Investigational Pain Therapy Cebranopadol Succeeds in Second Phase III Clinical Trial

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Tris Pharma has announced positive, topline results from its ALLEVIATE-2 Phase III clinical trial of cebranopadol, an investigational, first-in-class oral dual-NMR agonist for the treatment of moderate-to-severe acute pain in patients following bunionectomy surgery.¹ These results follow an earlier Phase III win for cebranopadol, which was shared by Tris in January 2025.²

In ALLEVIATE-2, cebranopadol was administered to patients following bunionectomy. It met the primary endpoint by demonstrating a statistically significant reduction in pain intensity as measured using the Pain Numeric Rating Scale (NRS) Area Under the Curve for two to 48 hours after dosing. The secondary endpoint of the trial was also met with a reduction in the use of rescue medications compared to placebo.

In a press release, Todd Bertoch, MD, chief medical officer for pain research at CenExel and lead investigator for the ALLEVIATE-2 study, said, “These are extremely encouraging results that emphasize the important role dual-NMR drugs could play in treating moderate-to-severe acute pain with much lower risk of the misuse, physical dependence, addiction or overdose seen with opioids while still being able to provide a comparable level of analgesia. The biggest challenge in the search for new drugs for pain has been finding something safe that can treat more severe pain that today requires use of an opioid. The level of analgesia seen across both ALLEVIATE-1 and ALLEVIATE-2 as well as the safety data that has been generated suggest that cebranopadol could fulfill this urgent need.”

Ketan Mehta, CEO and founder of Tris added, “With our Phase III program for cebranopadol in the treatment of moderate-to-severe acute pain complete, we now have a comprehensive data package that will be submitted to the FDA as the basis for potential approval. If approved, cebranopadol has the potential to redefine the standard of care for acute pain management, offering a first-in-kind treatment option for patients in need.”

As mentioned earlier, Tris previously shared positive results from its ALLEVIATE-1 Phase III study of cebranopadol in patients following abdominoplasty surgery. Once again, the primary endpoint was achieved with cebranopadol showing a statistically significant reduction in pain intensity.

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

The ALLEVIATE-1 and ALLEVIATE-2 trials plus human abuse potential studies comparing against various opioids constitute the full Phase III program for cebranopadol in the treatment of moderate-to-severe acute pain. Having seen positive results in each of these studies, Tris plans to submit a New Drug Application to the FDA in 2025.

References

1. Tris Pharma Announces Positive Results from ALLEVIATE-2 Phase 3 Pivotal Trial for Cebranopadol, an Investigational First-in-Class Oral Dual-NMR Agonist, for the Treatment of Moderate-to-Severe Acute Pain. News release. Tris Pharma. March 6, 2025. Accessed March 6, 2025. https://www.trispharma.com/tris-pharma-announces-positive-results-from-alleviate-2-phase-3-pivotal-trial-for-cebranopadol-an-investigational-first-in-class-oral-dual-nmr-agonist-for-the-treatment-of-moderate-to-severe-acute-p/

2. Tris Pharma Announces Positive Results from ALLEVIATE-1 Phase 3 Clinical Trial of Cebranopadol, an Investigational First-in-Class Oral Dual-NMR Agonist, for the Treatment of Moderate-to-Severe Acute Pain. News release. Tris Pharma. January 22, 2025. Accessed March 6, 2025. https://www.trispharma.com/tris-pharma-announces-positive-results-from-alleviate-1-phase-3-clinical-trial-of-cebranopadol-an-investigational-first-in-class-oral-dual-nmr-agonist-for-the-treatment-of-moderate-to-severe-acute-p/