Lexicon Pharmaceuticals announced positive top-line results from its Phase 3 inTandem3 study of sotagliflozin, an investigational dual SGLT1 and SGLT2 inhibitor, for the treatment of patients with type 1 diabetes on any background insulin therapy. The study met its primary endpoint, demonstrating the superiority of sotagliflozin 400 mg compared to placebo in the proportion of patients with A1C <7.0% at Week 24 and no episode of severe hypoglycemia and no episode of diabetic ketoacidosis (DKA) after randomization.
Sotagliflozin demonstrated a generally well tolerated safety profile during a 24-week treatment period, with rates of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and discontinuations due to AEs that were consistent with rates seen in two prior pivotal Phase 3 studies, inTandem1 and inTandem2, including a similar rate of severe hypoglycemia for the sotagliflozin arm compared to placebo during the 24-week treatment period (2.4% for placebo compared to 3.0% for sotagliflozin 400 mg) and a slightly higher rate of DKA during the 24-week treatment period for sotagliflozin 400 mg (3.0%) than placebo (0.6%).
A full analysis of the results from inTandem3, including safety data, will be submitted for publication in a peer-reviewed journal.
“The results achieved with sotagliflozin in the inTandem3 study are scientifically and clinically important and significant,” said Satish Garg, M.D., lead investigator of in Tandem3 and Professor of Medicine and Pediatrics, and Director Adult Program at the Barbara Davis Center for Diabetes, University of Colorado Denver and Editor-in-Chief, Diabetes Technology and Therapeutics. “If approved, sotagliflozin may potentially be the first option as an adjunct to insulin to improve glycemic control for patients with type 1 diabetes.”
“These positive results represent an important milestone, further supporting sotagliflozin’s differentiated profile as a novel, oral anti-diabetic agent with potential to benefit people with type 1 diabetes,” said Lonnel Coats, Lexicon’s president and chief executive officer. “Sotagliflozin is the first-ever oral anti-diabetic drug candidate to have achieved success in now three consecutive Phase 3 clinical trials in this population.”
“These compelling results speak to the potential long-term benefits that sotagliflozin may bring to people with type 1 diabetes,” said Jorge Insuasty, senior vice president, head of global development, Sanofi. “There are more than 1 million adults with type 1 diabetes in the United States alone, and the majority of these are not at their A1C goal of 7 percent. The need for diabetes therapies that help adults with type 1 diabetes control their blood sugar with fewer complications is clear, and sotagliflozin added to insulin therapy can potentially help meet that need. We look forward to pursuing regulatory submissions for the treatment of type 1 worldwide and to continuing to study the use of sotagliflozin in adults with type 2 diabetes.”
The Phase 3 study known as inTandem3 was a global, randomized, double-blind, placebo-controlled, parallel-group, multicenter study of 1,402 patients with type 1 diabetes on continuous subcutaneous insulin infusion or multiple daily injection therapy who had an A1C level entering the study between 7.0% and 11.0%. Patients had a confirmed diagnosis of type 1 diabetes and inadequate glycemic control on insulin therapy alone. The study evaluated 400 mg of sotagliflozin taken once daily before the first meal of the day, against placebo. The primary objective of the study was to demonstrate the superiority of sotagliflozin 400 mg versus placebo in the proportion of patients with glycosylated A1C <7.0% at Week 24 and no episode of severe hypoglycemia and no episode of DKA after randomization.
Discovered using Lexicon’s unique approach to gene science, sotagliflozin is a first-in-class, oral dual inhibitor of two proteins responsible for glucose regulation known as sodium-glucose co-transporter types 1 and 2 (SGLT1 and SGLT2). SGLT1 is responsible for glucose absorption in the gastrointestinal tract, and SGLT2 is responsible for glucose reabsorption by the kidney.
Lexicon entered into a collaboration and license agreement with Sanofi in November 2015 under which Lexicon granted Sanofi an exclusive, worldwide (excluding Japan), royalty-bearing right and license to develop, manufacture and commercialize sotagliflozin. Lexicon is responsible for all clinical development activities relating to type 1 diabetes and retains an exclusive option to co-promote and have a significant role, in collaboration with Sanofi, in the commercialization of sotagliflozin for the treatment of type 1 diabetes in the U.S. Sanofi is responsible for all clinical development and commercialization of sotagliflozin for the treatment of type 2 diabetes worldwide (excluding Japan) and is solely responsible for the commercialization of sotagliflozin for the treatment of type 1 diabetes outside the U.S. (excluding Japan).