Tris Pharma, Inc., a commercial-stage biopharmaceutical company, has announced positive results from the ALLEVIATE-2 Phase 3 pivotal trial for cebranopadol, an investigational first-in-class dual-NMR agonist for moderate-to-severe acute pain. These results, along with data from the ALLEVIATE-1 trial, support Tris Pharma’s plan to submit a New Drug Application (NDA) to the FDA in 2025.
Key Findings from ALLEVIATE-2 Study
- Primary Endpoint Achieved: Cebranopadol demonstrated a statistically significant reduction in pain intensity compared to placebo in patients undergoing bunionectomy surgery.
- Superior to Oxycodone: A post hoc analysis showed cebranopadol had a larger analgesic effect than oxycodone IR (immediate release).
- Reduced Need for Rescue Medication: Fewer cebranopadol-treated patients required additional pain relief compared to placebo in both ALLEVIATE-1 (abdominoplasty) and ALLEVIATE-2.
- Favorable Safety Profile: No serious adverse events were reported, with nausea being the most common side effect.
A Novel Approach to Pain Relief
Cebranopadol is a dual-NMR agonist targeting the nociceptin/orphanin FQ peptide (NOP) receptor and the µ-opioid peptide (MOP) receptor. This dual mechanism:
- Enhances pain relief beyond traditional opioids
- Reduces addiction potential, making it a promising alternative to conventional opioids
- Minimizes side effects associated with standard painkillers
According to Dr. Jeff Gudin, an anesthesiologist at the University of Miami, “We urgently need new medications that provide opioid-level pain relief with a lower risk of misuse. The ALLEVIATE-1 and -2 trials demonstrate cebranopadol’s potential to meet this need.”
Results Summary: ALLEVIATE-2 Trial in Bunionectomy Patients
| Treatment Group | Pain Reduction (AUC2-48) | Comparison to Placebo | P-Value |
|---|---|---|---|
| Cebranopadol 400 µg QD | 223.4 (9.58) | -56.1 (13.49) | < 0.001 |
| Oxycodone IR 10 mg QID | 250.4 (9.53) | -29.1 (13.50) | 0.031 |
| Placebo | 279.5 (9.51) | – | – |
- 57.5% of cebranopadol patients did not require opioid rescue medication, compared to 28.4% of placebo patients (p < 0.001).
- Total doses of rescue medication were lower in cebranopadol-treated patients than in the placebo group (p = 0.004).
Advancing Towards FDA Approval
With both ALLEVIATE trials complete, Tris Pharma plans to submit an NDA to the FDA in 2025. If approved, cebranopadol could redefine acute pain management by offering an effective, safer alternative to opioids.
“Cebranopadol has the potential to revolutionize pain management,” said Ketan Mehta, CEO of Tris Pharma. “Its ability to deliver strong analgesia with lower abuse potential could make it the first-in-class dual-NMR therapy approved for acute pain.”
Next Steps & Future Research
Tris Pharma is preparing to present full results from ALLEVIATE-1 and ALLEVIATE-2 at an upcoming medical conference. Additionally, the company is exploring cebranopadol’s potential for opioid use disorder (OUD) treatment, supported by a $16.6 million NIH grant.
For more information, visit www.trispharma.com.
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