FDA to Review SGLT1/2 Inhibitor Sotagliflozin as Possible Treatment for Type 1 Diabetes

The FDA has accepted the regulatory filing for sotagliflozin, an investigational dual inhibitor treatment that would be given with insulin to adults with type 1 diabetes (T1D).

Developed by Lexicon Pharmaceuticals, the joint filing with Sanofi seeks to market the oral therapy as Zynquista, based on results of the inTandem clinical trial programs, including 3 phase III trials. Results were reported last September at the European Association for the Study of Diabetes (EASD) in Lisbon, Portugal, and showed that the drug helped 28.6% of patients achieve glycated hemoglobin of 7.0% of less by week 24 without severe hypoglycemia or diabetic ketoacidosis.

“If approved, Zynquista would be the first oral antidiabetic drug approved in the US for use by adults with type 1 diabetes, in combination with insulin,” Jorge Insuasty, senior vice president and global head of development for Sanofi, said in a joint statement from the companies. “We look forward to working with the FDA through the review process with a view towards bringing this investigational medicine to adults with type 1 diabetes in the US.”

Sotagliflozin acts on both the sodium glucose co-transporter 1 and 2 proteins (SGLT1 and SGLT2), and, like the popular SGLT2 inhibitors that have been so successful in treating type 2 diabetes (T2D), the drug helped trial participants with T1D lose weight during the trial. Patients in the trial reported at EASD lost 2.98 kg more than those in the control arm, primarily because they needed less insulin. The drug works by targeting proteins involved in the process of recapturing glucose in the renal system; by blocking the protein, the body expels excess glucose in the urine.

“After decades of little change and innovation, the treatment of type 1 diabetes has begun to shift significantly and, if approved, our dual SGLT1 and SGLT2 inhibitor, Zynquista, would be the first approved oral therapy used in combination with insulin to improve glycemic control and patient outcomes for adults in the United States who are living with type 1 diabetes,” said Pablo Lapuerta, MD, executive vice president and chief medical officer, Lexicon. “The acceptance of the NDA filing moves us closer to providing a meaningful option for people with type 1 diabetes and we look forward to continuing to work closely with the FDA during the review process.”

SGLT2 inhibitors have also been studied in T1D; both drugs are seen as beneficial because of their potential to reduce glycemic variability—the “roller coaster” effect of blood glucose that makes disease management difficult and can bring harmful long-term microvascular effects. The need for patients with T1D to reduce incidents of hypoglycemia is getting more attention than ever, both among drug makers and from those who make devices and develop software.

Sotagliflozin did have 1 issue at EASD: results at Lisbon and in the New England Journal of Medicine showed that patients in the study drug arm reported a DKA rate of 3.0%, compared with 0.6% in the placebo group. Studies of SGLT2 inhibitors in T1D have also observed higher rates of DKA than seen in T2D patients.

A Prescription Drug User Fee Act date is anticipated March 22, 2019, and an application is pending at the European Medicines Agency.