiving two doses of opaganib. Therefore, five patients were included in this analysis. Baseline characteristics were not significantly different between cases and controls. Patients treated with opaganib had significantly faster increase in lymphocyte count. All other clinical outcomes had a non-statistically significant trend in favor of the treatment group: median time to weaning from HFNC was 10 and 15 days in cases vs. controls (HR= 0.3, 95% CI: 0.07-1.7, p=0.2) ,time to ambient air was 13 vs.14.5 days (HR=0.4, 95% CI: 0.15-1.5), none of the cases required mechanical ventilation compared with 33% of controls. Conclusion. In this small cohort of severe COVID-19 patients, opaganib was safe and well tolerated with improvement in both clinical and laboratory parameters in all treated patients. The efficacy of opaganib for COVID-19 infection should be further tested in randomized placebo-controlled trials.

COVID-19 therapeutics for low- and middle-income countries: a review of re-purposed candidate agents with potential for near-term use and impact

“…Although no in-vitro evaluation of antiviral activity of opaganib against the SARS CoV2 virus have been published, there has been previous publications demonstrating antiviral effects of targeting the SphK2 enzyme against the Chikungunya virus 81 , Influenza viruses 82 . Based on the postulated anti-inflammatory and antiviral properties, Opaganib was used on the basis of compassionate use in Israel in 7 patients with reported improvement in both clinical and laboratory parameters 83 . Two trials have since then assessed the role of Opaganib.…”

Comparative MD Study of Inhibitory Activity of Opaganib and Adamantane‐Isothiourea Derivatives toward COVID‐19 Main Protease Mpro

“…Some studies show that some anticancer drugs, such as OPG, effects the treatment of COVID-19. [26] In this paper is reported an examination of the inhibitory potency of OPG, 1, 2, 3 and 4 against COVID-19 main protease M pro by the means of molecular docking and molecular dynamic analysis. The structures of studied compounds, optimized at the B3LYP-D3BJ/6-311 + + G(d, p) are given in Table S1.…”

“…It is reported treatment and comparison on the patients' reaction to those of untreated COVID-19 patients with similar disease severity. [26] Recently, the FDA has approved the application for a phase 2, randomized, double-blind, and placebo-controlled study to evaluate OPG effect at patients with moderate-to-severe SARS-CoV-2 pneumonia [NCT04414618]. [26] There are findings that inhibitors such as OPG, Ifenprodil, CM4620-IE, and numerous other treat cytokine storm.…”

“…[26] Recently, the FDA has approved the application for a phase 2, randomized, double-blind, and placebo-controlled study to evaluate OPG effect at patients with moderate-to-severe SARS-CoV-2 pneumonia [NCT04414618]. [26] There are findings that inhibitors such as OPG, Ifenprodil, CM4620-IE, and numerous other treat cytokine storm. [27] In a previous study, a series of adamantane-linked isothiourea derivatives were synthesized, [28] which have been found to exhibit potent broad-spectrum antibacterial activity.…”

Opaganib in COVID-19 pneumonia: Results of a randomized, placebo-controlled Phase 2a trial

“…We hypothesized that the antiviral and anti-inflammatory effects of opaganib would be beneficial for the treatment of SARS-CoV-2 infection, particularly for patients with moderate to severe COVID-19 pneumonia requiring supplemental oxygen. In a small cohort of patients with severe COVID-19 pneumonia, where opaganib was offered through compassionate use, it appeared to improve clinical and laboratory parameters in treated patients, and was safe and well tolerated (17). This Phase 2a proof-of-concept, placebo-controlled study was designed to evaluate the effect of opaganib when added to SoC in hospitalized patients with COVID-19 pneumonia who required supplemental oxygen.…”