Tris Pharma Reports Positive Phase 3 Results for Cebranopadol in Acute Pain
Tris Pharma, Inc. (Tris), a commercial-stage biopharmaceutical company dedicated to developing innovative pain management therapies, has announced positive topline results from its ALLEVIATE-2 Phase 3 pivotal clinical trial evaluating cebranopadol, an investigational therapy designed for the treatment of moderate-to-severe acute pain. This study focused on patients undergoing bunionectomy surgery, while additional promising data from the ALLEVIATE-1 Phase 3 pivotal trial, which evaluated cebranopadol in patients following abdominoplasty surgery, was also detailed.
A New Era in Acute Pain Management
Cebranopadol is a first-in-class pain therapy that works through a novel dual mechanism of action, targeting both the nociceptin/orphanin FQ peptide (NOP) receptor and the µ-opioid peptide (MOP) receptor. This dual-NMR (NOP/MOP receptor) agonism presents a new approach to pain management by leveraging the body’s natural pain modulation processes. Unlike traditional opioids, cebranopadol has the potential to provide significant pain relief while minimizing the risks of dependence, addiction, and other severe side effects associated with opioid use.
The completion of Tris Pharma’s Phase 3 program marks a significant milestone in the development of cebranopadol as a next-generation analgesic. With robust data from both ALLEVIATE-1 and ALLEVIATE-2 trials, the company is now poised to submit a comprehensive data package to the U.S. Food and Drug Administration (FDA) for regulatory review and potential approval.
“With our Phase 3 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,” said Ketan Mehta, CEO and founder of Tris. “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.”
ALLEVIATE-2 Phase 3 Results: Demonstrating Efficacy in Post-Surgical Pain Relief
The ALLEVIATE-2 clinical trial was designed to assess the effectiveness and safety of cebranopadol in managing pain following bunionectomy surgery. The study met its primary endpoint, demonstrating a statistically significant reduction in pain intensity compared to placebo. Pain levels were measured using the Pain Numeric Rating Scale (NRS) Area Under the Curve for two to 48 hours (AUC2-48) following dosing.
Results showed that patients receiving oral cebranopadol 400 µg once daily experienced significant pain relief, with a mean pain reduction that exceeded the pain relief provided by oxycodone immediate-release (IR) 10 mg, which was administered four times per day in a separate study arm. These findings suggest that cebranopadol may offer a comparable or superior level of analgesia while potentially reducing the need for frequent opioid dosing.
Additionally, cebranopadol demonstrated a favorable safety profile, with no serious adverse events reported. The most commonly observed side effect was nausea, which was consistent with other analgesic therapies.
Reduction in Rescue Medication Use
A key secondary endpoint in the ALLEVIATE-2 trial was the need for additional rescue medication. Patients were allowed to use ibuprofen as a first-line rescue medication, with oxycodone IR 5 mg available as a second-line option.
Data revealed that 57.5% of patients receiving cebranopadol did not require opioid rescue medication, compared to only 28.4% in the placebo group. Additionally, cebranopadol-treated patients required significantly fewer doses of rescue medication overall, further supporting its potential role as a safer and more effective pain management solution.
“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,” said Todd Bertoch, M.D., chief medical officer for pain research at CenExel and lead investigator for the ALLEVIATE-2 study. “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 the 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.”
ALLEVIATE-1 Phase 3 Results: Confirming Cebranopadol’s Efficacy in Abdominoplasty Patients
In addition to the ALLEVIATE-2 study, Tris Pharma also provided new insights into the ALLEVIATE-1 Phase 3 pivotal trial, which evaluated cebranopadol’s efficacy in patients experiencing pain following abdominoplasty surgery. Previously announced topline data from this trial indicated that cebranopadol-treated patients experienced significantly greater pain relief compared to those receiving a placebo.
Further analysis of ALLEVIATE-1 data confirmed that cebranopadol-treated patients also required fewer doses of rescue medication than those in the placebo group. This finding aligns with the results from ALLEVIATE-2 and further supports cebranopadol’s potential as a highly effective pain management therapy with reduced opioid exposure.
The Need for a Safer Alternative to Traditional Opioids
The opioid crisis remains a major public health concern, with millions of people affected by opioid misuse, dependence, and overdose. While opioids have long been the gold standard for treating moderate-to-severe acute pain, their high potential for addiction and adverse effects has fueled the search for safer alternatives.
Cebranopadol’s unique dual-NMR mechanism may offer a breakthrough solution to this challenge. By engaging both the NOP and MOP receptors, cebranopadol provides effective analgesia while mitigating some of the negative aspects associated with traditional opioid therapy. This innovative approach could revolutionize pain management by delivering powerful pain relief with a reduced risk of misuse and dependence.
“We are in desperate need of effective medications that provide opioid-level analgesia while minimizing the risk of misuse and abuse,” said Jeff Gudin, M.D., anesthesiologist at the University of Miami, Miller School of Medicine. “Both the ALLEVIATE-1 and -2 trials, as well as promising results from the previous human abuse potential studies, demonstrate cebranopadol’s potential to fill this unmet need for patients suffering from moderate-to-severe acute pain.”
Next Steps: FDA Submission and Potential Market Entry
With the completion of the ALLEVIATE-1 and ALLEVIATE-2 trials, Tris Pharma is now preparing to submit a comprehensive regulatory filing to the FDA. The company plans to present the full results from both Phase 3 trials at an upcoming medical congress .
If approved, cebranopadol could become a groundbreaking new option for pain management, providing patients with a safer, highly effective alternative to traditional opioids. This would mark a major step forward in the field of pain medicine, offering hope to millions of patients who require effective pain relief without the risks associated with opioid therapy.
