A U.S. FDA advisory committee voted against recommending Cytokinetics' heart failure med, noting safety and efficacy concerns.
The Cardiovascular and Renal Drugs Advisory Committee (CRDAC) voted 8 to 3 that the benefits of omecamtiv mecarbil do not outweigh its risks for the treatment of heart failure with reduced ejection fraction (HFrEF).
Based on lukewarm single trial results, FDA reviewers had raised concerns about the drug's safety, especially at higher doses, in briefing documents released in advance of the meeting. The panel agreed, also suggesting that Cytokinetics gather additional data on the drug's ability to reduce the risk of heart-failure related death.
The AdComm's vote was based on the results from the phase 3 GALACTIC-HF clinical trial that enrolled 8,256 patients with HFrEF who were at risk of hospitalization and death, despite being well treated on standard-of-care therapy. The trial began as a collaboration with Amgen, who bailed on the deal back in NOv. 2020 after seeing trial results. While the trial demonstrated that treatment with omecamtiv mecarbil reduced risk of the primary composite endpoint of cardiovascular death or heart failure events by 8% compared to placebo, Amgen had set a bar at 15% risk reduction as being clinically meaningful. Moreover, no reduction in the secondary endpoint of time to cardiovascular death was observed.
Omecamtiv mecarbil is an investigational, selective, small molecule cardiac myosin activator. If approved by the FDA, it will be the first therapy indicated for HFrEF that directly targets the heart's pumping function.
Facing a PDUFA date of Feb. 28, 2023, the FDA will now have to decide whether to follow the panel's advice. California-based Cytokinetics has not given up.
“We continue to believe omecamtiv mecarbil can be a valuable add-on therapy for patients with worsening heart failure who remain at high risk for heart failure events and hospitalization despite treatment with available guideline-directed medical therapy. We plan to engage constructively with FDA as it completes its review of the application for omecamtiv mecarbil,” said Robert Blum, Cytokinetics CEO.
