Tris Pharma has announced positive topline results from its ALLEVIATE-1 pivotal Phase 3 clinical trial evaluating cebranopadol, an investigational therapy, for the treatment of moderate-to-severe acute pain in patients following abdominoplasty surgery.

These results add to the growing body of data underscoring the promising efficacy and safety profile of cebranopadol, a first-in-class pain therapy involving dual-nociceptin/orphanin FQ peptide (NOP) receptor and µ-opioid peptide (MOP) receptor (dual-NMR) agonism.

This dual-NMR agonist has the potential to deliver significant pain relief comparable to opioids with minimized risk of significant side effects, dependence and addiction by leveraging the body’s pain biology modulation processes, synergizing the analgesic and safety characteristics of the NOP receptor with the analgesic advantages of the MOP receptor.

The results of the clinical study demonstrated a statistically significant reduction in pain intensity as measured using the Pain Numeric Rating Scale (NRS) Area Under the Curve for the 44 hours following surgery (AUC4-48) as the primary endpoint. Specifically, treatment with cebranopadol 400 µg once per day for two days resulted in a statistically significant reduction in pain intensity compared to placebo (LS Mean difference [SE] of 59.2 [14.36]; p<0.001).

Additionally, cebranopadol was generally well tolerated and exhibited a favorable safety profile that was comparable to placebo, with no serious adverse events related to cebranopadol. The most common adverse event was nausea.

“These are extremely encouraging results, emphasizing the important role cebranopadol could play in effectively and safely alleviating moderate-to-severe acute pain for patients,” said Harold Minkowitz, MD, primary investigator in the ALLEVIATE-1 study and president of analgesics, perioperative & hospital-based research at Evolution Research Group.

“Our team was impressed by the magnitude of analgesia seen, suggesting that cebranopadol’s novel mechanism of dual-NMR agonism has the potential to be as effective as opioids in the post-surgical setting. This analgesic efficacy, combined with evidence from prior clinical studies showing low drug likability and potential for fewer respiratory events, demonstrate that cebranopadol could help address a critical unmet medical need for the millions of people who experience acute pain,” added Minkowitz.

“We are excited by the results from the ALLEVIATE-1 trial demonstrating a strong level of pain relief. The opioid crisis has highlighted the urgent need for pain management options that treat moderate-to-severe pain as effectively as opioids but do not carry similar risk of addiction and detrimental side effects. We believe cebranopadol has the potential to transform the treatment landscape for patients suffering from acute pain,” said Ketan Mehta, Founder and Chief Executive Officer at Tris Pharma.

Tris plans to submit full results from the ALLEVIATE-1 abdominoplasty clinical trial for presentation at an upcoming medical congress. In Q1 2025, Tris also plans to share results evaluating cebranopadol in two additional studies, an intranasal human abuse potential study and ALLEVIATE-2, a Phase 3 clinical study in patients following bunionectomy, with an NDA submission expected later this year. Tris plans to conduct cebranopadol studies in multiple chronic pain indications beginning in the second half of 2025.