The investigative SGLT1/2 dual inhibitor is scheduled to be considered for marketing approval by mid-March.
This week, a US Food and Drug Administration (FDA) advisory committee evenly split votes on the recommendation of sotagliflozin (Zynquista) for the approval as an adjunct to insulin for adults with type 1 diabetes (T1D).
The 8-8 vote from the Endocrinologic and Metabolic Drugs Advisory Committee was the first time the committee had split votes since 2010, when the panel voted 5 in favor, 5 against, and 2 abstained for the safety of carglumic acid tablets (CARBAGLU) for the specific treatment of hyperammonemia due to the deficiency of the hepatic enzyme N-acetylglutamate synthase (NAGS deficiency).
Despite the 2010 divide, discussion among the panel led to a consensus that the tablets appeared safe on a short-term basis, according to archived meeting minutes provided on the FDA's website. In the instance of sotagliflozin for adults with T1D, panel discussion was less conclusive. The committee was expressly concerned with the association of sodium-glucose Cotransporter-2 (SGLT2) inhibitors to increased risk of diabetic ketoacidosis (DKA).
Sotagliflozin is an oral small molecule compound therapy currently under joint development by Lexicon Pharmaceuticals and Sanofi for the treatment of T1D and type 2 diabetes mellitus. It also inhibits SGLT1, a transporter involved with the absorption of glucose and galactose in the gastrointestinal tract.
In primary efficacy endpoint data from September 2016—and additional data from May 2017— from the pivotal inTandem 1 phase 3 clinical trial assessing the therapy for glycemic parameters in patients with T1D, patients administered sotagliflozin in combination with insulin over 24 weeks achieved statistically significant benefit for hemoglobin A1C reduction versus placebo.
In assessing for adverse events over a 52-week treatment period, investigators noted that 20 (7.6%) of treated patients on either 200 mg or 400 mg sotagliflozin had positively adjudicated DKA events.
In a statement responding to the split advisory committee vote, Pablo Lapuerta, MD, executive vice president and chief medical officer of Lexicon, referred to both the positive and concerning findings of the pivotal trial.
“These results could not be achieved with insulin alone,” Lapuerta said. “Diabetic ketoacidosis is an inherent risk of type 1 diabetes and an increase was seen with sotagliflozin compared to insulin alone. We believe this can potentially be addressed with proper education and monitoring.”
That said, Rachele Berria, MD, PhD, global vice president and head of Diabetes Medical Affairs for Sanofi, maintained the belief that sotagliflozin has a positive benefit-risk profile for adults with T1D lacking adequate glycemic control on lone insulin.
“We will continue to work with the FDA through its review process to hopefully bring to patients a new treatment that can help people living with type 1 diabetes control their blood sugar and address some of the challenges of insulin-only therapy,” Berria said.
The FDA will make its decision on the therapy’s marketing application by March 22. Though it is not required to follow the direction of the committee’s vote, the panel’s findings are generally considered in the decision process.
It will be interesting to see what a split vote means for the therapy’s future.