RedHill Biopharma Announces Positive DSMB Review for Phase 2/3 COVID-19 Study of Opaganib

RedHill Biopharma announced the independent Data Safety Monitoring Board (DSMB) for the global Phase 2/3 study of opaganib in patients with severe COVID-19, unanimously recommended to continue the study following a pre-scheduled futility review of unblinded efficacy data from the first 135 patients treated in the study and safety data from the first 175 patients.

"Opaganib is a novel, orally-administered sphingosine kinase-2 (SK2) inhibitor with demonstrated antiviral, anti-inflammatory, and anti-thrombotic activity. The positive and unanimous DSMB recommendation is a significant milestone in the progress of our development program for COVID-19 disease. Taken together with the positive results from the Phase 2 study, this unanimous DSMB recommendation to continue the global Phase 2/3 study suggests we are heading in the right direction from both a safety and efficacy perspective," said Mark L. Levitt, M.D., Ph.D., Medical Director at RedHill. "This is a particularly difficult time in the fight against the pandemic, with viral mutations increasing infection rates and impacting many aspects of society's response to the pandemic. The need for effective therapeutics is clear. Opaganib's mechanism of action targets the human host cell component SK2, which is involved in both viral replication inside the cell and downstream inflammatory/immune responses. This means that opaganib is expected to maintain its activity irrespective of the worrisome mutations in SARS-CoV-2 spike protein. These mutations underscore the potential of SARS-CoV-2 to develop resistance to direct anti-viral mAbs, and to potentially impact vaccine effectiveness. This is an important advantage of opaganib in the face of the growing multitude of viral strains and provides the promise of a much-needed treatment option to help get patients off oxygen and out of hospital."

This positive DSMB futility review, which is suggestive that the global Phase 2/3 study is progressing as expected, adds to positive top-line safety and efficacy data from the U.S. Phase 2 study, in which opaganib demonstrated greater improvement in reducing oxygen requirement by end of treatment on Day 14 across key primary and secondary efficacy outcomes, correlating with clinical improvement as defined by the World Health Organization (WHO) ordinal scale. The Phase 2 data also showed no material safety differences between the opaganib and placebo treatment arms - further adding to the growing safety database for opaganib. Full analysis of the Phase 2 data, including viral and inflammatory biomarker analyses, baseline risk factors and standard-of-care background therapy stratification, is expected in the coming weeks and is planned to be provided for peer review.

In-line with rapidly evolving clinical practice and guidelines for treatment of hospitalized COVID-19 patients, which aim to minimize patient intubation and mechanical ventilation, the primary endpoint of the global Phase 2/3 study is now the proportion of patients reaching room air (no longer requiring oxygen supplementation) by Day 14, previously a key secondary endpoint. Intubation and mechanical ventilation remains as a secondary endpoint. Correspondingly, a blind resizing of the study is planned, to approximately 460 patients. There are approximately 30 study sites in 7 countries with additional sites and countries being added in the coming days and weeks. Top-line data, and potential global emergency use authorization applications are expected in the second quarter of 2021.

Opaganib, a new chemical entity, is a proprietary, first-in-class, orally-administered, sphingosine kinase-2 (SK2) selective inhibitor with demonstrated dual anti-inflammatory and antiviral activity that targets a host cell component of viral replication, potentially minimizing the likelihood of viral resistance. Opaganib has also shown anticancer activity and has the potential to target multiple oncology, viral, inflammatory, and gastrointestinal indications.

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

Preclinical data have demonstrated anti-inflammatory, antiviral and anti-thrombotic activities of opaganib, with the potential to ameliorate inflammatory lung disorders, such as pneumonia, and mitigate pulmonary fibrotic damage. 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. Opaganib also demonstrated reduced blood clot length, weight and total thrombus score in a preclinical model of Acquired Respiratory Distress Syndrome. Additionally, 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 U.S.-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 and an additional Phase 1 study in multiple myeloma.

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.