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.”
