RedHill Biopharma Ltd. ("RedHill" or the "Company"), a specialty biopharmaceutical company, today announced study results in which opaganib (ABC294640), a leading oral drug candidate for hospitalized patients with moderate to severe COVID-19, was observed to have potent in vitro efficacy against the Omicron SARS-CoV-2 variant, while maintaining host cell viability. Based on the new and previously announced data, opaganib's unique human host-targeted, dual antiviral and anti-inflammatory suggested mechanism is expected to act independently of viral spike protein mutations and remain effective against Omicron sub-variants BA.2, XE and other emerging and future variants.
Work on testing opaganib against Omicron was conducted by the Centre for Immunology and Infection (C2i), The University of Hong Kong's world-renowned infectious diseases research center, School of Public Health, by Dr. Michael Chan, Principal Investigator, of the Centre for Immunology and Infection, who said: "The results of this study showed opaganib exerting potent inhibition of Omicron SARS-CoV-2 variant viral replication in a model that we believe comes as close as currently possible to representing the Omicron clinical pathophysiological pathway. These are highly promising results that lend further weight to opaganib's hypothesized host-mediated antiviral activity and expected effect irrespective of viral variant."
Opaganib was tested for inhibition of Omicron SARS-CoV-2 viral replication using an ex vivo human respiratory explant model, a methodology based on the finding that Omicron has a replication advantage in respiratory tract explants culture. The results of the study, led by Dr. Chan, one of the leading experts in the field whose extensive COVID-19-related research is widely published in top tier journals such as Nature, are encouraging. The results are also consistent with findings from the Phase 2/3 study in which opaganib was shown, together with reducing mortality in key subpopulations and improving the time to recovery, to accelerate viral RNA clearance by more than 4 days, even in an advanced patient population with a median of 11 days from onset of symptoms – we believe a likely first for a novel oral therapy in this underserved hospitalized moderate to severe COVID-19 patient population."
Reza Fathi, PhD., RedHill's Senior VP, R&D
Opaganib was studied in a global Phase 2/3 study in hospitalized patients with severe COVID-19 pneumonia (NCT04467840). In a prespecified analysis of all Phase 2/3 study patients with positive PCR at screening, opaganib improved the median time to viral RNA clearance by at least 4 days, achieving viral RNA clearance in a median of 10 days, while the median for clearance was not reached by the end of 14-days treatment in the placebo arm (Hazard Ratio 1.34; nominal p-value=0.043, N=437/463). Additional prespecified analyses in key subpopulations from the Phase 2/3 study also demonstrated a 70% reduction in mortality and a 34% benefit in time to recovery for patients treated with opaganib.
Regulatory submissions and discussions in the U.S., Europe, UK and additional countries are progressing regarding confirmatory data requirements and pathways to potential approval.
Opaganib, a new chemical entity, is a proprietary, first-in-class, orally-administered, sphingosine kinase-2 (SK2) selective inhibitor, with suggested dual anti-inflammatory and antiviral activity. Opaganib is host-targeted and, based on data accumulated to date, is expected to maintain effect against emerging viral variants, having already shown in vitro inhibition against variants of concern, including Omicron and Delta. Opaganib has also shown anticancer activity and positive preclinical results in renal fibrosis, and has the potential to target multiple oncology, viral, inflammatory, and gastrointestinal indications.
In prespecified analyses of Phase 2/3 clinical data, oral opaganib has demonstrated improved viral RNA clearance, faster time to recovery and significant mortality reduction in key patient subpopulations. Opaganib previously delivered promising U.S. Phase 2 data in patients with moderate to severe COVID-19, submitted for peer review and recently published in medRxiv.
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. Patient accrual, treatment and analysis in this study are ongoing.
Opaganib demonstrated potent antiviral activity against SARS-CoV-2, the virus that causes COVID-19, inhibiting viral replication of the original SARS-CoV-2 and variants tested to date in an in vitro model of human lung bronchial tissue. Additionally, preclinical in vivo studies have demonstrated opaganib's potential to decrease renal fibrosis, have shown decreased fatality rates from influenza virus infection, and amelioration of bacteria-induced pneumonia lung injury with reduced levels of IL-6 and TNF-alpha in bronchoalveolar lavage fluids.
The ongoing clinical 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.
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