Tris Pharma has announced positive topline results from its ALLEVIATE-1 Phase 3 clinical trial, evaluating cebranopadol for the treatment of moderate-to-severe acute pain. The study, which focused on patients following abdominoplasty surgery, demonstrated a statistically significant reduction in pain intensity compared to placebo. These findings suggest that cebranopadol, a first-in-class oral dual-NMR agonist, could offer a new approach to pain management with a minimized risk of side effects, dependence, and addiction.
ALLEVIATE-1 Trial Results
The ALLEVIATE-1 trial (NCT06545097) was a multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the analgesic efficacy of cebranopadol. The primary endpoint was the reduction in pain intensity as measured by the Pain Numeric Rating Scale (NRS) Area Under the Curve for the 44 hours following surgery (AUC4-48).
Results showed that 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). The drug was generally well-tolerated, with a safety profile comparable to placebo. Nausea was the most common adverse event, and no serious adverse events related to cebranopadol were reported.
Expert Commentary
"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, M.D., primary investigator in the ALLEVIATE-1 study and president of analgesics, perioperative & hospital-based research at Evolution Research Group. He added, "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."
Cebranopadol's Novel Mechanism of Action
Cebranopadol (TRN-228) is an investigational therapy that targets both the nociceptin/orphanin FQ peptide (NOP) and μ-opioid peptide (MOP) receptors, acting as a dual-NMR agonist. This mechanism leverages 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. This approach aims to provide effective pain relief while reducing the risk of misuse, dependence, and respiratory depression associated with traditional opioid analgesics.
Future Plans
Tris Pharma plans to submit full results from the ALLEVIATE-1 abdominoplasty clinical trial for presentation at an upcoming medical congress. The company also plans to share results from an intranasal human abuse potential study and ALLEVIATE-2, a Phase 3 clinical study in patients following bunionectomy, in Q1 2025. An NDA submission is expected later this year. Additionally, Tris Pharma intends to conduct cebranopadol studies in multiple chronic pain indications beginning in the second half of 2025.
