Lexicon Phase 2b pain trial misses statistical significance on primary endpoint

 In the PROGRESS study, all pilavapadin treatment arms demonstrated reductions in the mean average daily pain score (ADPS) from baseline to Week 8 with the 10 mg, 20 mg/10 mg and 20 mg dose arms achieving reductions of 1.74, 1.70 and 1.38, respectively, compared to a reduction of 1.31 in the placebo arm. The study’s statistical analysis plan was designed to detect a dose-response signal based on a prespecified model that assumed separation of all treatment arms from placebo when measuring the primary endpoint of change from baseline to Week 8 on ADPS as compared to placebo. As a result of the lack of separation in ADPS reduction between the 20 mg dose arm and placebo, the study results did not reach statistical significance on the primary endpoint (p=0.11). However, the 10 mg dose arm demonstrated clear evidence of effect by achieving early and clinically meaningful separation from placebo on ADPS that was maintained throughout the study duration.

Adverse events were more frequent in the pilavapadin treatment arms, but were significantly improved from the RELIEF-DPN-1 study across all doses. Nearly all adverse events were reported as mild or moderate. Adverse events were most prominent at the 20 mg dose and pilavapadin was generally well-tolerated at the 10 mg dose. Dizziness and nausea were the most commonly reported adverse events and the most frequently associated with patient discontinuations from the study, which occurred most predominantly in the 20 mg dose.

On the basis of the PROGRESS study results in the 10 mg dose arm, together with the previous findings from RELIEF-DPN-1, Lexicon has identified 10 mg once daily as an appropriate dose to advance into Phase 3 clinical development for DPNP.

Lexicon management will hold a live conference call and webcast today at 8:00 a.m. ET / 7:00 a.m. CT to review the details of this announcement. Participants can access the conference call live via webcast on the Events page of the Company’s website at https://investors.lexpharma.com/. Participants who wish to ask a question may register here to receive dial-in numbers and a unique pin to join the call. An archived version of the webcast will be available on the Lexicon website.

https://www.globenewswire.com/news-release/2025/03/03/3035469/0/en/Lexicon-Pharmaceuticals-Announces-Topline-Results-from-Phase-2b-PROGRESS-Study-Evaluating-Pilavapadin-LX9211-in-Adults-with-Diabetic-Peripheral-Neuropathic-Pain.html