Cebranopadol, a dual-NMR agonist, reached the primary endpoint in a Phase III trial and matched placebo for safety, a significant concern in the analgesic field.
Tris Pharma reported positive Phase III data Wednesday for its non-opioid painkiller, cebranopadol, showing strong efficacy as well as a solid safety profile.
The New Jersey–based company tested the drug, an agonist of the nociceptin/orphanin FQ peptide (NOP) receptor and µ-opioid peptide (MOP) receptor (known as dual-NMR), in patients who had just undergone abdominoplasty, also known as a tummy tuck. Cebranopadol achieved the primary endpoint in the ALLEVIATE-1 trial, demonstrating a statistically significant drop in pain intensity 44 hours post-operation. Cebranopadol’s safety profile was comparable to placebo, with no adverse events related to the drug, according to a press release.
The results suggest that the drug’s novel mechanism of dual-NMR agonism “has the potential to be as effective as opioids in the post-surgical setting,” Harold Minkowitz, the primary investigator on the trial, said in a statement.
An NDA submission, following another Phase III trial in bunionectomy patients, could be expected later in 2025, according to Tris.
Given the safety and abuse concerns associated with opioids, the biopharma industry is hot on the trail of painkillers that utilize a non-opioid receptor mechanism. Leading the pack is Vertex Pharmaceuticals, which in October unveiled full Phase III data for its sodium-ion channel blocking analgesic suzetrigine. Perhaps spurred on by the success of Vertex and others, Latigo Bio brought in $135 million in a Series A round in February 2024 to advance its own non-opioid-based therapeutics.
Looking forward, observers have predicted further improvements over first-generation non-opioids like Vertex and Tris’s offerings.
Last week at the 2025 J.P. Morgan Healthcare Conference, former Biogen and Sanofi executive Maha Radhakrishnan told BioSpace the field is going beyond sodium-ion channels.
“There’s so many ways to tackle pain, both peripherally and centrally,” said Radhakrishnan, who is currently executive partner at Sofinnova Investments, adding that investigational therapies aim to achieve a shorter time to onset and address drug-drug interactions. “This field needs medications. There’s more to come.”
