Originally published HERE
The U.S. Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) today regarding Zynquista (sotagliflozin) for use by patients with Type 1 diabetes. Zynquista is a dual SGLT-1/2 inhibitor, and would have been the first oral medication approved for people with T1D to be used in conjunction with insulin therapy. Lexicon and Sanofi announced the news in a joint press release. In the statement, the partners said they’d “work closely with the FDA to determine the appropriate next steps.”
A CRL is issued when the FDA declines to approve a drug in its current form and has outstanding questions. It is not an outright rejection, but the responsibility now shifts back to the product sponsor(s) — in this case Lexicon and Sanofi who developed the drug — to address deficiencies raised.
SGLT inhibitors are not new to the diabetes landscape — SGLT-2 inhibitors have been used since 2013 in the United States to treat Type 2 diabetes. In fact, people with Type 1 diabetes have been regulating their blood sugars with off-label use of the drugs for just as long.
Recognizable name brand SGLT-2 inhibitors include Farxiga, Invokana and Jardiance. Studies on their use in T1D patients show promising results, and Farxiga and Zynquista are currently being reviewed by the European Medicines Agency (EMA) for usage by people with T1D.
Trial results for Zynquista identified a notable reduction in HbA1c levels and increased time in range (between 70-180 mg/dl), but the risk of diabetic ketoacidosis (DKA) was noted to be substantially higher during all trials for the drug. The content of CRLs are rarely made public, but the reasoning behind the FDA’s decision is likely due in part to this increased risk of DKA.
Zynquista would have been the first medication of its kind approved for use in Type 1 diabetes. The only two drugs previously approved for use in T1D to lower blood sugar are insulin and pramlintide — both injectable.
It remains to be seen if Zynquista will be approved for people living with T1D in Europe, but the preliminary recommendations from the Committee for Medicinal Products for Human Use (CHMP) in Europe were considerably more positive than the recommendations from the FDA Advisory Committee in the U. S.