Lexicon Completes SONATA-HCM Enrollment, Eyes 2027 Sotagliflozin Data

Key Points

• Lexicon completed enrollment in its Phase III SONATA-HCM trial of sotagliflozin, enrolling more than the planned 500 patients across obstructive and non-obstructive hypertrophic cardiomyopathy. Topline results are expected in the first quarter of 2027.
• The company has begun pre-launch planning for HCM, including adding commercial and medical-affairs staff, and sees potential for an oral, once-daily treatment—particularly for non-obstructive HCM, where Lexicon says approved options are limited.
• Lexicon plans to resubmit sotagliflozin for type 1 diabetes in the fourth quarter after supportive STENO1 data, with a possible FDA decision in 2027. It also reported milestone payments from Novo Nordisk and is preparing a potential Phase III program for pilavapadin in diabetic neuropathic pain.

Lexicon Pharmaceuticals NASDAQ: LXRX said it has completed enrollment in its Phase III SONATA-HCM study of sotagliflozin in hypertrophic cardiomyopathy, with topline data expected in the first quarter of 2027.

Speaking at the H.C. Wainwright 28th Annual Global Investment Conference, Chief Executive Officer Dr. Mike Exton said the company is continuing its transition toward a cardiometabolic focus, with sotagliflozin programs in hypertrophic cardiomyopathy, or HCM, and type 1 diabetes among its principal near-term priorities.

SONATA-HCM Enrollment Exceeds Target

Exton said SONATA-HCM was designed to enroll 500 patients across obstructive and non-obstructive forms of HCM, but the trial ultimately “substantially over-enrolled” that target. Enrollment was completed at the end of July, and the 26-week study uses the Kansas City Cardiomyopathy Questionnaire, or KCCQ, as an endpoint.

The company expects to present baseline demographic information from the trial at an HCM-focused medical meeting after the data are cleaned, Exton said.

Lexicon executives emphasized their view that obstructive and non-obstructive HCM represent a continuum rather than wholly separate diseases. Exton said diastolic dysfunction and left ventricular hypertrophy are central features across the condition, while the distinction between obstructive and non-obstructive disease primarily reflects the location of heart-muscle thickening.

Chief Medical Officer Dr. Craig Granowitz said HCM has historically been defined in part by available treatments, including surgery and therapies that reduce cardiac contractility. He said sotagliflozin is intended to act through multiple mechanisms, including SGLT2-related cardiorenal and decongestion effects as well as potential direct effects on myocardial energetics through SGLT1.

According to Granowitz, SONATA-HCM has broad inclusion criteria, including patients with ejection fractions as low as 50%. The study also permits certain patients using cardiac myosin inhibitors, or CMIs, subject to entry criteria. He contrasted that approach with CMI use in patients with more hyperdynamic heart function.

Commercial Planning and HCM Positioning

Exton said Lexicon has begun pre-launch planning for a potential HCM commercialization effort. The company promoted Rachel Martens, previously responsible for partnership and strategy activities, to chief commercial officer. Lexicon also hired a head of marketing, a head of access and five medical science liaisons, he said.

The company is conducting market research on the potential positioning of sotagliflozin. Exton said physicians have identified an unmet need in non-obstructive HCM, where he said there are currently no approved treatment options.

He said the company believes sotagliflozin could provide an oral, once-daily treatment option with potential use across both obstructive and non-obstructive disease, depending on study results and regulatory decisions. Exton also cited the drug’s existing heart-failure safety record and said its potential profile could differ from currently approved CMIs, which can require risk-management procedures related to potential reductions in ejection fraction.

Type 1 Diabetes Resubmission Planned

In type 1 diabetes, Exton said the third-party STENO1 study has completed the recruitment and drug-exposure requirements Lexicon believes are needed to support a U.S. Food and Drug Administration resubmission for sotagliflozin.

He said STENO1 is an open-label Danish cardiovascular outcomes study and that observed diabetic ketoacidosis, or DKA, rates in the sotagliflozin group have been similar to standard of care and lower than rates observed in Lexicon’s prior inTandem program. The company plans to resubmit its application in the fourth quarter and said a potential FDA decision could occur in 2027.

Partnership and Pipeline Updates

Exton also discussed Lexicon’s partnerships with Viatris and Novo Nordisk. Viatris has submitted and received approvals for sotagliflozin in the United Arab Emirates and Bahrain for heart failure, he said, while additional submissions in markets outside the U.S. and European Union are continuing.

For LX9851, Lexicon’s non-incretin obesity mechanism partnered with Novo Nordisk, Exton said Lexicon has received three $10 million milestone payments this year, in addition to $45 million received in the prior year. He said the agreement carries up to $1 billion in potential milestone payments, along with high-single-digit to low-double-digit sales royalties.

Lexicon is also preparing for a potential Phase III program for pilavapadin in diabetic peripheral neuropathic pain and plans to present additional preclinical information later this year regarding AAK1 biology and potential further indications, Exton said.

About Lexicon Pharmaceuticals (NASDAQ:LXRX)

Lexicon Pharmaceuticals, Inc is a biopharmaceutical company that discovers and develops medicines for human disease. Founded in 1995 and headquartered in The Woodlands, Texas, the company uses its drug-discovery platform and expertise in biology to identify potential treatments for conditions with significant unmet medical needs.

Lexicon's marketed products include XERMELO (telotristat ethyl), an oral medicine used to treat carcinoid syndrome diarrhea in adults whose symptoms are not adequately controlled by somatostatin analog therapy.

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