Persistent Lexicon still working to get an audience with FDA on Type 1 diabetes prospect

Lexicon Pharmaceuticals won't take no for an answer.

The Texas pharma—convinced of the value of its diabetes candidate sotagliflozin—has clapped back at its latest rejection from the FDA, asking to be heard in its attempt to gain approval for the drug in Type 1 diabetes.

Sotagliflozin, which won approval in Europe for Type 1 diabetes in 2019, was first rejected in the U.S. that same year over safety concerns, prompting Sanofi to bail on a partnership deal with Lexicon. The money gained in that divorce has helped Lexicon continue its pursuit.

While the agency has ruled more than once that a regimen of sotagliflozin plus insulin can increase the risk of potentially fatal diabetic ketoacidosis (DKA), Lexicon maintains that the risk can be managed and points to the unmet need in the treatment of Type 1 disease.

“Healthcare providers and T1DM patients are well aware of the recommended steps to avoid, identify, and treat DKA,” Lexicon wrote in a filing. “These measures have been established through evidence-based treatment guidelines.”

The company is requesting that the agency allow resubmission of its new drug application for sotagliflozin, along with a proposed Risk Evaluation and Mitigation Strategy. The program is extended to some drugs to ensure they are used in a way that confirms their benefits outweighs their risks.

In an attempt to enhance its claim, Lexicon also points to the widespread use of SGLT2 inhibitors approved for Type 2 diabetes that also carry a risk of DKA.

“Treating similarly situated products differently, without adequate and reasoned explanation, is arbitrary and capricious,” Lexicon wrote.

The effectiveness of sotagliflozin has been proven in three phase 3 studies, “all of which achieved their pre-specified primary endpoints and demonstrated a statistically significant and clinically meaningful improvement in glycosylated hemoglobin (HbA1c) levels,” according to the company.

Lexicon also pointed to secondary benefits including reductions in body weight, blood pressure and glycemic variability—all achieved without increases in hypoglycemic events.

But the FDA disputes the benefits as well. In its complete response letter to Lexicon in 2019, the agency wrote that the “modest clinical benefits” of sotagliflozin did not justify the risks.

Since then, the company has come back to the regulator with appeals, suggested tweaks to mitigate risks and additional data. Each time, the answer from the FDA has been the same.

In July of this year, the FDA’s Center for Drug Evaluation and Research presented a proposed order to deny Lexicon’s latest hearing request, saying the company had not provided enough evidence to justify one. That decision prompted Lexicon’s 53-page response.

Lexicon also is seeking an approval for sotagliflozin to reduce severe cardiovascular risks in Type 2 diabetes patients. Early this year, the company pulled its application to fix a "technical issue" it identified in the filing. 

Meanwhile, amid Lexicon's efforts, a new Type 1 diabetes drug has hit the scene. Two weeks ago, Provention Bio's Tzield won an FDA approval to delay progression of the disease, culminating a 36-year journey for the medicine.