Lexicon Completes Enrollment for Phase 2B Study of LX9211 in DPNP

Lexicon Pharmaceuticals, Inc. has announced the successful completion of patient enrollment for its PROGRESS study, which aims to evaluate LX9211, a novel oral small molecule inhibitor of AAK1, for treating diabetic peripheral neuropathic pain (DPNP). The enrollment milestone was achieved ahead of schedule and exceeded the original target by 20%, enrolling 494 patients. This increase in participants is expected to enhance the study's robustness and provide valuable insights for future research.

Craig Granowitz, M.D., Ph.D., Lexicon’s senior vice president and chief medical officer, expressed satisfaction with the enrollment outcome, noting the significant demand for new non-opioid treatments for DPNP. He highlighted that the strong interest in the study resulted in faster than anticipated enrollment, underscoring the urgent need for new therapeutic options for this condition. The company anticipates that the larger participant pool will yield critical insights that will inform the design of Phase 3 trials and strengthen the evidence supporting the use of LX9211 in treating neuropathic pain. Top-line data from the PROGRESS study is expected to be reported in the first quarter of 2025.

The PROGRESS study, which began in December 2023, is a Phase 2b dose-ranging, randomized, double-blind, placebo-controlled, parallel-group, multi-center study with an open-label extension. It targets adult patients with type 1 or type 2 diabetes who suffer from moderate to severe DPNP. The primary endpoint of the study is the reduction in the Average Daily Pain Score (ADPS) at 8 weeks, with secondary endpoints including changes in burning pain and pain interference with sleep.

The study design allows patients to continue on one stable-dose DPNP therapy, such as gabapentin, pregabalin, or duloxetine, without necessitating withdrawal from these therapies even if they are providing partial benefit. This approach aligns with the expected real-world use of new DPNP drugs.

DPNP is a debilitating condition resulting from chronic high blood sugar, leading to nerve damage and causing pain, numbness, and other symptoms in the extremities. Approximately 20 million people in the U.S. experience some form of neuropathic pain, with about 5 million affected by DPNP.

LX9211 was discovered through Lexicon’s innovative gene science approach. It is an investigational drug that has shown promise in preclinical studies by penetrating the central nervous system and reducing pain behavior in models of neuropathic pain without affecting opioid pathways. LX9211 has received Fast Track designation from the U.S. Food and Drug Administration for development in DPNP, reflecting its potential to address a significant unmet medical need.

Lexicon Pharmaceuticals is committed to developing breakthrough medicines that significantly improve patient outcomes. Through its Genome5000™ program, Lexicon has studied nearly 5,000 genes to identify over 100 protein targets with potential therapeutic applications across various diseases. This precision-targeting approach is central to Lexicon’s mission of discovering and developing safe and effective treatments for a range of conditions, including neuropathic pain, hypertrophic cardiomyopathy, obesity, and metabolic disorders.