Lexicon Pharmaceuticals, Inc. operates as a biopharmaceutical company.
The company is developing pilavapadin (LX9211), an orally-delivered small molecule drug candidate, as a treatment for neuropathic pain. The company has completed three Phase 2 clinical trials evaluating the safety and tolerability of pilavapadin and its effects on diabetic peripheral neuropathic pain (DPNP) and neuropathic pain. The company has reported top-line results from its Phase 2b clinical trial of pilavapadin in DPNP...
Lexicon Pharmaceuticals, Inc. operates as a biopharmaceutical company.
The company is developing pilavapadin (LX9211), an orally-delivered small molecule drug candidate, as a treatment for neuropathic pain. The company has completed three Phase 2 clinical trials evaluating the safety and tolerability of pilavapadin and its effects on diabetic peripheral neuropathic pain (DPNP) and neuropathic pain. The company has reported top-line results from its Phase 2b clinical trial of pilavapadin in DPNP, which demonstrated clear evidence of effect at the 10 mg dose, and has received Fast Track designation from the U.S. Food and Drug Administration (FDA) for the development of pilavapadin in that indication. The company has also reported positive results from a Phase 2a clinical trial of pilavapadin in DPNP, and results from a separate Phase 2a clinical trial of pilavapadin in post-herpetic neuralgia, which also demonstrated evidence of effect.
The company is developing LX9851, an orally-delivered small molecule drug candidate, as a treatment for obesity and associated cardiometabolic disorders, and is conducting preclinical development of LX9851 in preparation for filing an investigational new drug application (IND) with the FDA.
The company is commercializing INPEFA (sotagliflozin), an orally-delivered small molecule drug, in the United States to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visits in adults with heart failure, type 2 diabetes mellitus, chronic kidney disease (CKD), and other cardiovascular risk factors.
The company is also developing sotagliflozin as a treatment for hypertrophic cardiomyopathy (HCM), and is conducting a Phase 3 clinical trial of sotagliflozin in that indication.
The company is separately pursuing regulatory approval of ZYNQUISTA (sotagliflozin) as a treatment for type 1 diabetes. The FDA issued a complete response letter regarding the company’s New Drug Application (NDA) for sotagliflozin in type 1 diabetes in March 2019, and an additional complete response letter in December 2024 regarding its NDA for sotagliflozin as an adjunct to insulin therapy for glycemic control in adults with type 1 diabetes and CKD. At the company’s request, the FDA has issued a public Notice of Opportunity for Hearing (NOOH) on whether there are grounds for denying approval of the company’s NDA, and those proceedings are ongoing.
The company is conducting preclinical research and development of compounds from a number of additional drug programs originating from its internal drug discovery efforts.
Pilavapadin originated from the company’s collaborative neuroscience drug discovery efforts with Bristol-Myers Squibb, and LX9851, sotagliflozin, as well as compounds from a number of additional drug programs originated from the company’s own internal drug discovery efforts. The company’s efforts were driven by a systematic, target biology-driven approach, in which it used gene knockout technologies and an integrated platform of advanced medical technologies to systematically study the physiological and behavioral functions of almost 5,000 genes in mice, and assessed the utility of the proteins encoded by the corresponding human genes as potential drug targets. The company has identified and validated in living animals (in vivo), more than 100 targets with promising profiles for drug discovery.
The company has worked both independently and through collaborations and strategic alliances with third parties to capitalize on its drug target discoveries and research and development programs. The company seeks to retain exclusive or co-exclusive rights to the benefits of certain research and development programs by developing and commercializing drug candidates from those programs internally, particularly in the United States for indications treated by specialist physicians. The company seeks to collaborate with other pharmaceutical and biotechnology companies with respect to the research, development, and commercialization of certain of its drug candidates, particularly with respect to commercialization in territories outside the United States, or commercialization in the United States for indications treated by primary care physicians, or when the collaboration may otherwise provide it with access to expertise and resources that it does not possess internally, or are complementary to its own.
Drugs and Drug Candidates
The company is devoting most of its resources to the research and development of pilavapadin, LX9851, and sotagliflozin, and the commercialization of INPEFA. The company has also advanced a number of additional compounds into various stages of preclinical research and development.
