Lexicon Pharmaceuticals Presents Additional Pilavapadin Data in Diabetic Peripheral Neuropathic Pain at 19th Annual Pain Therapeutics Summit

Rhea-AI Summary

Lexicon Pharmaceuticals (Nasdaq: LXRX) presented additional Phase 2 pilavapadin data for diabetic peripheral neuropathic pain (DPNP) on Oct 14, 2025. Analyses support advancing a 10 mg once-daily dose into Phase 3 and a U.S. FDA end-of-Phase 2 meeting request has been accepted.

The pooled post-hoc analysis covered >600 patients from RELIEF-DPN 1 and PROGRESS, reported a 2-point average daily pain score (ADPS) reduction at 12 weeks for 10 mg, showed a linear exposure-response relationship, found an acceptable safety and tolerability profile, and noted lower adherence and increased tolerability symptoms in the PROGRESS 20 mg arm. A slide deck is available on the company events page.

Positive

• End-of-Phase 2 meeting request accepted by FDA
• Pooled enrollment >600 patients across Phase 2 studies
• 2-point ADPS reduction from baseline at 12 weeks for 10 mg
• Linear exposure-response relationship supporting 10 mg
• Safety/tolerability profile comparable to placebo

Negative

• 20 mg arm showed lack of efficacy in PROGRESS
• Lower adherence in 20 mg participants tied to tolerability

Insights

Clinical development strategist

Data support 10 mg pilavapadin moving to Phase 3; FDA accepted an end-of-Phase 2 meeting and partnership talks are underway.

Lexicon presents pooled Phase 2 analyses showing a clear exposure-response link and a 2-point average daily pain score reduction at 12 weeks for the 10 mg dose, with tolerability and safety described as placebo-like and consistent with standard of care. The company reports >600 pooled patients across studies, post-hoc analyses addressing the non‑response at 20 mg, and additional PK and QTc assessments that the company says do not raise safety concerns.

The FDA acceptance of an end-of-Phase 2 meeting is a concrete regulatory step that enables alignment on Phase 3 design and endpoints; however, the conclusions rely on pooled and post-hoc analyses rather than a single prospective positive trial. Key dependencies and risks include the robustness of the pooled findings when pre-specified in Phase 3, confirmation of the 2-point ADPS reduction in a randomized pivotal setting, and whether tolerability differences at higher doses affect adherence. Monitor the timing and outcome of the FDA meeting, the finalized Phase 3 protocol and endpoints, and any disclosed partner term sheets over the next 6–12 months (6 months–12 months).

– Results support advancement of 10 mg dose into Phase 3 development –

– End-of-Phase 2 meeting request accepted by U.S. FDA; partnership discussions progressing –

THE WOODLANDS, Texas, Oct. 14, 2025 (GLOBE NEWSWIRE) -- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) today announced the Company presented additional clinical data and program updates from its Phase 2 pilavapadin program at the 19th Annual Pain Therapeutics Summit.

These data follow the topline results from the Phase 2b PROGRESS study of pilavapadin in diabetic peripheral neuropathic pain (DPNP) announced in March of 2025, which identified 10 mg once daily as the most clinically meaningful and appropriate dose to advance into Phase 3 development.

“Following the release of topline results from our PROGRESS study earlier this year, we performed additional analyses of the Phase 2 program data that support Phase 3 readiness of the 10mg dose of pilavapadin for DPNP. With these additional analyses, we have submitted an end-of-Phase 2 meeting with the U.S. FDA,” said Mike Exton, Ph.D., chief executive officer and director of Lexicon. “Our request has been accepted by the FDA and, in tandem, we are actively progressing discussions with potential partners.”

