RedHill Biopharma Expands Opaganib COVID-19 Phase 2/3 Study with Clinical Trial Applications in Italy and UK

The multi-center, randomized, double-blind, parallel-arm, placebo-controlled Phase 2/3 clinical study with opaganib in 270 severe COVID-19 patients is planned to be conducted in up to 40 clinical sites across Russia, Italy, the UK and additional countries

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In parallel, a clinical study of opaganib in up to 40 severe COVID-19 patients has been approved by the FDA and is open for recruitment in the U.S.

TEL-AVIV, Israel and RALEIGH, N.C., June 18, 2020 (GLOBE NEWSWIRE) -- RedHill Biopharma Ltd. (Nasdaq: RDHL) (“RedHill” or the “Company”), a specialty biopharmaceutical company, today announced that it has submitted Clinical Trial Applications (CTA) with the UK Medicines & Healthcare Products Regulatory Agency (MHRA) and the Italian Medicines Agency (AIFA) for a Phase 2/3 clinical study evaluating opaganib (Yeliva^®, ABC294640)¹ in patients hospitalized with severe SARS-CoV-2 infection, the cause of COVID-19, and pneumonia.

Mark L. Levitt, M.D., Ph.D., Medical Director at RedHill, said: “We are quickly advancing the preparations for a global, multi-center powered Phase 2/3 study with opaganib for COVID-19. In line with the global shift from a focus on compassionate use programs to adequately controlled clinical studies, our highest priority is on generating robust data in a controlled setting for regulatory purposes. Following our submission of the Clinical Trial Application in Russia last week, we have submitted similar applications in the UK and Italy, and we are looking to expand the study to additional countries and start treating patients soon. This study, along with the ongoing Phase 2a study in the U.S., should allow us to enroll patients faster to evaluate the efficacy of opaganib against COVID-19 and bring this promising therapy one step closer to those who need it.”

The multi-center, randomized, double-blind, parallel-arm, placebo-controlled Phase 2/3 study is planned 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, on top of 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 when approximately 100 subjects have been evaluated for the primary endpoint.

The Company currently plans to conduct the study in up to 40 clinical sites across Russia, Italy, the UK and additional countries.

In parallel, a randomized, double-blind, placebo-controlled Phase 2a clinical study with opaganib in the U.S. is open for recruitment (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. 

The Company previously announced encouraging preliminary findings from six COVID-19 patients requiring high-flow supplemental oxygen treated with opaganib in Israel under compassionate use. All six patients analyzed demonstrated pronounced clinical improvement following treatment initiation with opaganib, substantial improvement in biomarkers, including decreased required supplemental oxygen, higher lymphocyte counts and decreased C-reactive protein (CRP) levels. All six patients analyzed were weaned from supplemental oxygen and discharged from the hospital on room air without having to receive mechanical ventilation.

To date, a total of 141 subjects have been dosed with opaganib in ongoing and completed Phase 1 and Phase 2 clinical studies in oncology indications, in pharmacokinetic studies in healthy volunteers in the U.S., under the existing U.S. Food and Drug Administration (FDA) approved expanded access requests for oncology patients and under the expanded access for COVID-19 patients in Israel, establishing safety and tolerability in humans both in the U.S. and ex-U.S.

About Opaganib (ABC294640, Yeliva^®)
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, inflammatory and gastrointestinal indications. By inhibiting SK2, opaganib blocks the synthesis of sphingosine 1-phosphate (S1P), a lipid-signaling molecule that promotes cancer growth 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-strand single-stranded RNA viruses, similar to SARS-CoV-2, 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 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 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 is also being evaluated for the treatment of SARS-CoV-2 infection (COVID-19). 

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.

About RedHill Biopharma      
RedHill Biopharma Ltd. (Nasdaq: RDHL) is a specialty biopharmaceutical company primarily focused on gastrointestinal diseases. RedHill promotes the gastrointestinal drugs Movantik^® for opioid-induced constipation in adults¹, Talicia^® for the treatment of Helicobacter pylori (H. pylori) infection in adults² and Aemcolo^® for the treatment of travelers’ diarrhea in adults³. 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. More information about the Company is available at www.redhillbio.com.