RedHill’s Phase II/III COVID-19 research underway
RedHill Biopharma has received approval from the Brazilian Health Regulatory Agency (ANVISA) for its ongoing global Phase II/III study evaluating opaganib in patients hospitalized with severe COVID-19 pneumonia. The first-in-class, orally administered, sphingosine kinase-2 (SK2) selective inhibitor reportedly has demonstrated dual anti-inflammatory and antiviral activity targeting a host cell component, unaffected by viral mutation, and minimizing the likelihood of resistance.
The ongoing global multi-center, randomized, double-blind, parallel-arm, placebo-controlled study is continuing to enroll patients, with a target of up to 270 patients requiring hospitalization and treatment with supplemental oxygen. To date, the study has been approved in Brazil, Israel, the UK, Italy, Russia and Mexico, with plans to expand further ongoing.
Outsourcing-Pharma (OSP) recently discussed with RedHill Biopharma chief operating officer Gilead Raday (GR) the company’s ongoing research into opaganib, and what lies ahead in their COVID-19 work.
OSP: Could you please provide an overview of RedHill—who you are, key capabilities and specialties, who your clients are and what sets you apart?
GR: RedHill Biopharma is a rapidly growing specialty biopharmaceutical company with a growing range of marketed products and a promising R&D pipeline of new drug candidates, primarily focused on the treatment of gastrointestinal and infectious diseases. The company, which is focused on the US, has a demonstrated track record in drug development and approval and has successfully transformed itself into a leading emerging specialty pharma player; building out its product line-up, advancing a deep and focused pipeline of late-stage clinical assets, including a global Phase II/III program for COVID-19, and establishing an experienced and talented US commercial team to successfully launch and commercialize its range of approved products.
OSP: Please tell us a bit about the history of opaganib and how it came to be pinpointed as a therapy with potential to treat severe COVID-19 patients.
GR: RedHill is developing ogapanib (Yeliva, ABC294640), a first-in-class, orally-administered, SK2 selective inhibitor with demonstrated anti-inflammatory, anti-cancer and antiviral activity. Opaganib is currently being evaluated in a US Phase II and global Phase II/III clinical studies in severe COVID-19.
Its dual anti-inflammatory and anti-viral activity means that opaganib has the potential to greatly benefit COVID-19 patients by inhibiting the key drivers of disease progression - viral replication and lung inflammation. Further, as an orally administered pill with potent anti-viral activity, it could help treat patients across a full range of affected patient populations, from outpatients with mild condition through hospitalized patients with severe symptoms.
As soon as it became clear there were three key elements to severe COVID-19 related disease and symptomology – viral, inflammatory and pulmonary - we knew we had to look more closely at opaganib as a potential novel therapy. Opaganib’s demonstrated anti-viral and anti-inflammatory properties could potentially impact the devastating pulmonary effects of severe COVID-19 infection.
In addition, opaganib targets SK2 which is a human host cell component, rather than targeting a viral component. This means that the target is less likely to be affected by viral mutations, potentially minimizing the risk that the virus develops resistance to the treatment.
Previous clinical and pre-clinical work done with opaganib in oncology indications, including Phase I and Phase II studies, meant we already had safety data from more than 130 patients, and so we were able to move very quickly in devising a developmental path forward for evaluating opaganib in severe COVID-19 patients, the first step of which we announced in April of this year.
We rapidly initiated a compassionate use program for patients with severe COVID-19 who did not have other treatment options. The published data from the treatment of these first patients with opaganib suggested substantial benefit to patients treated with opaganib in both clinical outcomes and inflammatory markers, as compared to a retrospective matched case-control group from the same hospital.
Further supporting the potential of this novel therapy, in a recent preclinical study opaganib completely inhibited SARS-CoV-2 viral replication in in a 3D tissue model of human bronchial epithelial cells which morphologically and functionally resembles the human airway and is similar to the model used to discover SARS-CoV-2. Opaganib compared favorably with remdesivir, the positive control in this study. Previous pre-clinical data had also shown that opaganib reduced mortality rates from influenza virus in in vivo models by reducing the levels of IL-6 and TNF-alpha.
OSP: I understand you’re anticipating the international Phase II/III and parallel US Phase II to kick off in the coming weeks—could you share a more specific target date?
GR: In light of the encouraging data from the compassionate use programs, RedHill initiated two studies in parallel with orally-administered opaganib in severe COVID-19; a global Phase II/III study and a US Phase II study – both are ongoing and advancing rapidly. The U.S. Phase study already 75% enrolled and expected to complete enrollment in the coming weeks.
The phase II/III global study is already approved in UK, Italy, Mexico, Israel, Russia and Brazil, with further expansion ongoing. The US Phase II study is a parallel, randomized, double-blind, placebo-controlled trial in patients with severe COVID-19 (NCT04414618).
Recently, a pre-scheduled independent Safety Monitoring Committee (SMC) recommended that the study continue without change. The study, which is not powered for statistical significance, is set to enroll up to 40 patients requiring hospitalization and supplemental oxygen.
The global Phase II/III study is a multi-center, randomized, double-blind, parallel-arm, placebo-controlled trial (NCT04467840). it was initiated in July 2020 and continues to enroll with a target of up to 270 patients requiring hospitalization and treatment with supplemental oxygen.
The ultimate goal of both of these studies, if positive, is to generate a data set sufficient for successful applications for global emergency use authorizations (EUAs), as quickly as possible.
OSP: Is there anything else you’d like to add?
GR: In addition to opaganib, we are also advancing RHB-107 (Upamostat), a first-in-class, serine protease inhibitor, as a potential treatment option for COVID-19. Host cellular proteases play a critical role in the process of SARS-CoV-2 entry into cells, specifically responsible for activating the SARS-CoV-2 spike (S) protein, which is a prerequisite for the fusion of viral and host cell membranes during viral entry.
RHB-107 also demonstrated potent anti-SARS-CoV-2 activity in a pre-clinical study and we are planning to initiate a US Phase II/III study with RHB-107 in an outpatient setting later this year. We believe we are one of very few companies advancing two COVID-19 treatment options.
In addition, we are excited to advance RHB-204 to a Phase III study in NTM this year, since it has the potential to be the only first-line treatment option available for the debilitating lung condition caused by nontuberculous mycobacteria (NTM) infections.
Stay tuned for the data from our two ongoing COVID-19 trials with opaganib and potential updates on EUAs, if the data are positive.