The additional analyses from the Phase 2 program resulted in four primary conclusions by the company with respect to the 10mg dose of pilavapadin:

1. Validated biological activity, as evidenced by a linear relationship between increased plasma levels of pilavapadin and pain reduction​.
2. Clinically meaningful efficacy, with a 2-point average daily pain score (ADPS) reduction from baseline at 12 weeks.
3. Acceptable tolerability profile, with placebo-like treatment completion rates.
4. Acceptable safety profile in line with standard of care, further bolstered by subsequent studies showing no prolonged QTc interval with pilavapadin treatment and no significant impact on the pharmacokinetics (PK) of pilavapadin from mild to moderately impaired renal function.

The data presentation included results from a post-hoc, pooled analysis of the Phase 2 RELIEF-DPN 1 and Phase 2b PROGRESS studies, which collectively enrolled more than 600 patients, designed to investigate the exposure-response relationship across the two Phase 2 studies, investigate the lack of efficacy of the 20 mg dose in the PROGRESS study, and confirm the robustness of the 10 mg dose for Phase 3 studies. Participants in the PROGRESS 20 mg dose arm were less adherent than participants in the other study arms, potentially driven by increased tolerability symptoms among patients receiving the 20mg dose and potentially driving the lack of observed dose response in that arm.

The slide presentation from the 19^th Annual Pain Therapeutics Summit is available on the Events page of the Company’s website at https://investors.lexpharma.com/.

About Pilavapadin
Discovered using Lexicon’s unique approach to gene science, pilavapadin (LX9211) is a potent, once-daily, orally delivered, selective, investigational small molecule inhibitor of AAK1, a novel target for neuropathic pain which inhibits reuptake and recycling of neurotransmitters involved in pain signaling without affecting opiate pathways. Lexicon identified AAK1 in its target discovery efforts as a promising approach for the treatment of neuropathic pain. Preclinical studies of pilavapadin demonstrated central nervous system penetration and reduction in pain behavior in models of neuropathic pain without affecting opiate pathways.

About Lexicon Pharmaceuticals
Lexicon is a biopharmaceutical company with a mission of pioneering medicines that transform patients’ lives. Through the Genome5000™ program, Lexicon’s unique genomics target discovery platform, Lexicon scientists studied the role and function of nearly 5,000 genes and identified more than 100 protein targets with significant therapeutic potential in a range of diseases. Through the precise targeting of these proteins, Lexicon is pioneering the discovery and development of innovative medicines to treat disease safely and effectively. Lexicon has a pipeline of promising drug candidates in discovery and clinical and preclinical development in neuropathic pain, hypertrophic cardiomyopathy (HCM), obesity, metabolism and other indications. For additional information, please visit www.lexpharma.com.

For Investor and Media Inquiries: 
Lisa DeFrancesco
Lexicon Pharmaceuticals, Inc.
lexinvest@lexpharma.com 

FAQ

What did Lexicon (LXRX) announce about pilavapadin on October 14, 2025?

Lexicon presented additional Phase 2 data supporting advancement of 10 mg once daily pilavapadin into Phase 3 and said the FDA accepted its end-of-Phase 2 meeting request.

Why is Lexicon advancing the 10 mg pilavapadin dose to Phase 3 (LXRX)?

A pooled analysis across >600 patients showed a linear exposure-response and a 2-point ADPS reduction at 12 weeks for the 10 mg dose.

What safety and tolerability findings did Lexicon report for pilavapadin (LXRX)?

The company reported an acceptable safety profile, placebo-like treatment completion rates, no prolonged QTc, and no significant PK impact from mild-moderate renal impairment.

What issue was observed with the 20 mg pilavapadin dose in the PROGRESS study (LXRX)?

The 20 mg arm lacked observed efficacy and had lower adherence, possibly driven by increased tolerability symptoms.

Has Lexicon secured FDA alignment for pilavapadin Phase 3 design (LXRX)?

Lexicon said its end-of-Phase 2 meeting request was accepted by the FDA, a step toward Phase 3 alignment.

Where can investors find the pilavapadin presentation from Oct 14, 2025 (LXRX)?

The slide presentation is available on the company’s Events page at the investor website.