Pilavapadin Provides Meaningful Pain Reduction in Adults with Diabetic Peripheral Neuropathic Pain (DPNP) in Data Presented at the European Association for the Study of Diabetes (EASD) and NEUROdiab Annual Meetings
Rhea-AI Summary
Lexicon Pharmaceuticals (NASDAQ:LXRX) presented promising clinical data for pilavapadin, its investigational AAK1-inhibitor for diabetic peripheral neuropathic pain (DPNP), at two major medical conferences. The Phase 2b PROGRESS study demonstrated that pilavapadin 10 mg achieved a significant two-point reduction in average daily pain scores by week 11.
The study evaluated various dosing regimens, with the 10 mg daily dose emerging as the most clinically meaningful option, showing nominally significant separation from placebo (p 0.05)first non-opioid, oral medication approved for DPNP in over 20 years, addressing a significant market of approximately 9 million U.S. patients.
Positive
- Pilavapadin 10mg achieved significant pain reduction with p < 0.05 vs placebo
- Drug demonstrated strong safety profile with minimal discontinuations
- Addresses large market of 9 million U.S. patients with DPNP
- Could be first non-opioid oral DPNP treatment approved in over 20 years
Negative
- Still in Phase 2b, requiring additional Phase 3 trials before potential approval
News Market Reaction
On the day this news was published, LXRX declined 0.91%, reflecting a mild negative market reaction. Argus tracked a peak move of +9.3% during that session. Our momentum scanner triggered 30 alerts that day, indicating elevated trading interest and price volatility. This price movement removed approximately $4M from the company's valuation, bringing the market cap to $452M at that time. Trading volume was elevated at 2.8x the daily average, suggesting increased selling activity.
Data tracked by StockTitan Argus on the day of publication.
Pilavapadin 10 mg resulted in a two-point reduction from baseline in average daily pain scores (ADPS) by week 11 and was well tolerated in PROGRESS Phase 2b study
THE WOODLANDS, Texas, Sept. 17, 2025 (GLOBE NEWSWIRE) -- 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
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.
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 the PROGRESS Study
The PROGRESS study commenced in December 2023 and enrolled 496 adult patients with a diagnosis of diabetes (type 1 or type 2) and moderate to severe DPNP. The study was placebo-controlled with a primary endpoint of change from baseline to Week 8 in ADPS as compared to placebo and evaluated three treatment groups receiving once daily pilavapadin doses of 10 mg, 20 mg or 20 mg for seven days followed by 10 mg thereafter. Secondary endpoints included change from baseline to Week 8 in burning pain and pain interference on sleep. Study design permitted patients to remain on one stable-dose DPNP therapy (e.g. gabapentin, pregabalin or duloxetine) without withdrawing from therapies that, although inadequate, may be providing some benefit – aligning with how new DPNP drugs are likely to be used in practice.
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.
Safe Harbor Statement
This press release contains “forward-looking statements,” including statements relating to Lexicon’s financial position and long-term outlook on its business, including the commercialization of its approved products and the clinical development of, regulatory filings for, and potential therapeutic and commercial potential of pilavapadin and its other drug candidates. In addition, this press release also contains forward looking statements relating to Lexicon’s growth and future operating results, discovery, development and commercialization of products, strategic alliances and intellectual property, as well as other matters that are not historical facts or information. All forward-looking statements are based on management’s current assumptions and expectations and involve risks, uncertainties and other important factors, specifically including Lexicon’s ability to meet its capital requirements, successfully commercialize its approved products, successfully conduct preclinical and clinical development and obtain necessary regulatory approvals of its other drug candidates on its anticipated timelines, achieve its operational objectives, obtain patent protection for its discoveries and establish strategic alliances, as well as additional factors relating to manufacturing, intellectual property rights, and the therapeutic or commercial value of its approved products and other drug candidates. Any of these risks, uncertainties and other factors may cause Lexicon’s actual results to be materially different from any future results expressed or implied by such forward-looking statements. Information identifying such important factors is contained under “Risk Factors” in Lexicon’s annual report on Form 10-K for the year ended December 31, 2024, as filed with the Securities and Exchange Commission. Lexicon undertakes no obligation to update or revise any such forward-looking statements, whether as a result of new information, future events or otherwise.
For Investor and Media Inquiries:
Lisa DeFrancesco
Lexicon Pharmaceuticals, Inc.
lexinvest@lexpharma.com
FAQ
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