New Data Shows Cebranopadol’s Potential in Acute Pain Management

Cebranopadol, a first-in-class investigational therapy with the potential to treat multiple types of pain, demonstrated positive results in a recent phase 3 trial evaluating its efficacy and safety in adult patients following bunionectomy surgery.¹ Treatment with cebranopadol resulted in a significant reduction in pain intensity and a higher proportion of patients not requiring opioid rescue medication.

The data from ALLEVIATE-2 (NCT06423703) comes after Tris Pharma released positive data from other clinical trials, including the phase 3 ALLEVIATE-1 (NCT06545097) study and an intranasal human abuse potential study. Those studies showed cebranopadol use resulted in a significant reduction in pain intensity following full abdominoplasty, as well as significantly less likability compared to oxycodone when crushed and taken intranasally. The company said it intends to submit the data from the studies to the FDA as the basis for potential approval.^2,3

In a recent conversation with Drug Topics®, Todd Bertoch, MD, chief medical officer for pain research at CenExel and an investigator on ALLEVIATE-2, discussed the results from the study, how cebranopadol compares to traditional opioids regarding potential for abuse or addiction, the role it could play in the future of pain management, and important things pharmacists should know about it.

“It’s an interesting medication,” Bertoch said. “Some people want to call it an opioid. It does act on the µ-opioid receptor, but it also acts on the [nociceptin/orphanin FQ receptor], which seems to have some counteractive actions as far as opioid addiction and opioid tolerance and things like that. It’s a mixed drug with mixed actions—some people call it a dual action drug but I think it may have even more than 2 different actions. There is evidence that it effects other receptors as well.”

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.businesswire.com/news/home/20250306271136/en/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

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 January 23, 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/

3. Tris Pharma Reports Positive Clinical Results of Intranasal Human Abuse Potential Study Indicating Low Abusability of Cebranopadol, an Investigational, First-in-Class Oral Dual-NMR Agonist for the Treatment of Moderate-to-Severe Pain. News Release. Tris Pharma. January 28, 2025. Accessed January 28, 2025. https://www.businesswire.com/news/home/20250128250701/en/Tris-Pharma-Reports-Positive-Clinical-Results-of-Intranasal-Human-Abuse-Potential-Study-Indicating-Low-Abusability-of-Cebranopadol-an-Investigational-First-in-Class-Oral-Dual-NMR-Agonist-for-the-Treatment-of-Moderate-to-Severe-Pain