FDA rejects Cytokinetics’ heart failure drug

The FDA has followed the advice of its expert advisors and rejected Cytokinetics’ cardiac myosin activator omecamtiv mecarbil as a treatment for heart failure, saying the efficacy data for the drug was lacking.

The decision wasn’t a surprise, given that an FDA advisory committee voted against approval for patients with heart failure with reduced ejection fraction (HFrEF) last December, after concluding the drug’s efficacy did not outweigh the drug’s side effects, which include cardiotoxicity, such as myocardial ischaemia.

The filing was based mainly on the results of the GALACTIC-HF study, which met its primary objective of reducing cardiovascular death or heart failure events compared with placebo in HFrEF patients, cutting the combined rate by 8% when given on top of standard-of-care therapy, and by 15% in a subgroup of very ill patients.

In a statement, Cytokinetics said the US regulator had concluded that GALACTIC-HF was not “sufficiently persuasive.”

Last year, Cytokinetics also reported that the METEORIC-HF trial was unable to show an improved performance in exercise capacity between HFrEF patients treated with omecamtiv mecarbil and placebo, although that data was not considered by the advisory committee.

The complete response letter from the FDA makes it more likely that Cytokinetics will shelve omecamtiv mecarbil and turn its attention to aficamten, a cardiac myosin inhibitor in phase 3 for symptomatic hypertrophic cardiomyopathies (HCM), according to analysts.

For now, however, Cytokinetics isn’t ruling out sticking with omecamtiv mecarbil. It said it plans to request a meeting with the FDA in order to understand what additional information may be required to support an approval.

That could be challenging, given that there has been a number of new therapy launches in the HFrEF category since Cytokinetics first started developing omecamtiv mecarbil around 15 years ago, notably Novartis’s Entresto (sacubitril/valsartan) and SGLT2 inhibitors such as AstraZeneca’s Forxiga/Farxiga (dapagliflozin) and Eli Lilly/Boehringer Ingelheim’s Jardiance (empagliflozin).

“We are disappointed with this outcome, especially considering the high unmet need for innovative treatments for patients suffering from worsening heart failure,” commented the biotech’s president and CEO, Robert Blum.

The likelihood now is that Cytokinetics will have to re-align itself around aficamten, currently in the SEQUOIA-HCM pivotal trial which is due to generate results later in 2023, and with two more studies due to start before the end of the year.

Shares in Cytokinetics only dipped slightly after the rejection, perhaps reflecting a sentiment among investors that it would be better to cut its losses and turn its attention to aficamten and avoid a costly bid to try to get the HFrEF programme back on track.