FDA advisers divided on Sanofi’s oral type 1 diabetes drug

The future of Sanofi and Lexicon’s oral diabetes drug Zynquista hangs in the balance after an FDA advisory committee was split on whether the drug would benefit patients.

The Endocrinologic and Metabolic Drugs Advisory Committee voted eight to eight on the question of whether the overall benefits of Zynquista (sotagliflozin) outweighed the risks enough to support approval.

While the FDA is not required to follow the committee's vote, the agency considers the committee's recommendations when making its decision, which is anticipated by March 22, 2019.

Zynquista is an investigational oral dual SGLT1 and SGLT2 inhibitor under review as an adjunct to insulin for the treatment of adults with type 1 diabetes (T1D).  The drug has the potential to be only the second non-insulin product approved for T1D in the US, and the first oral antidiabetic drug approved together with insulin to improve blood sugar control. Previously, consensus forecasts from EvaluatePharma suggested Zynquista could have sales of $1.16 billion by 2022.

But the drug has been shown to come with a higher risk of patients developing diabetic ketoacidosis (DKA) – which can lead to acute kidney injury, respiratory failure, and death – compared to using insulin alone, and this was despite trial participants being given instructions on how to avoid DKA. This is the key factor that has made the drug controversial among the Committee, many of whom were concerned that patients using the drug in the real world without the intense supervision of a clinical trial would have an even greater risk of DKA. Some committee members said that their fears could be allayed if a proposed risk evaluation and mitigation strategy is tested first.

Lexicon’s executive vice president and chief medical officer, Pablo Lapuerta, said that diabetic ketoacidosis is “an inherent risk of type 1 diabetes” and that it can potentially be addressed with proper education and monitoring.

“In clinical trials, when used in combination with insulin therapy, Zynquista significantly improved glycemic control without increasing hypoglycemia,” he added. “These results could not be achieved with insulin alone.”

Sanofi’s Rachele Berria, global vice president and head of diabetes medical affairs, said that the company “believes in the overall benefit-risk profile of Zynquista for adults with type 1 diabetes” and that both Sanofi and Lexicon would continue to work with the FDA through its review process.

Sanofi also submitted a regulatory application to the EMA in March 2018. An EMA approval decision is expected in the first half of 2019.