SAN DIEGO—Boehringer Ingelheim and Eli Lilly still don’t know what’s responsible for the dramatic reduction in cardiovascular death risk that Jardiance (empagliflozin) posted in the companies’ outcomes trial. But they know what isn’t.
In a new analysis of data from that trial, EMPA-REG Outcomes, Jardiance reduced the risks of cardiovascular death, all-cause mortality and hospitalizations from heart failure to the same extent even when results were adjusted to control for blood pressure, LDL cholesterol and HbA1c—a key measure of blood glucose levels.
The companies unveiled the analysis in a Saturday presentation at the American Diabetes Association annual meeting.
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“It’s quite clear that the results that we see” from the drugmakers’ Empa-Reg Outcome study—including the 38% reduction in the risk of cardiovascular death—“really is not explained through these classical risk factors we have all been aware of for some decades now,” Thomas Seck, Boehringer’s VP of clinical development and medical affairs for its primary care unit, said in an interview.
It’s good news for BI and Lilly, as it signifies that doctors need to prescribe Jardiance if they want to see the type of results that came out of the study. The drug is now officially FDA-approved to reduce the risk of cardiovascular death.
“Just by managing blood pressure better, just by managing HbA1c better and lipids better—all good things, they should continue to do so—but that will not give the same effect that you see with Empa-Reg,” Seck said.
But it leaves one big, burning question: What is it about the med that’s helping patients’ hearts?
It’s a frequent discussion topic at this year’s ADA conference, Seck said, and it’s been stirring up buzz ever since the companies rolled out the Empa-Reg results in September 2015. And while various theories are floating around as to what’s responsible—hemodynamic effects, effects on the kidney that could be related to effects on the heart, metabolic effects—there’s no “definitive” explanation.
“There are different trains of thought, and all of them might be true,” Seck said. “There’s … no evidence of what the mechanism is at this point.”
The good news, for those wanting answers? Lilly and BI want them, too—and they’re shelling out to get them faster. The company has committed a “substantial amount of money” to “really elucidate” the mechanism of action, in part by investing in investigator-initiated studies coming from “academic leaders in their area that believe they can, with further experiments, clarify what the mechanism is,” Seck said.
“It’s just the beginning,” he added. “I think we will learn a lot over the next 12 to 18 months around mechanism and what empagliflozin does that mediates a 38% reduction in cardiovascular death.”
Meanwhile, the companies are looking at Jardiance in heart failure with two studies that kicked off in mid-March. Those outcomes trials, which involve more than 7,000 patients combined, enrolled heart failure patients of all stripes, “independent of their cardiometabolic status,” Seck said.