Supporting Lexicon Pharmaceuticals’ decision to advance the non-opioid analgesic pilavapadin into late-stage development—despite a topline miss in March—is an “improving” regulatory environment for non-addictive options for chronic pain, according to analysts at Jefferies.
Lexicon Pharmaceuticals announced in March that its non-opioid pain medicine pilavapadin will push forward to Phase III testing, despite falling short of significant pain reduction in a mid-stage study. On Wednesday, the Texas-based biotech unveiled follow-up data to support its decision.
A new post-hoc analysis of the Phase IIb PROGRESS trial, which enrolled nearly 500 patients with diabetic peripheral neuopathic pain, showed that a 10-mg daily dose of pilavapadin reached “nominally significant separation from placebo” in terms of pain improvement, according to a news release on Wednesday. Lexicon has identified this dose level as the “most clinically meaningful” dose to take forward. Lexicon presented these data at the 2025 meeting of the European Associated for the Study of Diabetes.
In a topline readout back in March, pilavapadin failed to demonstrate a significant dose-response effect on pain scores compared to placebo—though the biotech at the time blamed it on the highest, 20-mg dose of the analgesic. There was a “lack of separation” between this dose level and placebo in terms of pain outcomes, Lexicon claimed at the time, which led to the overall topline miss. Wednesday’s post-hoc analysis left out the 20-mg arm.
Wednesday’s PROGRESS update also detected a “clinically meaningful” reduction in average daily pain after 11 weeks of treatment.
According to analysts at Jefferies, these findings point to “evidence of an efficacy signal” and are sufficient to support late-stage development for pilavapadin. Further backing the decision to push into Phase III, the firm added, is the “improving” regulatory environment for new treatment options for chronic pain.
However, the Jeffries analysts cautioned that whether the drug can replicate pain reduction in Phase III is still “an open question.” Pilavapadin also has not been tested out to 12 weeks, “a study duration that is preferred by the FDA, the analysts added.
The FDA last week released draft guidelines seeking to streamline the development of non-opioid treatments for chronic pain. Among other things, the regulator said it is open to accepting a “single adequate and well-controlled” trial, plus confirmatory evidence, as the basis for a drug application. The agency also encouraged sponsors to look at “potential biomarkers” that could qualify their investigational product for an expedited review program, such as the fast track, priority review or breakthrough designations.
“The FDA is collaborating closely with sponsors who are developing non-addictive alternatives,” Jefferies wrote. The firm anticipates pivotal studies taking off by year-end or early next year, with topline findings in 2027 to 2028. Jefferies models a “$1B+ blockbuster [potential]” for pilavapadin.