Pilavapadin (LX9211)
Pilavapadin is an orally-delivered small molecule compound that the company is developing as a treatment for neuropathic pain. The company has received Fast Track designation from the FDA for the development of pilavapadin in DPNP. The company’s scientists identified the target of pilavapadin, adapter-associated kinase 1 (AAK1), in its target discovery efforts based on their discovery that mice lacking AAK1 exhibited increased resistance to induced neuropathic pain in preclinical models. Pilavapadin and another development candidate were discovered by scientists working within its drug discovery alliance with Bristol-Myers Squibb, from which the company holds exclusive development and commercialization rights. Preclinical studies of pilavapadin demonstrated central nervous system penetration and reduction in pain behavior in models of neuropathic pain without affecting opiate pathways.
The company has completed three Phase 2 clinical trials evaluating the safety and tolerability of pilavapadin and its effects on DPNP and neuropathic pain.
The company’s PROGRESS Phase 2b clinical trial enrolled 496 patients with type 1 or type 2 diabetes experiencing moderate to severe DPNP in a randomized, double-blind, placebo-controlled study evaluating three treatment groups receiving once daily pilavapadin doses of 10 mg, 20 mg, or 20 mg for seven days followed by 10 mg thereafter. The effects of pilavapadin were assessed over a 16-week evaluation period, which included a screening period of two weeks and a blinded evaluation period of 14 weeks. The primary efficacy endpoint under evaluation in the study was the reduction in an average daily pain score (ADPS) from baseline to Week 8 as compared to placebo, with secondary endpoints, including reduction in burning pain, and reduction in pain interference on sleep at 8 weeks. Certain patient-reported outcome measures were also assessed. Topline data from the study showed a reduction in 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 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. 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. No drug-related serious adverse events or deaths were reported in the study.
The company’s RELIEF-DPN-1 Phase 2 clinical trial enrolled 319 patients experiencing DPNP in a randomized, double-blind, placebo-controlled study of pilavapadin evaluating three treatment groups receiving an initial loading dose of 100 mg or 200 mg of pilavapadin or placebo, followed by once daily doses of 10 mg or 20 mg of pilavapadin or placebo, respectively. The effects of pilavapadin were assessed over an 11-week evaluation period, which included a 5-week placebo run-off period following the initial 6-week treatment period. The primary efficacy endpoint under evaluation in the study was the change from baseline to week 6 in ADPS, based on the 11-point numerical rating scale in patients treated with pilavapadin compared with placebo. Data from the study showed a statistically significant reduction from baseline to week 6 in ADPS of 1.39 points in the low dose arm, compared to 0.72 in the placebo arm (p=0.007 versus placebo), meeting the study’s primary endpoint. The high dose arm demonstrated a reduction from baseline to week 6 in ADPS of 1.27 points (p=0.030 versus placebo), narrowly missing statistical significance. Consistent and statistically significant benefits in burning pain, pain interference with sleep, and other measures of particular importance in DPNP were also observed in both pilavapadin treatment arms as compared to placebo during the initial 6-week treatment period. During the blinded 5-week placebo run-off period, there was a gradual tapering of efficacy in both treatment arms, with no evidence of rebound pain or withdrawal symptoms.
Adverse events were more frequent in the pilavapadin treatment arms and at the higher dose during the initial 6-week treatment period, with the most common being dizziness, headache, and nausea, and nearly all being reported as mild or moderate.
The company’s RELIEF-PHN-1 Phase 2 clinical trial enrolled 79 patients experiencing post-herpetic neuralgia (PHN) in a randomized, double-blind, placebo-controlled study of pilavapadin evaluating two treatment groups receiving an initial loading dose of 200 mg of pilavapadin or placebo, followed by once daily doses of 20 mg of pilavapadin or placebo, respectively. The effects of pilavapadin were assessed over an 11-week evaluation period, which included a 5-week placebo run-off period following the initial 6-week treatment period. The primary efficacy endpoint under evaluation in the study was the change from baseline to week 6 in ADPS based on the 11-point numerical rating scale in patients treated with pilavapadin compared with placebo. Topline data from the study showed a reduction from baseline to week 6 in ADPS of 2.42 points in the pilavapadin arm, compared to a reduction of 1.62 points in the placebo arm (p=0.120 versus placebo), missing statistical significance in the study’s primary endpoint but demonstrating evidence of effect. Separation of pilavapadin from placebo on ADPS was observed at week 1 and maintained consistently thereafter, with an average placebo-adjusted reduction over the 6-week treatment period of 0.80 points (p=0.031 versus placebo). Adverse events were consistent with those observed in the company’s RELIEF-DPN-1 clinical trial, with dizziness as the most commonly reported and the most frequently associated with patient dropouts from the study. No drug-related serious adverse events or deaths were reported in the study.
