Generally speaking, the application of SGLT2 inhibitors has revolutionized the management of heart failure (HF). A new class of pharmaceuticals has now emerged that may significantly impact the heart failure landscape.
The FDA has broadened the indication for Kerendia, Bayer’s nonsteroidal selective mineralocorticoid receptor antagonist (MRA), to cover the medical care of individuals with two forms of heart failure. Kerendia is now applicable for heart failure individuals with either preserved ejection fraction (HFpEF) or mildly reduced ejection fraction (HFmrEF).
The U.S. FDA first authorized Kerendia four years before to mitigate the risk of renal function deterioration, kidney failure, cardiac deaths, non-fatal strokes, and hospitalization due to heart failure in people with chronic kidney disease (CKD) linked to type 2 diabetes.
The recent approval permits Kerendia to be administered to heart failure patients without chronic kidney disease associated with type 2 diabetes.
Alanna Morris-Simon, M.D., Bayer’s senior medical director, explained in an interview that individuals with heart failure with mildly reduced or preserved ejection fraction have traditionally faced a lack of effective treatment choices. She expressed optimism that Kerendia could offer meaningful benefits to a significantly broader group of patients than those currently covered under its existing indication.
Heart failure patients are categorized based on their hearts’ capacity for filling with and pumping blood. The metric used is the left ventricular ejection fraction (LVEF). Individuals with an LVEF ranging from 40% to 50% are classified as having HFmrEF. Those with an LVEF over 50% are diagnosed with HFpEF. In these individuals, the cardiac muscle contracts appropriately; however, the ventricles fail to relax.
Kerendia has not received approval for individuals with an LVEF below 40%. These individuals have decreased ejection fraction (HFrEF), indicating that their heart muscle fails to contract adequately.
Treating HFrEF is rather simple; however formulating effective medications for people with HFpEF and HFmrEF has proven to be more challenging. Following decades of unsuccessful trials, the first medications demonstrating substantial advantages in the more challenging heart failure indications were the SGLT2 inhibitors, which include Eli Lilly’s Jardiance and Farxiga from AstraZeneca.
Morris-Simon pointed out that clinicians often need more time to identify heart failure in patients with preserved ejection fraction. She explained that one of the challenges the scientific community has faced is the assumption that treatments effective for heart failure with reduced ejection fraction—where the heart muscle is weakened—would also be effective for heart failure with preserved ejection fraction. However, she noted that those therapies ultimately proved ineffective in that context.
The FINEARTS-HF phase 3 study facilitated Kerendia’s expansion, whereby patients were given either the drug or a placebo in conjunction with standard care therapy. Kerendia showed a 16% decrease in the risk of cardiovascular mortality or a heart failure episode versus the placebo. The outcomes were similar to the risk decreases seen in the studies that resulted in label extensions for Jardiance and Farxiga.
The outcomes of the FINEARTS-HF trial were uniform across all subgroups. It is especially significant because individuals at baseline with an SGLT2 inhibitor – the only therapy choice with solid guideline endorsement in this demographic – exhibited identical main outcome outcomes as those not receiving it.
