ESC 2021: Lexicon aims to make its heart failure case with sotagliflozin, a dual SGLT1 and SGLT2 inhibitor

While much of the attention at the European Society of Cardiology (ESC) is expected to center on forthcoming heart failure data for Eli Lilly and Boehringer Ingelheim’s Jardiance, Lexicon Pharmaceuticals thinks it has a winner in the dual SGLT1 and SGLT2 inhibitor sotagliflozin.

The drug, which scored a 2019 approval in Europe to treat Type 1 diabetes alongside insulin, is gunning for larger use in Type 2 diabetes patients with heart failure. This week at ESC, Lexicon will get a chance to present its case to experts in the field, including by presenting new analyses on the med's higher dose.

Specifically, Lexicon and investigators are touting analyses from two phase 3 studies of the med. In one, dubbed SOLOIST, investigators tested the drug against standard of care in 1,222 Type 2 diabetes patients who had recently been hospitalized with worsening heart failure.

In the trial, the drug posted a 33% absolute risk reduction on an endpoint that combined cardiovascular death and hospitalizations or urgent office visits for heart failure. Investigators noticed the benefits within one month of treatment, and the results were consistent among heart failure patients with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF), Lexicon said.

In both conditions, patients' hearts don't pump enough blood. In HFrEF, the heart muscle doesn't contract properly, while in HFpEF, the muscle contracts appropriately but the ventricles do not relax.

RELATED: Lilly, Boehringer Ingelheim's Jardiance scores heart failure FDA nod, and an even bigger win could come later this year

In another sotagliflozin study called SCORED, researchers tested the drug against standard of care in certain patients with Type 2 diabetes, chronic kidney disease and cardio risks. The trial enrolled 10,584 patients. 

Sotagliflozin posted a 26% risk reduction on the same composite endpoint, and investigators saw benefits within three months.

Lexicon and investigators had previously released the SOLOIST and SCORED results, but in new analyses presented at ESC, they found the drug's higher dose, 400 mg, is associated with a more pronounced risk reduction and no new safety concerns.

This year's ESC meeting comes just after Eli Lilly and Boehringer Ingelheim’s SGLT2 inhibitor Jardiance scored an FDA approval to treat HFrEF patients regardless of whether they have diabetes. The partners are presenting data in another set of patients, those with pEF, later this week.

In an interview, Lexicon’s chief medical officer Craig Granowitz, M.D., Ph.D., called the 33% absolute risk reduction in the SOLOIST trial “pretty remarkable.” When starting patients on the treatment before discharge from the hospital, “you see an early, very large benefit,” he added.

“We believe the results are going to be enduring no matter what Lilly shows,” Granowitz said, referencing the forthcoming Jardiance data.

With the results, Lexicon is gearing up to submit an FDA filing later this year in patients with Type 2 diabetes and heart failure, Granowitz said.

RELATED: Sanofi dumps Zynquista collab following phase 3 failures, but Lexicon claps back 

Meanwhile, Lexicon’s drug is already approved in Europe as Zynquista to help treat patients with Type 1 diabetes, but the company hasn’t yet launched there. In 2019, the FDA turned away the med for that use.

Lexicon was previously collaborating with Sanofi on the drug, but the partners parted ways. In a 2019 settlement, Sanofi paid Lexicon $260 million and returned full rights to the drug.