LX9851
The company is developing LX9851, an orally-delivered small molecule drug candidate, for the treatment of obesity and as a tool for weight management. The company is conducting IND-enabling studies of the compound and its associated back-up molecules in preparation for filing an IND. The company’s scientists identified the target of LX9851 in its target discovery efforts based on their discovery that mice lacking such target exhibited favorable phenotypes across multiple measures of metabolic syndrome in preclinical models, including resistance to diet-induced obesity and improved body composition.
Sotagliflozin
Sotagliflozin is an orally-delivered small molecule compound that the company is commercializing for heart failure and developing for HCM and type 1 diabetes. The company’s scientists identified the targets of sotagliflozin, sodium-glucose cotransporter type 1 (SGLT1), and sodium-glucose cotransporter type 2 (SGLT2), in its target discovery efforts based on their discovery that mice lacking SGLT1, SGLT2, or both exhibited favorable phenotypes across multiple measures of metabolism and glucose control in preclinical models. Preclinical studies of sotagliflozin demonstrated that compounds inhibiting both targets had a favorable preclinical profile relative to compounds selective for SGLT2.
The company uses ‘INPEFA’ when referring to its FDA-approved drug, ‘sotagliflozin’ when referring to its development for HCM, and ‘ZYNQUISTA’ when referring to its development for type 1 diabetes.
Heart Failure
The company commercially launched INPEFA, a once-daily oral tablet, following regulatory approval in the United States in May 2023 to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visits in adults with heart failure or type 2 diabetes, CKD, and other cardiovascular risk factors.
In November 2024, the company restructured and significantly reduced its commercial operations for INPEFA, but it continues to manufacture and make INPEFA available to patients and prescribers. The company does not maintain a sales force for INPEFA. The company’s internal medical affairs function maintains responsibility for responding to external inquiries regarding the appropriate use of INPEFA, with regularly updated and well-substantiated scientific and medical information. The company principally sells INPEFA to a limited number of major wholesalers, as well as selected regional wholesalers, most of whom in turn resell INPEFA to retail pharmacies, hospitals, government agencies, and other institutions for subsequent resale to patients and healthcare providers.
Hypertrophic Cardiomyopathy
The company is conducting a Phase 3 clinical trial, SONATA HCM, evaluating the efficacy and safety of sotagliflozin and its effects on HCM. The trial is expected to enroll approximately 500 patients experiencing obstructive or non-obstructive HCM in a randomized, double-blind, placebo-controlled study of a 400 mg once daily dose of sotagliflozin over a 26-week treatment period. Doses for patients not tolerating treatment may be reduced to 200 mg beginning at week 4. The primary efficacy endpoint under evaluation will be change from baseline in the patient-reported Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score at 26 weeks, with secondary endpoints, including change in KCCQ total symptom score and New York Heart Association class improvement at 26 weeks.
Type 1 Diabetes
The FDA issued a complete response letter in March 2019 regarding the company’s NDA for ZYNQUISTA in type 1 diabetes, and confirmed that position in denying two appeals of the complete response letter in November 2019 and March 2020. The FDA issued an additional complete response letter in December 2024 regarding the company’s NDA for ZYNQUISTA as an adjunct to insulin therapy for glycemic control in adults with type 1 diabetes and CKD. At the company’s request, the FDA has issued a public NOOH on whether there are grounds for denying approval of its NDA, and those proceedings are ongoing.
Additional Research and Development Programs
The company is conducting preclinical research and development of compounds from a number of additional drug programs originating from its internal drug discovery efforts. The company has identified and validated in living animals (in vivo), more than 100 targets with promising profiles for drug discovery.
Collaborations and Strategic Alliances
Viatris
The company entered into an exclusive license agreement with Viatris Inc. in October 2024, under which it granted Viatris an exclusive, royalty-bearing right and license to develop and commercialize sotagliflozin in the licensed territory.
