Core Insights - Lexicon Pharmaceuticals presented clinical data from the Phase 2b PROGRESS study for pilavapadin, an AAK1-inhibitor for diabetic peripheral neuropathic pain (DPNP), showing a two-point reduction in average daily pain scores by week 11 [1][3] - Pilavapadin has the potential to be the first non-opioid oral medication approved for DPNP in over two decades, with the company looking forward to Phase 3 trials [2][5] Study Results - The PROGRESS study evaluated once daily doses of pilavapadin (10 mg, 20 mg) in adults with DPNP, identifying 10 mg as the most clinically meaningful dose [2][3] - A post-hoc analysis indicated significant separation from placebo for the 10 mg dose, with a clinically meaningful reduction in pain scores observed [3] - The 10 mg dose was well tolerated, with minimal discontinuations reported [3] Disease Context - DPNP is a common and debilitating complication of diabetes, affecting approximately 30% of type 1 diabetes patients and 50% of type 2 diabetes patients, with around nine million patients in the U.S. suffering from this condition [4] - There is a significant need for new non-opioid treatments for DPNP, as current options are limited [4] About Pilavapadin - Pilavapadin (LX9211) is a selective, investigational small molecule that inhibits AAK1, targeting neuropathic pain without affecting opiate pathways [6] - Preclinical studies have shown its effectiveness in reducing pain behavior while penetrating the central nervous system [6] About the PROGRESS Study - The PROGRESS study began in December 2023, enrolling 496 adult patients with moderate to severe DPNP, and was designed to evaluate the efficacy of pilavapadin against placebo [7][8] Company Overview - Lexicon Pharmaceuticals focuses on pioneering medicines through its Genome5000™ program, identifying therapeutic targets for various diseases, including neuropathic pain [9]

Core Insights - Lexicon Pharmaceuticals announced positive topline results from the PROGRESS Phase 2b study of pilavapadin, an investigational AAK1 inhibitor for diabetic peripheral neuropathic pain (DPNP), achieving meaningful pain reduction compared to placebo and demonstrating good tolerability at the 10 mg dose [1][5][6] Study Results - The PROGRESS study met its objectives, identifying the 10 mg dose as effective for pain reduction and tolerability, advancing it into Phase 3 development [2][5] - In the PROGRESS study, the 10 mg, 20 mg/10 mg, and 20 mg dose arms achieved reductions in average daily pain scores of 1.74, 1.70, and 1.38, respectively, compared to a reduction of 1.31 in the placebo arm [3] - The 10 mg dose arm showed significant separation from placebo in pain reduction, while the 20 mg dose did not reach statistical significance [3] Adverse Events - Adverse events were more frequent in pilavapadin treatment arms but were milder compared to the RELIEF-DPN-1 study, with dizziness and nausea being the most common [4][6] - The 10 mg dose was generally well-tolerated, while the 20 mg dose had a higher incidence of adverse events leading to patient discontinuations [4] Market Potential - The neuropathic pain market represents a multibillion-dollar opportunity, and pilavapadin could become the first oral non-opioid treatment approved for neuropathic pain in 20 years [6][12] - The results from the PROGRESS study have generated significant interest from potential partners, and the company plans to accelerate discussions while preparing for Phase 3 development [6] Study Background - The PROGRESS study enrolled 496 adult patients with moderate to severe DPNP and was designed to evaluate the efficacy of pilavapadin against placebo [9] - The study's primary endpoint was the change in average daily pain score from baseline to Week 8 [9] Future Plans - A full analysis of the PROGRESS study results will be presented at a medical conference and submitted for publication in a peer-reviewed journal [7]