Adneuris Files FDA Application for First Dual-NMR Pain Drug Cebranopadol

Adneuris Therapeutics, a wholly owned subsidiary of Tris Pharma, announced Monday it has filed a New Drug Application with the U.S. Food and Drug Administration for cebranopadol to treat moderate-to-severe acute pain in adults. If cleared, the drug would be the first dual NOP/MOP receptor agonist — a dual-NMR — analgesic on the market, bringing a new mechanism to a field that has leaned on the same opioid playbook for decades. The company is based in Monmouth Junction, New Jersey.

The filing rests on two pivotal Phase 3 trials, ALLEVIATE-1 (NCT06545097) and ALLEVIATE-2 (NCT06423703), which tested the drug across two surgical pain models. Cebranopadol at 400 µg met the primary efficacy endpoint in both, cutting pain intensity versus placebo after abdominoplasty (LS mean difference -59.2; p<0.001) and bunionectomy (LS mean difference -56.1; p<0.001). Patients on the drug also reached for significantly less rescue medication than those on placebo (p<0.001), and no drug-related serious adverse events were reported. Nausea, vomiting and dizziness were the most common side effects, each showing up in at least 10% of patients across the studies.

The application carries a broad abuse-potential package built from behavioral pharmacology work, human abuse potential studies and an analysis of abuse- and withdrawal-related adverse events across the program. In recreational opioid users, cebranopadol at doses up to 2.5 times the anticipated maximum therapeutic dose showed significantly lower abuse potential than oxycodone, a Schedule II opioid, and tramadol, a Schedule IV opioid, in head-to-head comparisons. Withdrawal-related adverse events after abrupt discontinuation were rarely reported in studies running up to 14 weeks, and preclinical work suggested the drug was significantly less likely to drive repeated drug-seeking behavior than opioids acting mainly on the mu-opioid receptor.

"Roughly 120 million opioid prescriptions are still written each year in the United States, which shows how much we continue to rely on medications with well-known risks of misuse," said Mark Greenwald, Ph.D., director of the Substance Addiction Research Division at Wayne State University. He called the head-to-head results against oxycodone and tramadol a profile that warrants further attention. Charles Argoff, M.D., of Albany Medical College and past president of the American Academy of Pain Medicine, framed the filing as a milestone for a community that has too often had to pick between real relief and documented risks. Steven P. Cohen, M.D., of Northwestern University Feinberg School of Medicine, noted that undertreated acute pain can turn chronic.

Adneuris chief science and development officer Jim Potenziano credited years of receptor research and thanked trial participants, advocacy groups and physician experts. Cebranopadol has been studied in more than 34 clinical trials involving over 2,400 participants, and Adneuris is also chasing an opioid use disorder indication for it. Next up: the FDA reviews whether the application is complete enough to file, and Adneuris expects word on acceptance within roughly 60 days, at which point the agency would assign a review designation and a PDUFA date.