RedHill Biopharma has announced promising new data showing that its investigational drug opaganib effectively promotes weight loss and improves metabolic markers in preclinical models, potentially positioning the company to compete in the rapidly expanding obesity and diabetes therapeutics market.
The newly published research in the journal Diabetes, Metabolic Syndrome and Obesity demonstrates that opaganib effectively suppresses weight gain and improves glucose tolerance in mice fed a high-fat diet, with efficacy comparable to semaglutide, the active ingredient in Novo Nordisk's blockbuster drugs Ozempic and Wegovy.
Novel Mechanism of Action
Unlike current market leaders such as Novo Nordisk's semaglutide and Eli Lilly's tirzepatide, which are GLP-1 receptor agonists requiring injection, opaganib represents a fundamentally different approach to treating metabolic disorders.
Dr. Mark Levitt, Chief Scientific Officer at RedHill, explained the scientific rationale: "Sphingolipid metabolism is implicated in insulin resistance, β-cell disruption, adipocyte function, inflammation and immune regulation, vascular complications and energy metabolism – all significant components of obesity, diabetes and their associated complications."
The drug works through selective inhibition of sphingosine kinase-2 (SPHK2) and has the unique ability to simultaneously inhibit three sphingolipid-metabolizing enzymes in human cells – making it the first known clinical drug with this mechanism.
Key Findings from Preclinical Research
The preclinical studies revealed several important findings:
- Opaganib markedly suppressed weight gain in mice fed a high-fat diet but not in control diet mice
- Treatment abolished developing glucose intolerance at all measurement timepoints
- The drug reduced hemoglobin A1c elevation and decreased inguinal fat deposition
- Opaganib and semaglutide showed comparable efficacy in promoting weight loss and improving glucose tolerance in obese mice
Perhaps most notably, the research suggests that opaganib may help prevent weight gain rebound after discontinuation of semaglutide treatment – addressing a significant limitation of current GLP-1 therapies.
Potential Market Disruption
The global obesity-diabetes drugs market is projected to reach approximately $100 billion by 2034, driven largely by GLP-1 receptor agonists. As an oral, non-peptide therapeutic, opaganib could potentially address several limitations of current market leaders:
- Oral administration versus injection
- Potentially fewer gastrointestinal side effects
- Novel mechanism targeting multiple metabolic pathways
- Possible prevention of weight rebound after treatment cessation
"As a first-in-class, orally administered, non-peptide option, opaganib could potentially represent a game-changing opportunity in the multi-billion-dollar obesity and diabetes market," noted Dr. Levitt.
De-Risked Development Pathway
RedHill Biopharma has a potential advantage in bringing opaganib to market for metabolic indications due to existing safety and tolerability data from over 470 subjects across several clinical programs. This established safety profile may help expedite the FDA pathway to approval.
Opaganib is already being investigated for multiple other indications, including cancer, inflammatory conditions, and viral diseases. The drug has received orphan drug designations from the FDA in oncology and other diseases, and has undergone studies in solid tumors, advanced cholangiocarcinoma, and prostate cancer.
Broader Development Program
Beyond metabolic disorders, opaganib is being evaluated for several other applications:
- A Bayer-supported Phase 2 study in metastatic castrate-resistant prostate cancer
- U.S. government-supported programs for acute radiation syndrome and viral diseases including Ebola
- Potential applications in COVID-19 based on previous clinical studies
The drug's host-directed mechanism is thought to work through multiple pathways, including the induction of autophagy and apoptosis, and disruption of viral replication, giving it potential broad-spectrum activity.
Company Outlook
For RedHill Biopharma, the positive metabolic data for opaganib represents a strategic expansion of its development pipeline. The company, which already markets the FDA-approved gastrointestinal drug Talicia for Helicobacter pylori infection, has multiple late-stage clinical programs across infectious diseases, gastrointestinal conditions, and oncology.
The addition of obesity and diabetes to opaganib's potential indications significantly increases the drug's market potential and could position RedHill as a competitor in one of the pharmaceutical industry's fastest-growing segments.
As obesity and diabetes continue to represent major global health challenges, innovative approaches like opaganib that offer potential advantages over current therapies will be closely watched by clinicians, patients, and investors alike.
