Tris cues up filing for non-opioid pain drug on phase 3 win

Tris Pharma has set its sights on an FDA filing for pipeline drug cebranopadol before the end of this year after the drug achieved significant pain relief in abdominoplasty patients in a late-stage trial.

Cebranopadol – a dual-NMR agonist working on nociceptin/orphanin FQ peptide (NOP) and mu-opioid peptide (MOP) receptors – is a potential first-in-class alternative to opioid analgesics, offering similar pain relief with a lower risk of side effects, according to the New Jersey biopharma company.

The new data comes from the phase 3 ALLEVIATE-1 trial, which compared cebranopadol to placebo for the management of moderate-to-severe acute pain following full abdominoplasty – a cosmetic surgery procedure also known as a tummy tuck – in around 300 patients.

Tris' drug outperformed placebo on the main efficacy measure in the study – the pain numerical rate scale (NRS) area under the curve from four through 48 hours (AUC4-48) – which gives a comprehensive view of postoperative pain.

At the higher dose in the trial of 400µg given once daily for two days, cebranopadol achieved a statistically significant reduction in pain intensity compared to the control group, with a safety profile that was "comparable to placebo," according to the company.

The results also showed an average 1.34 mean hourly difference from placebo on the 11-point NRS scale that, according to the investigators of the trial, suggests it could be as effective as opioid drugs.

"This analgesic efficacy, combined with evidence from prior clinical studies showing low drug likability and potential for fewer respiratory events, demonstrates that cebranopadol could help address a critical unmet medical need for the millions of people who experience acute pain," said principal investigator Harold Minkowitz, of Evolution Research Group.

If approved, cebranopadol could be a major step forward in the bid to find effective pain relief free of the side effects and risk of dependency that accompanies the use of opioids and has fuelled an epidemic of overdose deaths in the US and other countries around the world.

The result places Tris amongst a select group of drug developers hoping to bring non-opioid painkillers to market.

The frontrunner at the moment is Vertex Pharma, whose NaV1.8 inhibitor suzetrigine (formerly VX-548) has already been filed for approval in the US for two moderate-to-severe acute pain indications, with an FDA decision due by 30th January after a priority review.

Others working on sodium ion channel drugs for acute pain applications include Latigo Biotherapeutics, which raised $135 million in a Series A last year and has NaV1.8 inhibitors LTG-001 and LTG-305 in phase 1 trials, along with SiteOne Therapeutics, which recently closed a $100 million third-round financing to advance its NaV1.7 and NaV1.8 inhibitors into clinical development.

Later this quarter, Tris is scheduled to report data from a human abuse potential study, as well as the results of ALLEVIATE-2, a companion phase 3 study in patients after bunionectomy surgery. The drug is also being developed for chronic low back pain, chronic neuropathic pain, and substance use disorder.