Lexicon Set to Resubmit Zynquista for Type 1 Diabetes Treatment, 5 Years After FDA Rejection

Since its initial rejection by the FDA approximately five years ago, Lexicon Pharmaceuticals has remained steadfast in its commitment to advancing sotagliflozin as a viable treatment option for Type 1 diabetes. As the possibility of regulatory approval inches closer, the company is gearing up to resubmit its application, bolstered by recent feedback from regulatory authorities.
In an official statement, Lexicon reiterated its dedication to propelling sotagliflozin forward, indicating its intent to file for reconsideration by the middle of the year. CEO Lonnel Coats voiced confidence in the drug’s potential, emphasizing the company’s ongoing efforts to effectively navigate the regulatory landscape.

Lexicon envisions sotagliflozin as an adjunct to insulin therapy for adults managing both Type 1 diabetes mellitus and chronic kidney disease, a vision detailed in its recent earnings presentation. Should it receive the green light, the drug will hit the market under the brand name Zynquista.
The company encountered its initial regulatory setback in 2019 when the FDA issued a complete response letter citing safety concerns following a tied advisory committee vote. The dissolution of its partnership with Sanofi in the aftermath of the rejection, coupled with challenges in trials targeting Type 2 diabetes, further complicated matters.
At the heart of the FDA’s reservations lies the perceived risk of diabetic ketoacidosis among patients combining insulin with Zynquista. Nevertheless, Lexicon contends that the manageable risks are outweighed by the pressing unmet needs of patients grappling with the disease.
Despite encountering obstacles in the United States, Zynquista garnered approval in Europe in 2019, supported by Lexicon’s substantial phase 3 data demonstrating its effectiveness in managing diabetes alongside chronic kidney disease when used alongside insulin.

The anticipated approval of Zynquista carries significant implications for Lexicon, particularly in light of its modest revenues and substantial net losses in 2023. While initial expectations for the drug were ambitious, securing regulatory approval would serve as validation of Lexicon’s steadfast dedication to its development.
Lexicon has expanded the potential applications of sotagliflozin, obtaining approval for heart failure under the brand Inpefa last year. Its swift market entry marked a milestone as the first SGLT1/SGLT2 inhibitor to launch in the U.S. market. Additionally, ongoing exploration of sotagliflozin’s efficacy in hypertrophic cardiomyopathy underscores Lexicon’s holistic approach to maximizing the drug’s therapeutic impact.