RedHill Biopharma Submits COVID-19 Clinical Trial Application for Phase 2/3 Study with Opaganib

The multi-center, randomized, double-blind, parallel-arm, placebo-controlled Phase 2/3 clinical study of opaganib for severe COVID-19 patients is planned to be conducted in Russia and additional European and other countries

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In parallel, a Phase 2a clinical study of opaganib for severe COVID-19 patients is being initiated in the U.S.

TEL-AVIV, Israel and RALEIGH, N.C., June 10, 2020 (GLOBE NEWSWIRE) -- RedHill Biopharma Ltd. (Nasdaq: RDHL) (“RedHill” or the “Company”), a specialty biopharmaceutical company, today announced that it has submitted a Clinical Trial Application (CTA) with the Ministry of Health of the Russian Federation 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 moving rapidly to advance our development program with opaganib for COVID-19. We are expanding the development program to Russia and additional countries, in parallel with the U.S. clinical study, in order to accelerate the collection of robust data on the potential efficacy of opaganib against COVID-19.”

The multi-center, randomized, double-blind, parallel-arm, placebo-controlled Phase 2/3 study is planned to enroll 270 subjects with severe COVID-19 pneumonia requiring hospitalization and treatment with supplemental oxygenation. 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 study is planned to be conducted in clinical sites across Russia and additional European and other countries.

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

Gilead Raday, RedHill’s Chief Operating Officer, added: “We are working closely with government agencies worldwide to allow more patients access to opaganib through clinical studies and compassionate use programs, and are also evaluating governmental funding opportunities for our COVID-19 development programs to address the urgent need for effective therapies.” 

A total of 141 subjects have been dosed with opaganib to date 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.

The Company previously announced encouraging preliminary findings from six COVID-19 patients requiring high-flow supplemental oxygenation 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 oxygenation, 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.

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 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). 

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 adults³, Talicia^® for the treatment of Helicobacter pylori (H. pylori) infection in adults⁴ and Aemcolo^® for the treatment of travelers’ diarrhea in adults⁵. RedHill’s key clinical late-stage development programs include: (i) RHB-104, with positive results from a first Phase 3 study for Crohn's disease; (ii) RHB-204, with a planned pivotal Phase 3 study for pulmonary nontuberculous mycobacteria (NTM) infections; (iii) 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; (iv) Opaganib (Yeliva^®), a first-in-class SK2 selective inhibitor, targeting multiple indications, with an ongoing Phase 1/2a study for cholangiocarcinoma and a development program for COVID-19; (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.