Eli Lilly and Boehringer Ingelheim's Jardiance has been on a tear recently with an FDA fast track in heart failure and a key trial win in kidney disease. But when it comes to treating Type 1 diabetes, the SGLT2 med didn't pass muster in a key FDA panel vote.
An FDA advisory committee voted 14-2 Wednesday against recommending a 2.5 milligram dose of empagliflozin––Jardiance's generic name––on top of insulin to reduce the risk of diabetic ketoacidosis in Type 1 diabetes patients. Boehringer said in a release that a separate brand name had been proposed for empagliflozin in that indication.
Although the committee's vote isn't the last say on Lilly and Boehringer's Type 1 hopes, the FDA often follows its advisers' recommendations. That's a big knock for the drugmakers, with around 40,000 new patients diagnosed with Type 1 diabetes each year in the U.S., Boehringer said.
The committee reviewed data from the phase 3 Ease trial, which showed empagliflozin and insulin provided a significant reduction in A1C versus a placebo-insulin pair in adults with Type 1 diabetes, Boehringer said. The drug also hit its secondary endpoints of reducing patients' weight and systolic blood pressure with a comparable safety profile to the placebo control.
In a briefing for the committee, Lisa Yanoff, acting director of the FDA's endocrinologic and metabolic drugs committee, pointed out that Lilly and Boehringer's submission relied on a single phase 3 trial with a relatively small patient pool and short duration. Despite the drugmakers' finding that empagliflozin did not show a significantly higher rate of diabetic ketoacidosis over placebo, Yanoff said the trial's limitations may have suppressed the SGLT2 class' observed rate of higher diabetic ketoacidosis occurrence.
"Typically, two adequate and well-controlled studies to establish effectiveness of a product are available, that can also be relied upon on for evaluation of drug risk," Yanoff wrote. "In the current application, only one pivotal phase 3 trial evaluated the 2.5 mg dose."
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With the committee knockdown, it could be back to the drawing board for emplagliflozin's Type 1 hopes. But Lilly and Boehringer can take some solace in the drug's performance in the Type 2 form of the disease.
In September, real-world data pitting Jardiance against GLP-1 diabetes meds showed Lilly and Boehringer's drug pared down the risk of heart failure hospitalizations by 26%.
“We really think that is good for patients because heart failure in diabetes is really very common, and it leads to premature death and lots of costs to health systems,” Jyothis George, BI’s head of medicine for Jardiance, said at the time.
The real-world study backed up Jardiance's fast-track nod from the FDA in June as a treatment for reducing the risks of cardiovascular death and hospitalization for heart failure among chronic heart failure patients. That designation applied to two ongoing studies, dubbed Emperor-Reduced and Emperor-Preserved. Between them, the studies comprised more than 8,500 heart failure patients from a pool that could count up to 6.5 million in the U.S. and 26 million globally, according to Boehringer.
Jardiance set itself apart in the SGLT2 class after its landmark Empa-Reg study from 2015 showed a 14% reduced risk of major CV events in Type 2 diabetes patients and established a new frontier for diabetes meds. The drug went on to win a label update based on those data, clearing its makers to talk up its ability to slash diabetes patients' risk of cardiovascular death.
Since then, other SGLT2s have started to catch up, including AstraZeneca's Farxiga, which scored a potentially game-changing trial win in reducing CV risks in patients with or without Type 2 diabetes.