Opaganib (Yeliva®*, formerly ABC294640), an investigational drug, is a proprietary, oral small molecule sphingosine kinase-2 (SPHK2)
selective inhibitor with potential for broad activity across oncology, infectious diseases and metabolic disorders, with additional evaluation ongoing for opaganib as a radioprotectant. Opaganib has been tested in more than 470 participants in multiple clinical studies and expanded access use.
Infectious Diseases:
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 its 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. RedHill further 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. Such data may offer a compelling rationale for further investigation into opaganib’s potential in treating acute respiratory distress syndrome (ARDS) caused by viruses such as COVID-19 and influenza, which could potentially support a Phase 2/3 study in this indication.
RedHill announced the initiation of patient recruitment into the Phase 2 study evaluating the efficacy of opaganib in combination with Bayer’s darolutamide in men with metastatic castrate-resistant prostate cancer (mCRPC). The study is being financially supported by Bayer 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 mCRPC treated with androgen-signaling blockers, abiraterone or enzalutamide (NCT04207255).
Additional clinical studies completed for opaganib in oncology:
- U.S. Phase 2a study in patients with advanced unresectable cholangiocarcinoma (NCT03377179). Opaganib was also granted FDA Orphan Drug Designation for this indication.
- Phase 1 clinical study in cancer patients with advanced solid tumors.
- Investigator-sponsored Phase 1b clinical study in the treatment of multiple myeloma undertaken at Duke University Medical Center.
Opaganib was also granted FDA Orphan Drug Designation for neuroblastoma.
Metabolic Disorders:
RedHill announced results from multiple in vivo studies, which were published in the journal Diabetes, Metabolic Syndrome and Obesity 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.
Radioprotection:
Opaganib is under evaluation for its potential to protect normal tissue from radiation damage that may occur from exposure to ionizing radiation and remains under investigation for its potential application in the treatment of gastrointestinal radiation exposure (GI-ARS) and as an add-on therapy to cancer radiotherapy. Opaganib has been tested across several mouse models to evaluate its efficacy against radiation-induced tissue damage in collaboration with the U.S. Government (see publication here for additional details). In GI-ARS, development is intended to follow the FDA Animal Rule, and additional experiments are planned in non-human primates to further confirm opaganib’s activity in GI-ARS models.
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.
The Phase 2 study of opaganib in combination with Bayer's darolutamide in advanced prostate cancer is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR; https://www.anzctr.org.au).
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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