Tris Pharma’s Cebranopadol Shows Superior Pain Relief and Safety Over Oxycodone at PAINWeek 2024

Tris Pharma, Inc. (Tris), based in Monmouth Junction, New Jersey, has announced compelling data from a clinical study on cebranopadol, an investigational pain therapy. The data reveal that cebranopadol offers robust and extended pain relief with significantly less respiratory depression compared to oxycodone. This investigational drug, a first-in-class dual nociceptin/orphanin FQ peptide (NOP) receptor and µ-opioid peptide (MOP) receptor agonist, is designed to manage various pain types. Key findings will be presented at the PAINWeek 2024 conference in Las Vegas.

James Hackworth, Ph.D., President of the Brand Division at Tris Pharma, expressed satisfaction with the clinical outcomes. He highlighted the importance of these findings, particularly in showcasing the respiratory safety of cebranopadol. Hackworth mentioned the severe impact that opioids have on pain patients and noted that Tris Pharma has collaborated extensively with regulatory bodies to study cebranopadol’s efficacy and safety. Based on encouraging results, cebranopadol has now progressed to two pivotal Phase 3 studies.

The study, "The Effects of Cebranopadol on Ventilatory Drive, Central Nervous System, and Pain," demonstrates how cebranopadol’s NOP receptor activation significantly reduces respiratory depression while providing potent, long-lasting analgesia. The study’s findings indicate that, at doses with equivalent pain relief, cebranopadol causes 25% less respiratory depression compared to oxycodone. Additionally, cebranopadol impacts respiratory parameters more gradually, which allows for a slower accumulation of arterial CO2 and mitigates the full extent of respiratory depression. Notably, cebranopadol maintains prolonged pain relief with a gradual onset and offset, and it results in fewer respiratory adverse events over a 24-hour period compared to oxycodone.

Respiratory depression is a critical and potentially life-threatening side effect of opioid use, often linked to MOP receptor activation. In this double-blind, placebo-controlled study, 30 healthy volunteers were randomized to receive either cebranopadol, oxycodone at supratherapeutic doses, or a placebo over four weeks. The trial used a ventilatory response to hypercapnia model to evaluate the respiratory effects of both drugs and to investigate the potential for a ceiling effect on respiratory depression with cebranopadol at higher doses.

Dr. Simone Jansen from Leiden University Medical Center in the Netherlands, the lead author of the study, pointed out the significance of these findings. According to Jansen, the data suggest that cebranopadol’s novel mechanism of action delays the onset of respiratory effects and reduces the extent of respiratory depression compared to oxycodone. This delayed onset not only extends the timeframe for necessary medical interventions but also contributes to a safer profile for cebranopadol, potentially making physicians more confident in prescribing it if approved.

Cebranopadol (TRN-228) is an investigational drug that acts as a dual-NMR agonist for moderate-to-severe pain and opioid use disorder (OUD). It leverages the properties of the NOP receptor to reduce the risk of misuse and addiction while effectively managing pain. Studied in over 30 clinical trials involving more than two thousand patients, cebranopadol has shown positive results for acute, chronic, and diabetic neuropathic pain with a favorable safety profile. The FDA has granted cebranopadol Fast Track Designation for chronic low back pain, and if approved, it may become the first pain-relief therapy with opioid-equivalent efficacy but significantly lower misuse and addiction risks.

Tris Pharma is a privately-held biopharmaceutical company focused on developing innovative treatments for ADHD, pain, and neurological disorders. The company has an established portfolio of ADHD products and a promising pipeline of near-term drug candidates.