First-In-Class Cebranopadol Moving to Phase 3 Trials

Chronic pain affects millions of individuals daily, often hindering their ability to manage the demands of everyday life. Within the pain management therapeutic landscape, patients usually face a daunting array of options, many of which come with unwanted side effects and limited efficacy. Because therapies frequently fall short, either failing to alleviate pain effectively or resulting in severe side effects and misuse, there is a growing need for new agents that are more effective and safer alternatives.

In a recent press release, Tris Pharma in Monmouth Junction, New Jersey, announced the launch of two phase 3 trials — ALLEVIATE-1 and ALLEVIATE-2 — studying the potential of a first-in-class pain medication with a novel mechanism of action.

As the first dual-NMR agonist, cebranopadol represents a significant advancement in pain therapy.The compoundtargets nociceptin/orphanin FQ peptide (NOP) and µ-opioid peptide (MOP) receptors. The coactivation of these receptors can reduce opioid side effects without compromising pain relief

The two clinical trials will enroll patients recovering from two types of surgical procedures. ALLEVIATE-1 will assess the efficacy of cebranopadol in patients undergoing abdominoplasty, while ALLEVIATE-2 will focus on those undergoing bunion surgery. Together, these studies aim to enroll over 500 patients across multiple U.S. clinical trial sites. The outcomes will contribute to a New Drug Application (NDA) to seek FDA approval for cebranopadol.

Cebranopadol has received Fast Track Designation from the FDA for chronic low back pain.

The ALLEVIATE-1 trial will be a multicenter, randomized, double-blind, placebo-controlled study enrolling up to 300 patients. Its primary goal is to evaluate the analgesic efficacy of cebranopadol compared with placebo in managing pain after full abdominoplasty, as assessed using an 11-point numeric rating scale. Secondary objectives include measuring the use of rescue medication and collecting patient assessments of the study medication.

ALLEVIATE-2 (NCT06423703) will be similar in structure. This trial will enroll up to 240 patients and aim to evaluate the analgesic efficacy of cebranopadol after bunion surgery. It will also compare cebranopadol with oxycodone, evaluating both analgesic efficacy and safety.

According to the press release, Tris Pharma relies on safety and effectiveness data from over 30 clinical trials.The company claims that the data from these studies demonstrate the overall effectiveness of the analgesic effect of cebranopadol and the improved side effect profile.

With the initiation of the ALLEVIATE-1 and ALLEVIATE-2 trials, it remains to be seen how effective cebranopadol is in a larger study population. Should the results from these studies continue to demonstrate an improved safety profile and durable analgesia, this therapy could lead to a new, safer alternative for patients suffering from moderate-to-severe pain.