Adneuris presents Phase 3 and abuse-potential data for cebranopadol

Adneuris Therapeutics, a wholly owned subsidiary of Tris Pharma, has presented new clinical and pharmacological data for its lead candidate cebranopadol at PAINWeek 2026 in Las Vegas, adding to the evidence package the company intends to file in a New Drug Application later this year.

The data set covers two distinct domains: pivotal efficacy results from the Phase 3 ALLEVIATE programme, and a comprehensive assessment of the drug's abuse potential relative to approved opioid comparators.

Phase 3 efficacy results

The ALLEVIATE-1 and ALLEVIATE-2 studies evaluated cebranopadol 400 micrograms in patients undergoing abdominoplasty and bunionectomy, respectively, representing soft- and hard-tissue surgical pain models. Both studies met their primary endpoints. In ALLEVIATE-1, cebranopadol showed a least-squares mean difference in pain intensity of -59.2 versus placebo over the 4-to-48-hour window (p less than 0.001). In ALLEVIATE-2, the equivalent figure was -56.1 over 2 to 48 hours (p less than 0.001), compared with -29.1 for oxycodone in the same study. Rescue medication use was significantly lower with cebranopadol than with placebo across both trials, and the company reported no drug-related serious adverse events.

Cebranopadol is a first-in-class dual nociceptin/orphanin FQ peptide (NOP) and mu-opioid peptide (MOP) receptor agonist. Adneuris and its parent Tris Pharma argue that stimulating the NOP receptor alongside the MOP receptor tempers the abuse-related and dependence-generating signals typically associated with selective MOP agonists such as oxycodone.

Abuse potential assessment

The abuse potential data presented at PAINWeek drew on behavioural pharmacology studies, human abuse potential studies in recreational opioid users, and adverse event analyses from the broader clinical programme of more than 2,400 subjects. At doses up to 2.5 times the anticipated maximum therapeutic dose, cebranopadol showed lower abuse potential than the Schedule II opioids hydromorphone and oxycodone, and the Schedule IV opioid tramadol. Euphoria-like events were infrequent, and withdrawal-related adverse events following abrupt discontinuation were no more common than placebo in studies of up to 14 weeks.

James Hackworth, PhD, cebranopadol development lead at Adneuris, said the dual NOP/MOP mechanism "is designed to provide meaningful pain relief while potentially mitigating many of the risks associated with existing treatments," adding that the data support a "better benefit-risk profile" for patients and physicians managing moderate-to-severe acute pain.

Regulatory and competitive context

The FDA has granted cebranopadol Fast Track Designation for chronic low back pain, and the company has flagged an NDA submission for the acute pain indication later in 2026. A successful filing would put cebranopadol before the agency at a time when regulators and policymakers remain acutely sensitive to the risks of new opioid-class analgesics; any scheduling decision by the Drug Enforcement Administration will be as consequential to the drug's commercial trajectory as the FDA approval itself.

The non-traditional opioid space has seen sustained interest from both industry and public funders. The National Institute on Drug Abuse has awarded Tris Pharma a five-year grant of up to 16.6 million dollars to study cebranopadol's potential in opioid and substance use disorders, a secondary development path that could broaden the drug's value proposition considerably if the acute pain NDA advances.

Competitors pursuing differentiated analgesic mechanisms include companies working on Nav1.7 channel blockers, kappa-opioid agonists, and non-opioid central sensitisation approaches, none of which has yet reached late-stage approval in acute pain. If the abuse potential profile holds through regulatory scrutiny, cebranopadol's dual-receptor rationale may prove a more straightforward regulatory argument than entirely novel mechanisms, given that the MOP pharmacology is already well characterised by the agency.