RedHill Biopharma Receives Approval for COVID-19 Phase 2/3 Study

RedHill Biopharma Ltd. recently announced that 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.

Mark L. Levitt, MD, PhD, Medical Director at RedHill, said “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 US centers.”

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 US (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 that are associated with cancer growth, viral replication, and pathological inflammation.

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 studies 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 US-based Apogee Biotechnology Corp. 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 US 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).

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

RedHill Biopharma Ltd. is a specialty biopharmaceutical company primarily focused on gastrointestinal diseases. RedHill promotes the gastrointestinal drugs Movantik for opioid-induced constipation in adults, Talicia for the treatment of Helicobacter pylori (H. pylori) infection in adults and Aemcolo for the treatment of travelers’ diarrhea in adults. RedHill’s key clinical late-stage development programs include: (i) RHB-204, with a planned pivotal Phase 3 study for pulmonary nontuberculous mycobacteria (NTM) infections; (ii) Opaganib (Yeliva), a first–in–class SK2 selective inhibitor targeting multiple indications with a Phase 2/3 program for COVID-19 and ongoing Phase 2 studies for prostate cancer and cholangiocarcinoma; (iii) RHB-104, with positive results from a first Phase 3 study for Crohn’s disease; (iv) RHB-102 (Bekinda), with positive results from a Phase 3 study for acute gastroenteritis and gastritis and positive results from a Phase 2 study for IBS-D; (v) RHB-106, an encapsulated bowel preparation, and (vi) RHB-107, a Phase 2-stage first-in-class, serine protease inhibitor, targeting cancer and inflammatory gastrointestinal diseases. For more information, visit www.redhillbio.com.