FDA says no to Lilly, Boehringer’s Jardiance in type 1 diabetes

The US Food and Drug Administration (FDA) has formally rejected Eli Lilly and Boehringer Ingelheim’s bid to extend the use of their SGLT2 inhibitor Jardiance into type 1 diabetes.

The companies confirmed they had received a complete response letter from the US regulator turning down the marketing application, several months after an advisory committee voted 14-2 against approval.

Jardiance (empagliflozin) is already approved to treat type 2 diabetes, but Lilly and Boehringer had been hoping to expand the number if patients eligible for treatment with the drug by making it available as an add-on to insulin in type 1 patients who struggle to control blood sugar using insulin alone.

The advisory committee said it were concerned about Jardiance’s safety in this setting, and specifically the risk of diabetic ketoacidosis (DKA), a side effect that in severe cases can lead to kidney damage, respiratory failure and death.

While the decision was widely anticipated, its still a blow to the two companies as they try to protect Jardiance’s position in type 2 diabetes in the face of competition from AstraZeneca’s Farxiga/Forxiga (dapagliflozin) and Johnson & Johnson’s Invokana (canagliflozin).

There are around 40,000 new type 1 diabetics diagnosed in the US every year, and at the moment no SGLT2 inhibitors have been approved for adjunctive use with insulin.

Last July the FDA also turned down AstraZeneca’s filing for Farxiga in type 1 diabetes, although the drug has been approved in this indication in Europe and Japan. It also turned down Lexicon Pharma and Sanofi’s SGLT2 inhibitor Zynquista (sotagliflozin) for this use in December, once again despite an earlier approval in Europe.

Lilly and Boehringer submitted trial data from the EASE trial showing that in combination with insulin Jardiance provided a statistically significant reduction in haemoglobin A1C – a marker for glucose control – compared to insulin plus placebo.

“The challenges of managing blood sugar levels for those with type 1 diabetes, and the desire for new treatment options, reveal important unmet needs in the diabetes community,” said Boehringer’s vice president of clinical development medical affairs for cardio-metabolism and respiratory medicine Mohamed Eid.

“We remain committed to the continued study of therapies that may improve outcomes for adults with cardiorenal metabolic conditions, including diabetes,” he added.