Sanofi Terminates Zynquista Collaboration with Lexicon Following Mixed Phase 3 Results in Type 2 Diabetes

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Sanofi recently announced the topline results from three Phase III clinical trials of Zynquista (sotagliflozin) for the treatment of adult patients with type 2 diabetes, as part of its Insynchrony clinical program:

——SOTA-MET Study:Conducted in patients with type 2 diabetes whose blood glucose was not adequately controlled with metformin, the results showed that at Week 26 of treatment, the Zynquista (400 mg) group achieved a statistically significant reduction in HbA1c compared with the placebo group.

——SOTA-CKD3 Study:Conducted in patients with type 2 diabetes and moderate (stage 3) chronic kidney disease (CKD), the results showed that at week 26 of treatment, Zynquista (400 mg) achieved a statistically significant reduction in HbA1c compared with the placebo group in both the overall patient population and the subgroup of patients with an estimated glomerular filtration rate (eGFR) of 45 to <60 mL/min/1.73 m² (stage 3A). However, in the subgroup of patients with an eGFR of 30 to <45 mL/min/1.73 m² (stage 3B), although Zynquista (400 mg) demonstrated improvement in lowering HbA1c, the data did not reach statistical significance.

——SOTA-CKD4 Study:Conducted in patients with type 2 diabetes and severe (stage 4) chronic kidney disease (CKD), the results showed that at week 26 of treatment, Zynquista (200 mg and 400 mg) demonstrated a clinically meaningful reduction in HbA1c compared with placebo, but did not achieve statistical significance.

In the three studies mentioned above, Zynquista demonstrated good tolerability, with no imbalances or new safety signals identified. Detailed data from these studies will be presented at upcoming medical conferences.

In light of the primary endpoint results for glycemic control (HbA1c) in the SOTA-CKD3 and SOTA-CKD4 studies, Sanofi has issued a notice to its partner Lexicon to terminate the collaboration between the two parties on the development, manufacturing, and commercialization of Zynquista across all ongoing global type 1 and type 2 diabetes programs.

The ongoing Phase III clinical trials will continue without immediate changes. Sanofi stated that it is willing to collaborate with Lexicon to ensure a smooth transition of the studies.

However, Lexicon deemed the notice invalid and asserted that Sanofi had breached the contract. This is because the Collaboration and License Agreement stipulates that, even upon effective termination of the alliance, Sanofi remains contractually obligated to transfer the rights to Zynquista and continue funding ongoing clinical trials for a specified period post-termination as outlined in the agreement.

Lonnel Coats, President and Chief Executive Officer of Lexicon Pharmaceuticals, stated, “While we are disappointed by Sanofi’s position, we remain confident in the robust data currently observed in our type 2 diabetes program and are optimistic about the continued success of this pivotal Phase III program, which we expect to complete in the coming months. In the event of an effective termination of the alliance with Sanofi, we also look forward to regaining full rights to Zynquista for the treatment of patients with type 1 diabetes in the United States, as well as in other regions worldwide, particularly including the European Union, where Zynquista has already received regulatory approval for the treatment of type 1 diabetes.”

The active pharmaceutical ingredient of Zynquista is sotagliflozin, a dual SGLT-1/SGLT-2 inhibitor, which is being developed for the treatment of type 1 and type 2 diabetes.

SGLT-1 and SGLT-2

Sotagliflozin was developed by Lexicon. In November 2015, Sanofi reached a $1.7 billion licensing agreement with Lexicon, obtaining exclusive global rights to the drug except in Japan.

From a regulatory perspective, Zynquista received approval from the European Union in late April this year as an adjunct to insulin for adult patients with type 1 diabetes who have a body mass index (BMI) ≥27 kg/m² and fail to achieve adequate glycemic control despite optimal insulin therapy. Zynquista is administered orally at once-daily doses of 200 mg and 400 mg. In the United States, the FDA rejected Zynquista in March this year due to an increased risk of diabetic ketoacidosis (DKA) when Zynquista was used in combination with insulin compared with insulin alone.

In addition to type 1 diabetes, Zynquista is currently being developed for the treatment of type 2 diabetes. The development program for type 2 diabetes comprises 11 studies, including two studies in patients with type 2 diabetes and renal impairment, as well as two large cardiovascular outcome trials.

Competition in the type 1 diabetes treatment landscape is intensifying. Currently, three SGLT inhibitors have been approved in Japan and the European Union, but none have yet received approval in the U.S. market. In addition to Zynquista, Astellas’ Suglat was approved in Japan in December 2018 for the treatment of type 1 diabetes. In March this year, AstraZeneca’s Forxiga gained approval in the EU and Japan for treating type 1 diabetes; however, the FDA rejected the drug in the U.S. earlier this month due to concerns over the risk of diabetic ketoacidosis (DKA). Furthermore, Eli Lilly and Boehringer Ingelheim are conducting Phase III clinical development of the SGLT2 inhibitor Jardiance for type 1 diabetes, while Johnson & Johnson is also developing a new indication for its SGLT2 inhibitor Invokana in type 1 diabetes.

Reference Source: Lexicon Pharmaceuticals Provides Preliminary Update for Zynquista (Sotagliflozin) Type 2 Diabetes Phase 3 Program

Original Title:Phase 3 Clinical Results of Zynquista for Type 2 Diabetes Released; Sanofi and Lexicon “Break Up”!