Non-opioid Painkiller(alphamol)

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. '

iStock, Vadim Sazhniev Despite not differentiating itself from placebo, the Texas-based company said it plans to push pilavapadin into Phase III trials before long. In a setback in the race to develop non-opioid painkillers, Lexicon Pharmaceuticals’ candidate has failed to improve pain in a Phase IIb trial. But the company will move the drug on to late-stage tests anyways, citing its “enormous potential.” Lexicon’s shares halved on news the clinical trial failure, falling to about $0.45 per share as the markets opened Monday. Meanwhile, analysts from Jefferies tried to find a silver lining in the data. The firm pointed out that pilavapadin is an add-on to other pain therapies, whereas competitors like Vertex have taken patients off other treatments before administering the investigational option. A key question from the new data will be how many patients were receiving background therapy, the analysts said. The Phase IIb RELIEF-DPN-1 trial tested increasing doses of pilavapadin, a non-addictive adaptor-associated kinase 1 (AAK1) inhibitor in adult patients with diabetes-related pain. In the trial arms of the drug—eight weeks of 10mg, eight weeks of 20mg, or one week of 20mg and then seven weeks of 10mg—patients saw a 1.74, 1.38, and 1.70-point reduction respectively on the mean average daily pain score (ADPS). The placebo arm achieved a 1.31 point reduction, which sunk the trial’s primary endpoint of statistically meaningful “separation” between the drug doses and placebo. The company reported adverse effects like dizziness and nausea, particularly in the 20mg dose arm. Nevertheless, Lexicon plans to push the 10mg dose into a Phase III trial at a later date and the company still hopes to lock in some downstream partnerships for the drug. “The enormous potential of this investigational medicine has generated significant interest from potential partners, and we intend to accelerate these discussions while we plan for Phase III development,” Lexicon CEO Mike Exton said in a statement. Lexicon plans to present more detailed data at an upcoming medical meeting. Pilavapadin met the primary endpoints of a Phase IIa study in 2022, which had a different dosing schedule. Patients took a higher loading dose before dropping down to 10mg or 20mg, which beat placebo. The results announced Monday are another blow for Lexicon, a few months after the FDA rejected its bid for approval of an insulin adjunct sotagliflozin for type I diabetes. The search for non-opioid painkillers has been buoyed by the FDA’s recent historic approval of Vertex’s Journavx, the first new non-opioid painkiller in decades. But even the Big Pharma offering struggled in clinical testing, failing to beat out placebo in a Phase II trial a few months before securing FDA approval. In recent months, companies like Algiax and Tris Pharma have posted positive data for their own non-opioid drugs, while AlgoTx , like Lexicon, stumbled against a “strong placebo effect.”