Lexicon Pharmaceuticals ($LXRX) was up a bit in early trading on positive Phase II data for its sotagliflozin to treat diabetes. The company said the results confirmed its ongoing Phase III strategy; it reported a first set of top-line Phase III data last month, with another set due in December.
The first-in-class, oral diabetes candidate is being developed under an up to $1.7 billion deal with Sanofi ($SNY). Lexicon got $300 million upfront under the November 2015 deal. Sanofi is slated to pay Lexicon up to $430 million in development and regulatory milestones with an additional up to $990 million in sales milestones.
Lexicon is responsible for Type 1 diabetes clinical development of sotagliflozin, but Sanofi is responsible for Type 2 diabetes development. If Lexicon exercises its co-promotion option, it will pay 40% of commercialization costs in Type 1 diabetes. In Type 2 diabetes, Lexicon will kick in up to $100 million over the next three years for development. Sanofi is slated to book sales worldwide in all indications.
"The inTandem4 Phase 2 dose-ranging study represents the first of three clinical trials of sotagliflozin that we expect to read out in this quarter, including the top-line results from our second pivotal Phase 3 clinical trial," said Lexicon EVP and CMO Dr. Pablo Lapuerta in a statement.
Data for the dual SGLT1 and SGLT2 inhibitor in this inTandem4 Phase II trial found that both doses in the ongoing Phase III program, 200 mg and 400 mg once daily, had significant reductions in A1C relative to placebo. The mean A1C reductions from baseline were 0.60%, 0.84% and 0.73% for the 75-mg, 200-mg and 400-mg doses, respectively, after 12 weeks of treatment. The mean placebo reduction was 0.35%.
The FDA has guided to a clinically meaningful change in A1C being 0.3% or greater for diabetes drug development.
The inTandem4 trial included 141 Type 1 diabetes patients in the U.S. who are on an insulin pump or multiple daily insulin injections with an A1C level of between 7% and 10%. It included, ahead of randomization, a two-week period in which patients received placebo and insulin. Then they were randomized to the three doses of sotagliflozin or placebo. Mean baseline A1C was 7.95% to 8.07% across the four study arms.
Lapuerta added: "We continue to be very encouraged about the potential benefits that sotagliflozin may bring to people with Type 1 diabetes, especially given that we saw significant glycemic control benefits coupled with favorable results on important safety parameters in this trial. In addition, this study provided the first demonstration in the setting of Type 1 diabetes of some of the important characteristics of sotagliflozin's differentiated dual SGLT1 and SGLT2 mechanism of action."
Sotagliflozin's dual mechanism of action is intended to offer inhibition of SGLT1 in the gastrointestinal (GI) tract and SGLT2 in the kidney. The candidate offered dose-related reductions in both postprandial glucose and in urinary glucose excretion, with higher doses reducing the former and increasing the latter with greater efficacy than the low dose or placebo.
The Phase III program for sotagliflozin includes inTandem1, which is on a background of optimized insulin and reported top-line results last month; inTandem2 with top-line data anticipated in December; and inTandem3, a global 1,400-patient study of 400 mg once daily versus placebo on insulin background therapy but without insulin optimization prior to randomization. Sanofi also expects to start Phase III testing of sotagliflozin in Type 2 diabetes this year.