Astrazeneca thinks it has found a new standard of care for chronic kidney disease in the shape of its diabetes drug Farxiga. And the drug appears to perform just as well, if not better, in patients without type 2 diabetes than in those with the condition.
Impressive results from the Dapa-CKD trial, presented at the European Society of Cardiology congress yesterday, should give Astra a shot at a market comprising 700 million patients. But, with many early-stage CKD patients not showing symptoms, finding them all could be tricky.
Dapa-CKD, conducted in diabetic and non-diabetic patients with CKD, had been known to be a hit since it was stopped for “overwhelming efficacy” in March (Farxiga could tie a fourth string to its bow, March 30, 2020).
The ESC heard yesterday that the study had found a 39% reduction in its primary endpoint, a composite of worsening renal function or renal or cardiovascular death, with Farxiga versus placebo. Patients taking the SGLT2 inhibitor also had a 31% relative reduction in all-cause death.
Any concerns that the result might have been driven by patients with diabetes turned out to be unfounded. Indeed, the data look better in non-diabetic patients.
During a press briefing on Friday one of the lead investigators, Professor Hiddo Heerspink of the University of Groningen, said there was a 50% reduction in the primary endpoint in the non-diabetic subgroup, versus a 36% reduction in the diabetic cohort. The difference between the groups was not statistically significant, however, he added.
Astra now plans to file Farxiga for CKD within the next few months, the group’s head of biopharmaceuticals R&D, Sir Mene Pangalos, said during the press briefing.
Approval looks likely, but Astra might have trouble getting the drug to patients, particularly those with earlier-stage kidney disease. Professor David Wheeler of University College London, another of Dapa-CKD’s lead investigators, noted that a lot of patients reached an advanced stage of kidney disease without a diagnosis, as they often did not suffer from symptoms early on.
However, he believes that this could be a chicken-and-egg situation: “I think, now we’ve got a treatment that slows the progression of kidney disease, doctors will look harder for these patients.”
Sir Mene added: “From our perspective, the opportunity is 700 million patients. We want to get as many of them diagnosed as possible as early as possible.”
Even if Astra is successful in expanding this market, it could end up doing the legwork for its rivals Lilly and Boehringer Ingelheim, whose own SGLT2 inhibitor Jardiance is in a CKD trial, Empa-Kidney, due to read out in 2022.
The SGLT2s’ impact outside diabetes could be a class effect – something that looks more likely in light of data with Jardiance in heart failure, for which Farxiga was recently approved (ESC 2020 – Jardiance joins Farxiga in showing heart failure benefit, August 29, 2020).
Farxiga’s mechanism of action in CKD is not fully understood, but its most important effect could be reducing pressure in the glomeruli of the kidneys, thereby protecting them from damage, Professors Wheeler and Heerspink speculated.