Perspective

FDA issues complete response letter for sotagliflozin

The FDA on Friday issued a complete response letter regarding a new drug application for oral sotagliflozin, a first-in-class dual SGLT1 and SGLT2 inhibitor for adult with type 1 diabetes, according a press release from Sanofi and Lexicon.

The FDA issues a complete response letter to an applicant if the agency determines that it will not approve the application or abbreviated application in its present form for one or more reasons.

In January, the Endocrinologic and Metabolic Drugs Advisory Committee voted 8-8 in a decision on whether to recommend approval of sotagliflozin (Zynquista), with several members expressing concerns about an observed risk in diabetic ketoacidosis and calling for a risk evaluation and mitigation strategy if the therapy is approved.

In discussion following the split decision, committee members who voted both in favor of and against approving the drug cited similar concerns about incidence of diabetic ketoacidosis (DKA) observed across three phase 3 trials, which the FDA noted was the most notable and concerning adverse reaction associated with sotagliflozin. In agency analyses, sotagliflozin was associated with an approximately eightfold increase in DKA risk vs. placebo (95% CI, 3.1-19.9). The estimated number needed to harm was approximately 26 patient-years of exposure to sotagliflozin to observe 1 additional DKA event, according to the FDA (95% CI, 20.1-38.5)

In the release, Sanofi and Lexicon stated they will work closely with the FDA to determine the appropriate next steps. – by Regina Schaffer

The FDA on Friday issued a complete response letter regarding a new drug application for oral sotagliflozin, a first-in-class dual SGLT1 and SGLT2 inhibitor for adult with type 1 diabetes, according a press release from Sanofi and Lexicon.

The FDA issues a complete response letter to an applicant if the agency determines that it will not approve the application or abbreviated application in its present form for one or more reasons.

In January, the Endocrinologic and Metabolic Drugs Advisory Committee voted 8-8 in a decision on whether to recommend approval of sotagliflozin (Zynquista), with several members expressing concerns about an observed risk in diabetic ketoacidosis and calling for a risk evaluation and mitigation strategy if the therapy is approved.

In discussion following the split decision, committee members who voted both in favor of and against approving the drug cited similar concerns about incidence of diabetic ketoacidosis (DKA) observed across three phase 3 trials, which the FDA noted was the most notable and concerning adverse reaction associated with sotagliflozin. In agency analyses, sotagliflozin was associated with an approximately eightfold increase in DKA risk vs. placebo (95% CI, 3.1-19.9). The estimated number needed to harm was approximately 26 patient-years of exposure to sotagliflozin to observe 1 additional DKA event, according to the FDA (95% CI, 20.1-38.5)

In the release, Sanofi and Lexicon stated they will work closely with the FDA to determine the appropriate next steps. – by Regina Schaffer

    Perspective
    Anne L. Peters

    Anne L. Peters

    This was not a huge surprise because the FDA advisory committee did not seem to go wildly in their favor — half the panel voted against recommending approval. However, the members who voted in favor of approval were the endocrinologist clinicians who work closely with patients with diabetes. I really think that sotagliflozin should come to market for people with type 1 diabetes. We’ll see what the whole letter shows, but my advice is for the companies to convince the FDA that this drug provides more than a numeric benefit. You cannot just look at the HbA1c. They should also create a very careful risk evaluation and mitigation strategy (REMS) to conduct, in essence, phase 4 monitoring looking at what happens if approved.

    I hope they can do both of those things: Convince the FDA that this drug really meets an unmet need and is good for patients with type 1 diabetes, and create a REMS that makes it safe in terms of follow-up. Perhaps roll this out for endocrinologists first, using it in a very specific way until they get more practice with it. I hope this doesn’t mean the end of it. I believe sotagliflozin is a good drug, and I hope the FDA lets the company make a better case for it.

    • Anne L. Peters, MD
    • Endocrine Today Editorial Board Member
      Professor of Clinical Medicine
      Keck School of Medicine, University of Southern California, Los Angeles

    Disclosures: Peters reports various financial ties with Abbott, Becton Dickinson, Bigfoot, Boehringer Ingelheim, Dexcom, Eli Lilly, Janssen, Lexicon, Livongo, Medscape, Merck, Novo Nordisk, Omada Health, Sanofi and Science 37.