RedHill Biopharma announced the UK Medicines & Healthcare products Regulatory Agency (MHRA) has approved the Company’s Clinical Trial Authorization (CTA) application to commence a Phase 2/3 study evaluating opaganib (Yeliva?, ABC294640) in patients hospitalized with severe SARS-CoV-2 infection (the cause of COVID-19) and pneumonia. RedHill has also submitted CTA applications for this study in Russia and Italy and plans to expand the study to additional countries.

“This timely approval from the UK regulatory authority for the Phase 2/3 study with opaganib comes as the global infection rates continue to grow and there remains a serious unmet medical need for a safe and effective treatment for COVID-19. We are rapidly advancing our COVID-19 program with opaganib, including the recently initiated Phase 2a study in leading U.S. centers,” Mark L. Levitt, M.D., Ph.D., Medical Director at RedHill, said.

The multi-center, randomized, double-blind, parallel-arm, placebo-controlled Phase 2/3 study is set to enroll up to 270 subjects with severe COVID-19 pneumonia requiring hospitalization and treatment with supplemental oxygen. Subjects will be randomized at a 1:1 ratio to receive either opaganib or placebo, along with 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 only 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 study is planned to be conducted in clinical sites across Italy, the UK, Russia and additional countries.

In parallel, RedHill has initiated enrollment for a randomized, double-blind, placebo-controlled Phase 2a clinical study with opaganib in the U.S. (NCT04414618). This study is set to enroll up to 40 patients with severe COVID-19 pneumonia requiring hospitalization and supplemental oxygen. This clinical trial is not powered for statistical significance.

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.

Pre-clinical 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 pre-clinical 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. Pre-clinical 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.

Opaganib was originally developed by U.S.-based Apogee Biotechnology Corp. and completed multiple successful pre-clinical 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 1/2a in advanced cholangiocarcinoma and in a Phase 2 study in prostate cancer. Opaganib is also being evaluated for the treatment of coronavirus (COVID-19).