Lexicon Reports Phase 2b Results For Pilavapadin, A Potential First Non-Opioid Oral Therapy For Diabetic Nerve Pain

Author: Benzinga Newsdesk | September 17, 2025 07:11am

Lexicon Pharmaceuticals, Inc. (NASDAQ:LXRX) today announced the presentation of clinical data from the company's Phase 2b PROGRESS study for its investigational, AAK1-inhibitor, pilavapadin, for the treatment of diabetic peripheral neuropathic pain (DPNP) at two medical meetings:

• "New Promise for Painful Diabetic Neuropathy: Results from recently finished clinical trials of Pilavapadin, an oral, non-opioid, AAK1 inhibitor for diabetic peripheral neuropathic pain" was presented on Saturday, September 13, 2025, during an oral presentation at the NEUROdiab Annual Meeting.
• "Pilavapadin, an oral, non-opioid, AAK1 inhibitor for diabetic peripheral neuropathic pain (DPNP): results from a Phase 2b, dose-ranging, randomized, placebo-controlled, multicenter study" was presented on Wednesday, September 17, 2025, during an oral presentation at the 2025 European Association for the Study of Diabetes (EASD) Annual Meeting.

"The data presented at NEUROdiab and EASD provide additional support for our understanding of pilavapadin's profile, as well as its potential as a much-needed new therapy for DPNP," said Suma Gopinathan, Lexicon's Senior Vice President, Discovery. "Pilavapadin has potential to become the first non-opioid, oral medication approved for DPNP in over two decades. We look forward to Phase 3 trials for this potential new therapy."

Study Results

The Phase 2b, dose-finding PROGRESS study evaluated once daily pilavapadin doses of 10 mg, 20 mg, or 20 mg for seven days followed by 10 mg thereafter, in adults with DPNP. Based on results of the study, Lexicon identified pilavapadin 10 mg once daily as the most clinically meaningful dose.

In a post-hoc analysis of the PROGRESS data, excluding the 20 mg arm, the pilavapadin 10 mg dose arms demonstrated nominally significant separation from placebo (p < 0.05). Additionally, a clinically meaningful, two-point reduction from baseline in average daily pain scores (ADPS) was observed by week 11. The pilavapadin 10 mg dose was well tolerated with minimal discontinuations.

"DPNP is a highly prevalent, but often overlooked, debilitating, chronic complication of diabetes in need of new non-opioid treatments," said Rodica Pop-Busui M.D., Ph.D., Jordan Schnitzer Chair in Diabetes, Professor of Medicine and Division Head, Endocrinology, Diabetes and Clinical Nutrition Director, Harold Schnitzer Diabetes Center, Oregon Health & Science University and lead investigator of the PROGRESS study. "AAK1 inhibition represents a promising approach to treating this condition, inducing analgesia by dampening post-neuronal excitability. The Phase 2b PROGRESS study, as well as the prior Phase 2a RELIEF-DPN-1 study, demonstrate that pilavapadin 10 mg was effective in reducing pain scores while maintaining a safety profile in line with current standard of care."

DPNP can result in burning pain, numbness, and other symptoms in the hands, feet, legs, and arms. There are approximately nine million patients in the U.S. who are suffering with DPNP. DPNP affects an estimated 30% of patients with type 1 diabetes and 50% of patients with type 2 diabetes.

Lexicon announced topline results from the PROGRESS trial in March of 2025 and looks forward to presenting additional analyses from its Phase 2 studies at the upcoming Pain Therapeutics Summit October 13-14.

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