#ACC21: AstraZeneca's Farxiga missed big on Covid-19 study, but it's taking SGLT2 safety data as a silver lining
AstraZeneca hasn’t seen many setbacks in recent months for SGLT2 inhibitor Farxiga, which broke ground in heart failure and kidney disease regardless of diabetes diagnosis. But the British drugmaker had to admit defeat in taking Farxiga into Covid-19. However, follow-up results add a bit of a silver lining to that trial’s safety data.
Of hospitalized Covid-19 patients dosed with AstraZeneca’s Farxiga, 11.2% experienced an organ failure or died after 30 days of therapy compared with 13.8% of those given placebo, according to follow-up data from the DARE-19 study revealed Sunday at the virtual American College of Cardiology meeting.
It’s a bad miss in a high-risk population for Farxiga, an SGLT2 inhibitor that recently won approvals in heart failure and kidney disease regardless of a diabetes diagnosis. AstraZeneca released topline data from that Phase III study back in April, apparently putting an end to Farxiga’s quest against Covid-19.
Researchers pointed out that on all organ failure events — including lung, heart or kidney — or death, Farxiga posted results that were “directionally favorable” over placebo but not at a significant level. Mikhail Kosiborod, the study’s lead researcher, said better clinical outcomes in the study’s 1,250 patients tied to improving standard of care between April 2020 and January.
“Our study generates a hypothesis that (Farxiga) may offer organ protection in acutely ill patients who are hospitalized with COVID-19, but we were not able to prove this beyond a reasonable doubt because patient outcomes rapidly improved during the study period, making it much harder to accrue enough events and reach statistical certainty,” Kosiborod said in a statement.
Despite the fail, what AstraZeneca is taking away from the results is that its SGLT2 showed a comparable safety profile to placebo, adding more information to clinical guidance for high-risk patients who are also taking an SGLT2 during Covid-19 therapy.
Patients on Farxiga posted numerically fewer serious side effects than placebo in DARE-19 with two non-severe cases of diabetic ketoacidosis observed, both in the Farxiga arm and in patients with prior history of type 2 diabetes.
“Our study opens the door to asking additional questions,” Kosiborod said. “The idea for DARE-19 was quite unorthodox when we started — everyone was concentrating on antivirals and anti-inflammatory drugs, so it is fascinating to hypothesize that SGLT2 inhibitors may provide organ protection in acute illness. This should inform future clinical science and hopefully lead to further investigations.”