RedHill Biopharma Announces Last Patient Out for Phase 2/3 COVID-19 Study of Oral Opaganib

RedHill Biopharma Ltd. (Nasdaq: RDHL) ("RedHill" or the "Company"), a specialty pharma company that is a leader in the development of novel oral therapies for COVID-19, today announced that all treatment and follow-up has now been completed in the 475-patient global Phase 2/3 study with opaganib (ABC294640)[1] in patients hospitalized with severe COVID-19 pneumonia (NCT04467840). Top-line results are expected in the coming weeks. 

Opaganib is a novel, host-targeted, dual antiviral and anti-inflammatory investigational pill in advanced clinical development for the treatment of severe COVID-19. Opaganib recently demonstrated potent in vitro inhibition of the Beta (South African) and Gamma (Brazilian) variants and based on its unique host-targeted mechanism and the preliminary results from this study, we believe opaganib is likely to also maintain its activity against emerging variants, including Delta and Delta Plus. Positive U.S. Phase 2 efficacy data has also previously been announced. 

"Emerging data is showing that variants are capable of evading vaccines' effects. Not only does this threaten efforts to control the pandemic, but it also brings into sharp focus the urgent need for effective oral COVID-19 therapies capable of working despite the emergence of variants. This makes the completion of this study even more significant, given its potential to be a game-changer in the treatment of COVID-19," said Mark L. Levitt, MD, Ph.D., Medical Director at RedHill. "We can now concentrate on getting all the data collected, cleaned and collated in the database ready for analysis and subsequent reporting. This means we are weeks away from knowing if we are a big step closer to having a paradigm-shifting oral therapy for hospitalized COVID-19 patients."

The primary endpoint of the global Phase 2/3 study, approved in 10 countries, is the proportion of patients breathing room air without oxygen support by Day 14. The study has also captured additional important outcome measures, such as the time to hospital discharge, improvement according to the World Health Organization Ordinal Scale for Clinical Improvement and incidence of intubation and mortality.

Evaluations of blinded blended intubation and mortality rates from the Phase 2/3 study have been encouraging compared to reported rates of mortality from large platform studies such as RECOVERY, and other studies in similar patient populations[2]. Furthermore, four independent DSMB recommendations to continue the study have been received following three unblinded safety reviews and an unblinded futility analysis. Additionally, encouraging use of opaganib under compassionate use exemption has been experienced in Israel and Switzerland.

The Company maintains ongoing discussions with the FDA, EMA and other regulators, on potential pathways to approval, with next steps to be guided by study results. Discussions are also ongoing with potential partners who are interested in the rights to opaganib in various countries.  

About Opaganib (ABC294640[3])

Opaganib, a new chemical entity, is a proprietary, first-in-class, orally-administered, sphingosine kinase-2 (SK2) selective inhibitor, with dual anti-inflammatory and antiviral activity, that is host-targeted and is therefore expected to be effective against emerging viral variants. Opaganib has also shown anticancer activity and has the potential to target multiple oncology, viral, inflammatory, and gastrointestinal indications. 

Opaganib is being evaluated as a treatment for COVID-19 pneumonia in a global Phase 2/3 study that has now completed patient treatment and follow-up. Opaganib has also demonstrated positive safety and efficacy signals in preliminary top-line data from a 40-patient U.S. Phase 2 study. 

Opaganib has also 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 demonstrated potent antiviral activity against SARS-CoV-2, the virus that causes COVID-19, completely inhibiting viral replication in an in vitro model of human lung bronchial tissue. Additionally, preclinical in vivo studies have demonstrated opaganib's potential to ameliorate inflammatory lung disorders, such as pneumonia, and have shown decreased fatality rates from influenza virus infection and amelioration of Pseudomonas aeruginosa-induced lung injury by reducing the levels of IL-6 and TNF-alpha in bronchoalveolar lavage fluids[4]. 

The ongoing studies with opaganib are registered on www.ClinicalTrials.gov, a web-based service by the U.S. National Institute of Health, which provides public access to information on publicly and privately supported clinical studies.   

About RedHill Biopharma     

RedHill Biopharma Ltd. (Nasdaq: RDHL) is a specialty biopharmaceutical company primarily focused on gastrointestinal and infectious diseases. RedHill promotes the gastrointestinal drugs, Movantik® for opioid-induced constipation in adults[5], Talicia® for the treatment of Helicobacter pylori (H. pylori) infection in adults[6], and Aemcolo® for the treatment of travelers' diarrhea in adults[7]. RedHill's key clinical late-stage development programs include: (i) RHB-204, with an ongoing Phase 3 study for pulmonary nontuberculous mycobacteria (NTM) disease; (ii) opaganib (ABC294640), a first-in-class SK2 selective inhibitor targeting multiple indications with positive Phase 2 COVID-19 data and an ongoing Phase 2/3 program for COVID-19 and Phase 2 studies for prostate cancer and cholangiocarcinoma ongoing; (iii) RHB-107 (upamostat), a serine protease inhibitor in a U.S. Phase 2/3 study as treatment for symptomatic COVID-19, and targeting multiple other cancer and inflammatory gastrointestinal diseases; (iv) RHB-104, with positive results from a first Phase 3 study for Crohn's disease; (v) 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; and (vi) RHB-106, an encapsulated bowel preparation.