The Food and Drug Administration (FDA) has accepted for review the New Drug Application (NDA) for sotagliflozin for the treatment of heart failure (HF).

Sotagliflozin is an investigational dual sodium-glucose co-transporter types 1 and 2 (SGLT1, SGLT2) inhibitor. The Company is seeking approval for 2 indications:

  • To reduce the risk of cardiovascular (CV) death, hospitalization for HF, and urgent HF visit in adults with HF, including those with acute or worsening HF.
  • To reduce the risk of CV death, hospitalization for HF, urgent HF visit, nonfatal myocardial infarction, and nonfatal stroke in adults with type 2 diabetes mellitus, chronic kidney disease, and other CV risk factors, including a history of HF.

The NDA is supported by data from the multicenter, randomized, double-blind, placebo-controlled phase 3 SOLOIST-WHF (ClinicalTrials.gov Identifier: NCT03521934) and SCORED (ClinicalTrials.gov Identifier: NCT03315143) studies.

SOLOIST-WHF evaluated the CV efficacy of sotagliflozin in 1222 hemodynamically stable adults with type 2 diabetes who had recently been hospitalized for worsening HF. SCORED evaluated the CV efficacy of sotagliflozin in 10,584 adults with type 2 diabetes, chronic kidney disease with an estimated glomerular filtration rate of 25 to 60mL/min/1.73m2 of BSA, and risks for CV disease. 

Patients were randomly assigned to receive sotagliflozin or placebo orally once daily, in addition to standard of care. The primary endpoint for both studies was the total occurrences (first and potentially subsequent) of CV death, hospitalization for HF, and urgent HF visits after randomization.

In SOLOIST-WHF, the number of primary endpoint events per 100 patient-years was 51.0 in the sotagliflozin arm and 76.3 in the placebo arm (hazard ratio [HR], 0.67; 95% CI, 0.52-0.85; P <.001). In SCORED, the number of primary endpoint events per 100 patient-years was 5.6 in the sotagliflozin arm and 7.5 in the placebo arm (HR, 0.74; 95% CI, 0.63-0.88; P <.001). The overall tolerability profile of sotagliflozin was similar to that observed with placebo in both studies.

“Informed by our regulatory discussions, we are seeking a broad heart failure label in the NDA encompassing heart failure patients with and without diabetes, and believe that the results of SOLOIST-WHF in patients admitted for recent worsening heart failure will be an important element distinguishing our proposed label,” said Lonnel Coats, Lexicon’s chief executive officer. “We look forward to engaging with the FDA during the review process to bring this potential new treatment to market by the middle of next year.”

A Prescription Drug User Fee Act (PDUFA) target action date in May 2023 has been set for the application.

References

  1. Lexicon announces FDA acceptance of New Drug Application for sotagliflozin to treat heart failure. News release. Lexicon Pharmaceuticals, Inc. Accessed July 27, 2022. https://www.globenewswire.com/news-release/2022/07/27/2486783/0/en/Lexicon-Announces-FDA-Acceptance-of-New-Drug-Application-for-Sotagliflozin-to-Treat-Heart-Failure.html
  2. Bhatt DL, Szarek M, Steg G, et al. Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure. N Engl J Med. Published online January 14, 2021. doi:10.1056/NEJMoa2030183
  3. Bhatt DL, Szarek M, Pitt B, et al. Sotagliflozin in Patients with Diabetes and Chronic Kidney Disease. N Engl J Med. Published online January 14, 2021. doi:10.1056/NEJMoa2030186