Cytokinetics’ Phase III Data Sets Up Cardiomyopathy Challenge to BMS

Heart ultrasound_iStock, sudok1

Pictured: Ultrasound machine showing a heart scan/iStock, sudok1

Cytokinetics on Monday unveiled primary data from its highly anticipated Phase III SEQUOIA-HCM study, showing that its investigational cardiac myosin blocker aficamten significantly improved exercise capacity in patients with obstructive hypertrophic cardiomyopathy.

At 24 weeks, peak oxygen uptake increased by 1.8-mL/kg/min in patients treated with aficatmen, while placebo counterparts saw zero change in this metric. This effect was statistically significant, according to Cytokinetics, and aficamten’s therapeutic benefits were consistent across different subgroups, including age, sex and background use of beta-blockers.

The drug candidate also met its key secondary endpoints, significantly reducing symptom burden in treated patients versus placebo, as quantified by the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score. At 24 weeks, aficamten substantially lowered the levels of NT-proBNP, an indicator of cardiac wall stress.

In terms of safety, SEQUIOA-HCM found that aficamten was well-tolerated and its adverse event profile was comparable to that of the placebo group. There were no instances of worsening heart failure and none of the patients had to stop treatment due to side effects. Cytokinetics also published these data on Monday in The New England Journal of Medicine.

Fady Malik, executive vice president of R&D at Cytokinetics, in a statement said these data from SEQUIOA-HCM show that “aficamten is associated with statistically significant, rapid and sustained improvements in exercise capacity, symptoms, cardiac function and cardiac biomarkers” in patients with obstructive hypertrophic cardiomyopathy (HCM).

These findings “are strongly supportive of the potential approval of aficamten,” Malik continued, adding that Cytokinetics currently plans to submit regulatory filings for the drug candidate in the U.S. and Europe later this year.

Monday’s readout brings Cytokinetics one step closer to a first approval and a positive ending to what has been a difficult road for the company. In February 2023, the FDA rejected Cytokinetics’s small molecule cardiac myosin activator omecamtiv mecarbil, which it proposed as a treatment for heart failure.

At the time, the FDA said that the Phase III data supporting omecamtiv mecarbil was not enough to establish its clinical benefit and requested another trial. However, Cytokinetics indicated that it had no plans to conduct an additional clinical trial for the candidate and about a month later the biotech announced that it was discontinuing the development of its amyotrophic lateral sclerosis candidate reldesemtiv after disappointing Phase III findings.

If approved, aficamten will compete with Bristol Myers Squibb and its oral drug Camzyos (mavacamten), which was approved in April 2022 for obstructive HCM patients of New York Heart Association Class II to III. Camzyos comes with a boxed warning for heart failure due to systolic dysfunction.

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

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