Tris Pharma's cebranopadol beats placebo on pain in second Phase 3 bunionectomy trial
ALLEVIATE-2 hit its primary pain endpoint and cut opioid rescue use, giving the dual NOP/MOP agonist two positive Phase 3 readouts as Tris Pharma's Adneuris unit prepares an NDA.
Executive Summary
- Cebranopadol met its primary pain-reduction endpoint against placebo in a completed Phase 3 bunionectomy trial, with a favorable safety readout and less need for opioid rescue medication.
- The result is the second pivotal Phase 3 trial in the program to report a positive primary endpoint in acute postsurgical pain, reinforcing the case for a filing rather than establishing it for the first time.
- Tris Pharma is positioning cebranopadol as an alternative to conventional opioids for acute pain, and the sponsor says it plans to submit a New Drug Application built on this and a companion trial.
- No trial in the postoperative pain field shares cebranopadol's dual receptor mechanism, so the readout has no same-mechanism comparator to benchmark against; the closest programs are drugs that manage the same pain model through different targets.
The result
Tris Pharma, Inc., through its newly launched subsidiary Adneuris Therapeutics, disclosed that ALLEVIATE-2 (NCT06423703) met its registered primary endpoint, Pain NRS area under the curve from 2 to 48 hours versus placebo, in a 240-patient completed Phase 3 trial. The press release states cebranopadol "demonstrated a reduction in pain compared with placebo over 48 hours" and reduced use of opioid rescue medication, with a longer time to first rescue dose. The trial enrolled its full target of 240 patients and closed with a favorable safety profile, the company said. NCT06423703+1A Study of Cebranopadol for the Treatment of Acute Pain After BunionectomyNCT06423703Tris Pharma Launches Adneuris Therapeutics to Advance a New Era in Pain MedicineJul 9, 2026
Probability of SuccessBased on the AppliedXL Probability of Success model. For more information about the methodology, read the research here.
The second pivotal trial
ALLEVIATE-2 is the second of two pivotal Phase 3 trials in the program: ALLEVIATE-1 tested cebranopadol after abdominoplasty, and ALLEVIATE-2 tested it after bunionectomy, together enrolling more than 2,400 participants across the broader clinical program. Tris Pharma said both studies showed the same pattern, a reduction in pain versus placebo over 48 hours and reduced opioid rescue use, which the company frames as supporting efficacy comparable to standard-of-care therapies with what it calls a differentiated safety profile relative to oxycodone. Chief Science and Development Officer Jim Potenziano said Adneuris was built "to advance innovative science that has the potential to redefine pain management". TrisTris Pharma Launches Adneuris Therapeutics to Advance a New Era in Pain MedicineJul 9, 2026
Trial design
ALLEVIATE-2 randomized patients across an active comparator arm, an experimental cebranopadol arm, and a placebo arm, with three secondary endpoints: the proportion of subjects requiring opioid rescue medication, a global assessment of satisfaction, and total oxycodone rescue consumption. The trial started on July 18, 2024, and reached its primary completion on January 31, 2025, before moving to Completed status on January 8, 2026. Its primary completion date shifted once, from November 1, 2024 to February 1, 2025, a change made shortly after the trial began recruiting, and the registry shows a single amendment cycle rather than repeated protocol churn. NCT06423703A Study of Cebranopadol for the Treatment of Acute Pain After BunionectomyNCT06423703
Competitive frame
The postoperative pain field carries many small-molecule programs, including local anesthetics such as liposomal bupivacaine and ZYNRELEF, NSAIDs such as ibuprofen and ketorolac, and other opioid-adjacent candidates, but none in the supplied competitive set shares cebranopadol's dual nociceptin/orphanin FQ and mu-opioid receptor mechanism. That leaves cebranopadol without a direct same-mechanism comparator in this indication, so the readout is best read against its own prior trial, ALLEVIATE-1, rather than against a rival asset working through the same biology.
Regulatory path
Tris Pharma said Adneuris "anticipates submitting a New Drug Application (NDA) for cebranopadol," describing it as an investigational dual NOP/MOP receptor agonist for moderate-to-severe acute pain. The company separately disclosed that cebranopadol holds Fast Track Designation for chronic low back pain and that the National Institute on Drug Abuse awarded Tris Pharma a grant to study the drug's potential in opioid use disorder, signaling a broader development plan beyond the acute postsurgical setting. TrisTris Pharma Launches Adneuris Therapeutics to Advance a New Era in Pain MedicineJul 9, 2026
This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.