Bristol-Myers Squibb
The company established a drug discovery alliance with Bristol-Myers Squibb Company in December 2003 to discover, develop, and commercialize small molecule drugs in the neuroscience field. Bristol-Myers Squibb extended the target discovery term of the alliance in May 2006. The company initiated the alliance with a number of neuroscience drug discovery programs at various stages of development, and used its gene knockout technologies to identify additional drug targets with promise in the neuroscience field. For those targets that were selected for the alliance, the company and Bristol-Myers Squibb worked together, on an exclusive basis, to identify, characterize, and carry out the preclinical development of small molecule drugs. Bristol-Myers Squibb has the first option to assume full responsibility for clinical development and commercialization of any drugs resulting from the alliance which enter clinical trials, other than pilavapadin and additional compounds acting through AAK1, for which the company holds exclusive development and commercialization rights under the alliance.
Competition
The company’s principal competition for INPEFA for the treatment of heart failure includes dapagliflozin and empagliflozin, currently marketed for the treatment of heart failure by AstraZeneca, and through an alliance between Boehringer Ingelheim and Eli Lilly, respectively. Such competition also includes, to some extent, other classes of drugs used in the treatment of heart failure, such as the combination drug sacubitril/valsartan, currently marketed for the treatment of heart failure by Novartis, and vericiguat, marketed for the treatment of heart failure by Merck.
Government Regulation
Before commencing the first clinical trial of a drug candidate in the United States, the company must submit an IND to the FDA.
Other countries also have, or are developing, laws governing the collection, use, and transmission of personal information. In addition, most healthcare providers who are expected to prescribe the company’s products and from whom it obtains patient health information, are subject to privacy and security requirements under the Health Insurance Portability and Accountability Act of 1996, as amended by the Health Information Technology and Clinical Health Act (HIPAA).
The company is also required to discount such products to authorized users of the Federal Supply Schedule of the General Services Administration, under which additional laws and requirements apply.
In addition to the foregoing, the company’s business is subject to regulation under various state and federal environmental and worker safety laws, including the Occupational Safety and Health Act, the Resource Conservation and Recovery Act, the Comprehensive Environmental Response, Compensation and Liability Act, and the Toxic Substances Control Act, each as amended from time to time.
Patents and Proprietary Rights
The company owns or exclusively licenses patents and patent applications throughout the world that claim its drugs and drug candidates, including:
Issued patents and pending patent applications in Europe, the United States, and other countries throughout the world, including Australia, Brazil, Canada, China, Europe, India, Israel, Japan, Mexico, New Zealand, South Africa, and South Korea, that claim pilavapadin, crystalline forms of pilavapadin, pharmaceutical compositions comprising pilavapadin, and methods of its manufacture and use;
Pending United States and Patent Cooperation Treaty (PCT) patent applications that claim LX9851, pharmaceutical compositions comprising it, and methods of its manufacture and use; and
Issued patents and pending patent applications in Europe, the United States, and other countries throughout the world, including Australia, Argentina, Brazil, Canada, China, Europe, India, Israel, Japan, Mexico, New Zealand, South Africa, and South Korea, that claim sotagliflozin, crystalline forms of sotagliflozin, pharmaceutical compositions comprising sotagliflozin, and methods of its manufacture and use.
The normal life of a patent depends primarily on when it was filed. Patents granted in PCT member states typically expire 20 years after their earliest filing date. The actual protection afforded by a patent, which can vary from country to country, depends on the type of patent, the scope of its coverage, and the availability of legal remedies in the country. The company has filed patent applications and holds issued patents covering each of its drugs and drug candidates. None of the company’s United States patents that claim pilavapadin has a normal expiration date earlier than 2035. The earliest normal expiration date for any patent that issues from its applications claiming LX9851 is February 15, 2045. The earliest normal expiration date of its United States patents that claim sotagliflozin is 2028. However, the company has applied for an extension of patent term based on the FDA’s approval of the drug, and expects that upon acceptance of that application, an additional five years will be added to the term of a patent that claims sotagliflozin, pushing its expiration date out to 2033.
Trademark
The Lexicon name and logo, and INPEFA are registered trademarks of Lexicon Pharmaceuticals, Inc. ZYNQUISTA is a trademark of the company.
Research and Development
In 2024, the company incurred expenses of $84.5 million in company-sponsored, as well as collaborative research and development activities.
History
Lexicon Pharmaceuticals, Inc., a Delaware corporation, was founded in 1995. The company was incorporated in 1995.
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