New Cebranopadol Treatment Data Highlight Dual-Receptor Approach to Acute Pain Treatment

Treatment with cebranopadol (Adneuris Therapeutics, Monmouth Junction, NJ), an investigational dual nociceptin/orphanin FQ peptide (NOP) and µ-opioid peptide (MOP) receptor agonist, was associated with reduced pain intensity in 2 phase 3 studies of people with moderate-to-severe acute pain after surgery, according to data presented at PAINWeek 2026.

The phase 3 ALLEVIATE1 (NCT06545097) and ALLEVIATE2 (NCT06423703) clinical trials evaluated cebranopadol treatment in 2 surgical pain models. ALLEVIATE1 included participants who underwent abdominoplasty, and ALLEVIATE2 included participants who underwent bunionectomy. The company also presented abuse-potential data incorporating behavioral pharmacology findings, human abuse-potential studies, and adverse event data related to abuse and withdrawal across the clinical development program.

Cebranopadol is being developed as an investigational analgesic for moderate-to-severe pain. The therapy is designed to activate both NOP and MOP receptors, a mechanism that Adneuris is evaluating as a potential approach to analgesia with a differentiated abuse-potential profile compared with selective MOP receptor agonists.

Phase 3 and Abuse-Potential Findings

• In ALLEVIATE1, participants treated with cebranopadol 400 µg after abdominoplasty showed greater reductions in pain intensity from 4 to 48 hours compared with placebo (least-squares mean difference, -59.2; P<.001).
• In ALLEVIATE2, participants treated with cebranopadol 400 µg after bunionectomy showed greater reductions in pain intensity from 2 to 48 hours compared with placebo (least-squares mean difference, -56.1; P<.001).
• In ALLEVIATE2, treatment with oxycodone was also associated with a statistically significant reduction in pain intensity compared with placebo (least-squares mean difference, -29.1; P=.031).
• Across both phase 3 studies, Adneuris reported lower rescue medication use among participants treated with cebranopadol compared with placebo (P<.001).
• No drug-related serious adverse events were reported with cebranopadol treatment in the phase 3 studies, according to the company.
• In human abuse-potential testing among recreational opioid users, cebranopadol doses up to 2.5 times the anticipated maximum therapeutic dose showed lower abuse-potential measures than hydromorphone, oxycodone, and tramadol, according to Adneuris.
• Euphoria-like adverse events were reported at low rates, and withdrawal-related adverse events after abrupt discontinuation were rarely reported and were not more frequent than placebo in studies lasting up to 14 weeks.
• Preclinical findings suggested lower reinforcement of drug-seeking behavior and weaker physical-dependence signals with cebranopadol than with selective MOP receptor agonists.

Potential Implications for Clinical Practice

For clinicians who manage acute pain or counsel patients about analgesic options, the findings highlight a dual NOP/MOP receptor approach being evaluated for analgesia and abuse-related risk differentiation. The abuse-potential findings may also be clinically relevant if they are confirmed in regulatory review and future peer-reviewed publications, particularly because the data compare cebranopadol with commonly used opioid analgesics.

Source

Adneuris Therapeutics. Adneuris Therapeutics presents novel data on lead candidate, cebranopadol for the treatment of moderate-to-severe acute pain at PAINWeek 2026. Published September 10, 2026. Accessed September 16, 2026. https://www.globenewswire.com/news-release/2026/09/10/3359787/0/en/adneuris-therapeutics-presents-novel-data-on-lead-candidate-cebranopadol-for-the-treatment-of-moderate-to-severe-acute-pain-at-painweek-2026.html