The use of SGLT2 inhibitors has been a game-changer in the treatment of heart failure (HF). Now, another drug class has reached the market that could further alter the HF landscape.
The FDA has expanded the label of Bayer’s Kerendia, a nonsteroidal selective mineralocorticoid receptor antagonist (MRA), to include treatment of patients with two types of heart failure. Kerendia can now be used by HF patients with either preserved ejection fraction (HFpEF) or mildly reduced ejection fraction (HFmrEF).
The U.S. regulator originally approved Kerendia four years ago to reduce the risk of kidney function decline, kidney failure, cardiovascular death, non-fatal heart attacks, and hospitalization for heart failure in adults with chronic kidney disease (CKD) associated with type 2 diabetes.
The new nod allows Kerendia to be given to HF patients who do not have CKD linked to type 2 diabetes.
“Patients with heart failure with mildly reduced EF and heart failure with preserved EF historically have had very limited treatment options,” Alanna Morris-Simon, M.D., Bayer’s senior medical director of U.S. medical affairs, said in an interview. “We’re excited that Kerendia really hopefully will provide a benefit for a very large patient population—larger than we’ve seen based on our current indication.”
HF patients are classified by the ability of their hearts to fill with and pump blood. The measurement tool is left ventricle ejection fraction (LVEF). Those with an LVEF of between 40% and 50% have HFmrEF. Those with an LVEF greater than 50% have HFpEF. With these patients, the heart muscle contracts properly but the ventricles don’t relax.
Kerendia has not been approved for those with an LVEF of less than 40%. These patients have reduced ejection fraction (HFrEF), which means the heart muscle doesn’t contract properly.
While treating HFrEF is relatively straightforward, developing effective medicines for those with HFpEF and HFmrEF has been more difficult. After decades of trial failures, the first drugs to show significant benefits in the more troublesome HF indications were the SGLT2 inhibitors, a group that includes Eli Lilly and Boehringer Ingelheim's Jardiance and AstraZeneca's Farxiga.
“It takes sometimes more time for clinicians to recognize that this is heart failure when they’re dealing with a preserved ejection fraction,” Morris-Simon said. “One of the other reasons why we struggled as a scientific community is we took a lot of the medicines that worked really well in HFrEF—the reduced EF where the heart is weak—and said, ‘OK, let’s try those in HFpEF and see if they work.’ And in fact, they didn’t work.”
Jardiance and Farxiga were originally approved to treat type 2 diabetes and then were later blessed for all types of HF. The added indications helped boost sales of the treatments to $12.4 billion and $7.7 billion, respectively, in 2024, according to Drug Discovery & Development.
As for Bayer, the company is now projecting peak annual sales of Kerendia to reach $3 billion.
As an MRA, Kerendia works as a diuretic, decreasing sodium reabsorption in the kidneys, which triggers increased water excretion and leads to lower blood pressure and a reduction in fluid around the heart.
“When you have heart failure there are different hormones that circulate in your blood that kind of mess up the way that your heart and your kidney talk to each other,” Morris-Simon said. “A drug like Kerendia enables the heart and the kidneys to talk to each other in a much more efficient way by blocking one of those bad hormones.”
Paving the way for Kerendia’s expansion was the FINEARTS-HF phase 3 trial, in which patients received the treatment or placebo on top of standard of care therapy. Kerendia showed a 16% reduction in the risk of cardiovascular death or an HF event compared with placebo. The results were comparable to risk reductions seen in the trials that led to label expansions for Jardiance and Farxiga.
The results in the FINEARTS-HF study were consistent across all prespecified subgroups. It was particularly noteworthy that patients at baseline using an SGLT2 inhibitor—the only treatment option with a strong guideline recommendation in this population—saw the same primary outcome results as those not on one.