Sanofi and Lexicon to continue any required studies in effort to move sotagliflozin forward.
Even though we have seen positive results for sotagliflozin being used with type 1 diabetes, allowing for the use of less insulin and lowering of the A1c results, the FDA Advisory Committee has decided not to approve the use of the dual SGLT-1/2 inhibitor for type 1 diabetes, according a press release from Sanofi and Lexicon. But it is not over and they will continue to discuss with the FDA any future studies they are required to do.
The FDA issues a complete response letter to an applicant if the agency determines that it will not approve the application or an abbreviated application in its present form for one or more reasons. Following a close vote from an FDA Advisory Committee, the FDA ultimately chose not to approve Zynquista, (sotagliflozin), issuing a Complete Response Letter (CRL) instead. The CRL includes the reason for not approving the SGLT-1/2 dual inhibitor for adults with type 1, but the document is not public. The next steps remain unclear, but the CRL could recommend a range of possibilities, from giving the FDA more time to evaluate the application to requiring additional clinical trials.
The main concern from the FDA, clinicians, and groups representing people with diabetes is the small but meaningfully increased chance of DKA (diabetic ketoacidosis), which likely contributed to the FDA’s decision not to approve Zynquista without more time and/or information. The CRL affirms the FDA’s commitment to ensuring patient safety and may highlight the need for added risk mitigation strategies. 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 said 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).
Many experts believe this class of medication fills a large gap in options for people with type 1 diabetes and can be safely taken with the right management and patient support. A comment from Dr. Chantal Mathieu, Professor of Medicine, KU Leuven in Belgium: “I respect the decision of FDA, but do not agree. As a clinician working with people with T1D, I realize every day the unmet needs with our current therapies: not reaching tight enough glycemic control because of increasing risk of hypoglycemia as HbA1c goes down, increasing weight and in particular instability of glucose values, with insufficient time in range. This class of SGLT inhibitors improves all of the above, with impressive increases in time in range of several hours a day! The increased risk of genital infections and the small, but real, increase in DKA is a problem we can overcome with the right education of both patients and medical teams. I am happy that the European Agency has seen this and has proposed a positive decision.”
- There are current studies ongoing to determine the use of dual SGLT-2/1 inhibitors for type 2 diabetes for patients taking insulin and or other diabetes medications.
- In patients who have type 1 diabetes, they were able to reduce the amount of insulin needed to manage blood sugars and reduce their A1c results.
- Even though there were positive results with the use of sotagliflozin, the increase in patients with diabetic ketoacidosis prevented a positive vote.
Lexicon and Sanofi announced the news in a joint press release.