Ibuprofen

A New Jersey-based drug company believes it has enough evidence to seek approval for an experimental, first-of-its-kind pain medication.On Thursday, Tris Pharma released data from a clinical trial of about 240 people who had undergone bunion removal, a notoriously painful operation. Results showed that, over a two-day period post surgery, participants given Tris drug experienced a significant reduction in pain intensity compared to those who received a placebo.Tris reported similar findings in January, from a separate trial of people who got tummy tucks. The private company now plans on taking the results from both experiments, plus safety data from several abuse potential studies, and using them to file an approval application with the Food and Drug Administration.Our drug has the potential to become a game-changing opportunity and truly, hopefully, replace the opioid. That's our fundamental goal here, said Ketan Mehta, Tris founder and CEO.Tris drug, known scientifically as cebranopadol, is meant to be a dual-acting painkiller. On one hand, it activates the same brain receptors as opioids the ones which, in essence, muffle the atomic alarm bells that blare when a nerve cell senses pain.Those receptors, though, are also responsible for the euphoric feelings that make opioids so addictive. So to combat this, Tris designed its drug to simultaneously target NOPs, a type of protein researchers suspect not only relieves pain, but helps fine-tune those opioid receptors, effectively checking their safety risks.Tris leaders admit they dont yet know exactly how these molecules interact. But its a problem they, along with members of the broader research community, are working to answer. In the meantime, Mehta and his team point to their data as a sign this is a viable path to treating pain.Were very confident in the data package, said James Hackworth, Tris chief business officer.If cebranopadol does get approved, it would enter a market long dominated by opioids. While there is substantial demand for more options, especially ones without the safety and abuse risks, new pain medications can run into insurance barriers that make getting them to patients difficult.Vertex Pharmaceuticals, one of the worlds largest biotechnology companies, is currently contending with this system. Its medicine Journavx, the first of a new class of non-opioid painkillers, was recently cleared by the FDA as a treatment for the short-lived acute pain typically felt after an accident or surgery. Like Tris drug, the first major tests of Journavx were in people who just had a tummy tuck or bunionectomy and, there, the medicine offered significant relief compared to a placebo.The top concerns surrounding Journavx have so far been price and access, according to Stuart Arbuckle, Vertexs chief operations officer. Doctors, meanwhile, have said that, while excited for this new treatment option, they arent yet sure what pain cases the medicine will be best suited for.Tris has spoken to many experts in the field and, perhaps expectedly, Hackworth claims theyve been impressed by the results generated so far.Both Hackworth and Mehta also note their company was in close consultation with FDA staff while designing the cebranopadol studies. The agency has been very cooperative, and they're as excited for this drug, it seems, as we are, Mehta said. We don't think there would be any hesitation [to approve] on their part.We've gone above and beyond, Hackworth added. On the efficacy side, we've done exactly what they've wanted. And the data is great. On making sure our drug is not abusable, and all these positive safety things, we've done trials beyond what they even require.Even so, some of Tris data could create potential sticking points.In the bunionectomy trial, for example, participants were offered rescue medication either ibuprofen or, in more extreme cases, oxycodone in the week following their surgeries if their pain wasnt adequately controlled. While the proportion of people who needed these medications was significantly higher in the placebo group, it was still around 42% in the cebranopadol arm.Hackworth cautioned that this rate would probably be lower outside the confines of a trial. Thats because the FDA wanted a strict protocol to provide the cleanest look at whether Tris drug was better than a placebo. In the real world, if a patient had still had pain on day four, you would get another dose of cebranopadol, he said. The only thing that was available to them on days 4, 5, 6 and 7 was rescue. So it's not really a real-world situation.The bunionectomy trial also found that roughly 60% of people on Tris drug felt nausea, compared to about 10% of those who got a placebo. The difference is much larger than in the tummy tuck experiment, in which patients were provided an antiemetic and the 20% nausea rate in the drug arm ended up being lower than what was seen with the control. Tris said the nausea cases were mild and easily resolved.Nausea is a common side effect from opioids, and a chief reason why people cant tolerate them for very long. The bunioectomy study had an active comparator arm, wherein participants were instead given oxycodone to manage their pain, and there the nausea rate was about 55%.Notably, Tris said an after-the-fact analysis showed pain intensity scores were numerically lower among participants given its drug versus the oxycodone. The statistical measures used to assess the difference between the two groups indicate that apparent reduction is not conclusive, however.Tris hope is that the Drug Enforcement Administration will not require scheduling for cebranopadol. Cebranopadol leverages an entirely novel mechanism that is differentiated from that of opioids, and the data to-date shows a highly favorable safety and minimal abusable profile, the company said in an emailed statement.Editors Note: This story was updated to include more details from Tristummy tuck trial. '

Tris Pharma has announced positive data from two Phase III trials of cebranopadol, as well as positive data from a human abuse potential (HAP) study to compare the therapy against various opioids. Image credit: Shutterstock / T Schneider. Tris Pharma has reported another Phase III win with its investigational pain therapy, cebranopadol, and it is now setting up a submission for approval to the US Food and Drug Administration (FDA). The US-based biopharma said that the Phase III ALLEVIATE-2 trial (NCT06423703) of its therapy, cebranopadol, met its primary endpoint, demonstrating a statistically significant and high level of pain reduction, measured by the Pain Numeric Rating Scale (NRS), compared to placebo in patients with moderate-to-severe acute pain in patients following bunionectomy surgery. Patients treated with once-daily oral cebranopadol 400µg saw an average reduction in pain of 56.1 points compared to placebo. The need for rescue medicine, analgesic therapies including ibuprofen, to further manage pain in treated patients was also reduced, meeting the trial’s secondary endpoint, with a difference to placebo of 7.8. A separate arm of the study evaluated the therapy against oxycodone immediate release administered orally, four times per day. While oxycodone demonstrated more pain relief compared to placebo, its mean activity was lower than cebranopadol as measured by NRS score. In light of the positive data, the company plans to submit a new drug application (NDA) to the FDA later this year. Tris Pharma CEO Ketan Mehta said: “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.” Earlier this year, Tris posted positive data from the ALLEVIATE-1 study (NCT06545097) , which also met its primary endpoint of analgesic efficacy. The randomised, double-blind, placebo-controlled study evaluated the therapy in patients suffering moderate-to-severe pain following abdominoplasty surgery. Further data from ALLEVIATE-1 saw that cebranopadol-treated patients required significantly fewer doses of rescue medication than patients receiving placebo. The drug was well tolerated and demonstrated a favourable safety profile with no serious adverse events (AEs) observed in both Phase III studies. Cebranopadol is an oral dual nociceptin/orphanin FQ peptide (NOP) receptor and µ-opioid peptide (MOP) receptor agonist. As well as the two Phase III studies, the therapy has been evaluated in a human abuse potential (HAP) study to compare the therapy against various opioids. Many companies are working to develop non-opioid-based pain therapies to address the opioid crisis. Vertex has also had success with its its non-opioid pain therapy VX-548 which met its primary endpoint in two Phase III trials . The company did take a hit, however, when a Phase II trial of the drug did not show a significant improvement over placebo while meeting the primary endpoint. Persica Pharmaceuticals is looking to advance its antibiotic-based combination therapy to registrational studies after it alleviated lower back pain in patients in a Phase Ib study.