Citing lack of efficacy evidence, the FDA rejected Cytokinetics’ heart failure hopeful omecamtiv mecarbil in a decision announced Tuesday evening.
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Citing lack of efficacy evidence, the FDA rejected Cytokinetics’ heart failure hopeful omecamtiv mecarbil in decision announced Tuesday evening.
In its Complete Response Letter, the regulator said a single Phase III trial was not enough to establish clinical benefit for Cytokinetics’ candidate in adult patients with chronic heart failure with reduced ejection fraction (HFrEF).
The FDA requested data from another trial showing that the candidate’s benefits outweigh its risks.
Cytokinetics, however, “has no plans to conduct an additional clinical trial of omecamtiv mecarbil,” according to Tuesday’s press release.
The company will seek a meeting with the regulator “to understand FDA’s views regarding the CRL” and determine the best next steps for the candidate.
Cytokinetics’ shares were down 8% in post-market trading Tuesday following the CRL.
Omecamtiv mecarbil is a small molecule activator of cardiac myosin and works by increasing the active actin-myosin cross bridges during the cardiac cycle. In turn, the candidate improves the weak contractility typical of HFrEF.
Cytokinetics supported the NDA with data from the Phase III GALACTIC-HF trial. Compared with placebo, omecamtiv mecarbil reduced the rate of the primary outcome – a composite between cardiovascular death and time to first heart failure event – by a significant 8%. The candidate was even more effective in patients with low baseline left ventricular ejection fraction.
With more than 8,250 patients, GALACTIC-HF is one of the largest trials ever conducted in heart failure.
In December 2022, the FDA’s Cardiovascular and Renal Drugs Advisory Committee voted 8-3 against omecamtiv mecarbil. The panel of independent experts said results from a single trial, with what they called a small treatment effect, were not enough to support the candidate’s approval.
Cytokinetics Shifts Gears from Activation to Inhibition
Following the regulatory stumble with its myosin activator, Cytokinetics indicated it will channel its resources into its investigational cardiac myosin inhibitor aficamten, currently in a Phase III trial for hypertrophic cardiomyopathy (HCM).
By blocking myosin’s action, aficamten prevents hypercontractility and muscle thickening in the heart associated with HCM. The trial, dubbed SEQUOIA-HCM, is a randomized, placebo-controlled and double-blinded study assessing the efficacy and safety of aficamten. It kicked off in February 2022 and as of November 2022, was undergoing site activation.
In the Phase II REDWOOD-HCM study, aficamten significantly reduced average resting left ventricular outflow tract pressure gradient relative to placebo. Based on these results, the FDA granted the candidate Breakthrough Therapy designation in December 2021.
In Tuesday’s announcement, Robert Blum, president and CEO, Cytokinetics, said the company expects results from SEQUOIA-HCM and will have two more Phase III trials later in 2023.
