REDHILL BIOPHARMA
IMAGE: REDHILL’S OPAGANIB MECHANISM UNAFFECTED BY OMICRON MUTATIONS
CREDIT: REDHILL BIOPHARMA
TEL AVIV, Israel and RALEIGH, NC, December 6, 2021, RedHill Biopharma Ltd.(Nasdaq: RDHL) (“RedHill” or the “Company”), a specialty biopharmaceutical company, today announced that because opaganib’s proposed mechanism of action is not impacted by spike protein mutations, opaganib is expected to be unaffected by mutations associated with Omicron and other known variants of concern. The Company also provided an update on the status of its regulatory submissions for opaganib.
Increased hospitalizations in South Africa due to Omicron highlight the urgent need for drugs aimed at moderately severe COVID-19 patients with pneumonia requiring hospital treatment. By focusing on this large group of patients, opaganib, if approved, would target an entirely different and sicker patient population than the Pfizer and Merck oral drug candidates, which showed benefit only in non-hospitalized patients at the earliest stages of symptomatic infection.
Opaganib acts independently of mutations to the viral spike protein. We believe that its unique proposed mechanism of action – targeting a protein in the human cell required by the virus for replication rather than the virus itself – holds significant potential versus Omicron and other existing and emerging variants with mutations to the spike protein. Extensive clinical and non-clinical data support the rationale for accelerating this program, including clinical data from Phase 2 and Phase 2/3 studies, compassionate use experience, and strong inhibition against variants of concern, including Delta.
“Omicron is just another reminder that COVID-19 is an endemic virus at this point, and it is not going away. The evolution of this virus will continue as long as it circulates, and we will need to continue to tweak our vaccines and monoclonal antibodies in order to respond to new variants as they arise. Most importantly, this underscores the need for safe and effective anti-viral therapies that will continue to work no matter which variants present themselves. It is vital that focus, time, and resources are given to the development of anti-viral therapies that can effectively treat those COVID-19 high risk patients, preferably without concern for variants and mutations,” said Kevin Winthrop, MD, MPH, Professor of Infectious Diseases at Oregon Health & Science University. “The post-hoc data from the opaganib Phase 2/3 study in moderate and severe COVID-19 patients is intriguing and suggests the possibility that opaganib might prove itself as an effective anti-viral in this setting. In a subpopulation of patients defined as moderately severe based on their level of baseline oxygen supplementation, mortality was 62% lower in those using opaganib (16% placebo Vs. 6% opaganib). The results suggest a sub-group of patients who would likely benefit from this therapy, and they highlight the need for additional studies in the development of this therapy.”
Regulatory & Development Update:
Given the promising clinical results to-date in the moderately severe hospitalized patient population in a large subpopulation analysis of the global Phase 2/3 study, RedHill is vigorously pursuing the development program for opaganib:
- Submitted data packages to the U.S. FDA, the European Medicines Agency (EMA), and the UK (MHRA) actively seeking scientific advice on the potential path towards approval of opaganib. The EMA has indicated a rapid procedure timeline, and we expect their advice by end of the year, with preliminary feedback from the FDA expected in January 2022.
- Pursuing submission in other countries including South Africa, Russia, Israel, Switzerland, India, Brazil, and Colombia.
- Discussions and preparation ongoing for a confirmatory study with opaganib in the targeted moderately severe hospitalized patient group, engaging with the FDA, other regulatory bodies as well as other government agencies on the need to further accelerate development of much needed therapeutics, such as opaganib and RHB-107, against Omicron and emerging variants.
- A number of pending grant applications in the U.S. and abroad with both government bodies and non-government entities.
“Both opaganib and RHB-107 have unique human cell-targeted mechanisms of action that act independently of mutations at the spike protein. Given the gravity of the threat presented by Omicron, and the likely emergence of other variants, RedHill is pursuing development of these two promising COVID-19 pills as quickly and diligently as possible. We have extensive safety data and, in the case of opaganib, an apparent clinical benefit in reducing mortality, getting patients back onto room air and getting them out of hospital faster,” said Gilead Raday, RedHill’s Head of R&D “Importantly, opaganib benefited a population of hospitalized patients in moderately severe condition with treatment being initiated a median of 11 days from the onset of symptoms in our Phase 2/3 global study. This distinguishes opaganib as a potential game-changer for advanced COVID-19 patients who are at a significant risk of dying from their condition and already well beyond the 3-5-day from symptom onset scope offered by the Pfizer and Merck anti-viral pills.”
Unique Opaganib Proposed Mechanism of Action:
Opaganib is a sphingosine kinase-2 (SK2) inhibitor, a promising and differentiated approach that targets the SK2 human host cell factor rather than the virus itself, working independently of spike protein mutations, such as those associated with Omicron and emerging variants of concern. SARS-CoV-2, the virus which causes COVID-19 disease, is a positive-sense single-stranded RNA (+ssRNA) virus, which account for more than one-third of all known virus genera. These viruses use host factors in various steps of viral infection, such as cell entry and replication – SK2 is one such factor, potentially making it a broad-spectrum antiviral target. SK2 is also active in the modulation of certain pro-inflammatory cytokines, with in vivo studies demonstrating opaganib’s potential to ameliorate inflammatory lung disorders and decrease renal fibrosis by reduction of IL-6 and TNF-alpha levels in bronchoalveolar lavage fluids. Thus, inhibition of SK2 may deliver a 2-pronged antiviral and anti-inflammatory effect – a highly desirable mechanism in the case of COVID-19. Moreover, opaganib’s targeting of SK2 and not the virus itself, means it is expected to uphold antiviral activity irrespective of the worrisome mutations in the SARS-CoV-2 spike protein and the emergence of new strains, such as Omicron, which may be evasive of direct antiviral antibodies and vaccines.
RHB-107 Mode of Action and Development Status
RHB-107], RedHill’s other oral COVID-19 drug candidate, is a once-daily oral capsule, given early in the course of the disease, to outpatients. It targets Serine Proteases, which are human enzymes that are involved in facilitating the entry of SARS-CoV-2 into target cells. The cleaving of the spike protein by these host human serine proteases, is a necessary step in viral attachment and entry into the cells, which is independent of the mutations observed in the Omicron variant that are altering the spike-protein antigenic properties.
RHB-107 is currently being evaluated in a Phase 2/3 study in non-hospitalized COVID-19 patients in the U.S. and in South Africa. Recruitment for part A of the study has been completed and top-line results are expected in the first quarter of 2022.
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