Opaganib (ABC294640), a proprietary investigational drug, is a first-in-class, orally administered, small molecule sphingosine kinase-2 (SPHK2)
selective inhibitor with anti-inflammatory, antiviral and anticancer activity targeting multiple potential indications, including gastrointestinal acute radiation syndrome (GI-ARS), viral infections such as COVID-19, Ebola virus disease and additional viruses as part of pandemic preparedness, several cancers, and diabetes and obesity-related disorders.
Inflammatory
Conditions and Medical Countermeasures:
Several U.S. Government and academic countermeasures and pandemic preparedness programs have selected opaganib for evaluation as a medical countermeasure (MCM) for multiple potential indications, including GI-ARS, Ebola virus disease (EBOV) and phosgene inhalation injury. RedHill announced positive preliminary results from in vivo studies evaluating opaganib as a treatment for GI-ARS undertaken as part of the U.S. Government’s National Institute of Allergy and Infectious Diseases (NIAID) Radiation and Nuclear Countermeasures Program (RNCP) product pipeline development contract.
Opaganib is also being evaluated for its potential to treat acute respiratory distress syndrome (ARDS) caused by viruses such as COVID-19 and influenza. Data from the global Phase 2/3 study in hospitalized patients with severe COVID-19 pneumonia offer a compelling rationale for further investigation into opaganib’s potential in treating virus-induced ARDS, potentially supporting a Phase 2/3 study in this indication.
Viral Infections:
Opaganib's suggested mechanism of action, which was published in the journal Drug Design,
Development and Therapy, is host-directed and potentially broad-acting and is expected to maintain effect against
emerging viral variants.
Opaganib is thought to work through the inhibition of multiple pathways, the induction of autophagy and
apoptosis, and disruption of viral replication, through simultaneous inhibition of three
sphingolipid-metabolizing enzymes in human cells (SPHK2, DES1 and GCS).
In COVID-19, opaganib completed a 463-patient global Phase 2/3 study in hospitalized patients with severe COVID-19 pneumonia (NCT04467840). Although the primary endpoint was not met in the prespecified analyses of data from all Phase 2/3 study patients, improvements were observed in the median time to viral RNA clearance as well as in mortality and time to recovery compared to the control arm. Additionally, RedHill announced data from a post-hoc analysis focusing on a subset of patients with moderately severe COVID-19 that demonstrated improvements in clinical outcomes including reduced mortality, shorter time to room air and decreased median time to discharge.
RedHill also announced that BARDA selected opaganib for joint development and funding as a MCM to treat exposure to EBOV and has provided initial funding for the collaboration. Prior to that, RedHill reported positive data from a U.S. Army-funded in vivo study investigating the effects of opaganib on EBOV, along with results from an in vitro study investigating the effects of opaganib and RHB-107 combined individually with remdesivir in a U.S. Army-funded and conducted EBOV study.
RedHill announced the initiation of the Phase 2 Study of opaganib in combination with Bayer’s darolutamide in advanced prostate cancer. The study is being financially supported by Bayer (ETR: BAYN) and the Ramsay Hospital Research Foundation and will be led by Professor Lisa Horvath from Chris O’Brien Lifehouse and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP). Prior to that, opaganib completed an investigator-sponsored Phase 2 study evaluating its safety and efficacy in progressive metastatic castration-resistant prostate cancer (mCRPC) treated with androgen-signaling blockers, abiraterone or enzalutamide (NCT04207255).
Opaganib also completed a U.S. Phase 2a study in patients with advanced unresectable cholangiocarcinoma (NCT03377179) and was granted FDA Orphan Drug Designation for this indication.
Opaganib has completed a Phase 1 clinical study in cancer patients with advanced solid tumors and an investigator-sponsored Phase 1b clinical study in the treatment of multiple myeloma undertaken at Duke University Medical Center.
RedHill also announced that opaganib was granted FDA Orphan Drug Designation for neuroblastoma.
Metabolic Disorders:
RedHill announced positive results from multiple in vivo studies evaluating opaganib on weight gain and glucose tolerance in a high fat diet (HFD) model, providing support for further investigation of opaganib for the prevention and therapy of Type 2 diabetes and other obesity-related disorders.
The
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.
Virtual
Patent Marking
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Yeliva® is a proposed tradename for the drug product containing opaganib, which is
subject to review by the FDA at the time of NDA filing