RedHill Biopharma Announces Positive Recommendation from COVID-19 Study

RedHill Biopharma announced its U.S. Phase 2 study with opaganib (Yeliva®, ABC294640) in patients hospitalized with severe COVID-19 pneumonia, has successfully passed the first scheduled independent Safety Monitoring Committee (SMC) review. The SMC reviewed unblinded safety data from the first 12 patients treated for at least seven days, recommending that the study continue without change. The study is more than 50% enrolled and enrollment is expected to be completed in the coming weeks. The next scheduled SMC review will take place once 24 patients complete at least seven days of treatment.

The Company also announced it has received approval from the Italian Medicines Agency (AIFA) for its Clinical Trial Authorization (CTA) application for the global Phase 2/3 study evaluating opaganib in patients hospitalized with severe COVID-19 pneumonia, for which patient enrollment has already commenced.

“The independent SMC’s recommendation to continue the U.S. Phase 2 COVID-19 study without changes is another important step in advancing opaganib as a potential therapy for patients with severe COVID-19. The SMC recommendation further validates the general safety database that we have from treating patients with opaganib, which now numbers more than 140,” said Gilead Raday, RedHill’s Chief Operating Officer. “In parallel, enrollment of the first patients in our global Phase 2/3 study, together with approval for the study in Italy, are additional encouraging steps in our efforts to provide patients with an urgently needed treatment option. Subject to positive data from the studies, we aim to apply for emergency use authorizations as early as the fourth quarter of this year.”

To date, the global Phase 2/3 study has been approved in the UK, Italy, Russia and Mexico, with review ongoing in additional countries and further expansion planned. The multi-center, randomized, double-blind, parallel-arm, placebo-controlled Phase 2/3 study is set to enroll up to 270 patients with severe COVID-19 pneumonia requiring hospitalization and treatment with supplemental oxygen. Subjects are randomized at a 1:1 ratio to receive either opaganib or placebo, in addition to standard-of-care therapy. The primary endpoint of the study is to evaluate the proportion of patients requiring intubation and mechanical ventilation by Day 14. An unblinded futility interim analysis will be conducted by an independent data safety monitoring board (DSMB) when approximately 100 subjects have been evaluated for the primary endpoint.

The U.S. Phase 2 clinical study with opaganib, which is not powered for statistical significance, is a randomized, double-blind, placebo-controlled study, set to enroll up to 40 patients with severe COVID-19 pneumonia requiring hospitalization and supplemental oxygen.

Opaganib, a new chemical entity, is a proprietary, first-in-class, orally-administered, sphingosine kinase-2 (SK2) selective inhibitor with anticancer, anti-inflammatory, and anti-viral activities, targeting multiple oncology, viral, inflammatory, and gastrointestinal indications. By inhibiting SK2, opaganib impacts multiple cellular pathways which are associated with cancer growth, viral replication, and pathological inflammation.

Opaganib was originally developed by U.S.-based Apogee Biotechnology and completed multiple successful preclinical studies in oncology, inflammation, GI, and radioprotection models, as well as a Phase 1 clinical study in cancer patients with advanced solid tumors.

Opaganib received Orphan Drug designation from the U.S. FDA for the treatment of cholangiocarcinoma and is being evaluated in a Phase 2a study in advanced cholangiocarcinoma and in a Phase 2 study in prostate cancer. Opaganib is also being evaluated for the treatment of coronavirus (COVID-19).

Analysis of treatment outcomes in five patients with severe COVID-19 showed substantial benefit to patients treated with opaganib under compassionate use in both clinical outcomes and inflammatory markers as compared to a retrospective matched case-control group from the same hospital. All patients in the opaganib-treated group were discharged from hospital without requiring mechanical ventilation, whereas 33% of the matched case-control group required mechanical ventilation. Median time to weaning from high-flow nasal cannula was reduced to 10 days in the opaganib-treated group, as compared to 15 days in the matched case-control group.

Preclinical data have demonstrated both anti-inflammatory and anti-viral activities of opaganib, with the potential to reduce lung inflammatory disorders, such as pneumonia, and mitigate pulmonary fibrotic damage. Several prior preclinical studies support the potential role of SK2 in the replication-transcription complex of positive-sense single-stranded RNA viruses, similar to coronavirus, and its inhibition may potentially inhibit viral replication. Preclinical in vivo studies2 have demonstrated that opaganib decreased fatality rates from influenza virus infection and ameliorated Pseudomonas aeruginosa-induced lung injury by reducing the levels of IL-6 and TNF-alpha in bronchoalveolar lavage fluids.

The development of opaganib has been supported by grants and contracts from U.S. federal and state government agencies awarded to Apogee Biotechnology Corp., including from the NCI, BARDA, the U.S. Department of Defense and the FDA Office of Orphan Products Development.