Aficamten improves HF symptoms, hemodynamics at 10 weeks in obstructive HCM
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Aficamten, a novel selective cardiac myosin inhibitor, was associated with improvements in HF symptoms and hemodynamics at 10 weeks, according to a phase 2 study presented at the Heart Failure Society of America Annual Scientific Meeting.
According to the researchers, treatment with aficamten (Cytokinetics) resulted in no treatment-related serious adverse events and no excess incidence of adverse events compared with placebo in the phase 2 REDWOOD-HCM trial of patients with obstructive hypertrophic cardiomyopathy (HCM).
As Healio previously reported, top-line results from REDWOOD-HCM were released in July.
Aficamten “binds to the myosin head to decrease the number of myosin-actin interactions that are occurring at the sarcomere level,” Martin S. Maron, MD, director of the Hypertrophic Cardiomyopathy Center and Research Institute at Tufts Medical Center, Boston, and principal investigator of the trial, told Healio. “In a disease like hypertrophic cardiomyopathy, there is an excess number of myosin-actin interactions. By decreasing those, you decrease the force of myocardial contractility, which has a number of favorable downstream effects, including lowering or abolishing the outflow gradient, which will make patients feel a lot better by significantly decreasing heart failure symptoms.”
Maron and colleagues randomly assigned 41 patients (mean age, 57 years; approximately 60% women) with symptomatic HCM, left ventricular ejection fraction 60% or more and resting LV outflow tract gradient 50 mm Hg or more (or 30 mm Hg or more if Valsava LV outflow tract gradient was 50 mm Hg or more) to aficamten 5 mg followed by 10 mg followed by 15 mg (cohort 1), aficamten 10 mg followed by 20 mg followed by 30 mg (cohort 2) or placebo.
At 10 weeks, both aficamten cohorts had improved resting LV outflow tract gradient compared with the placebo group (P < .001 for both) and improved Valsava outflow tract gradient (P for cohort 1 vs. placebo < .001; P for cohort 2 vs. placebo < .0001), Maron said during a presentation.
The percentage of responders, defined as resting LV outflow tract gradient less than 30 mm Hg and Valsava LV outflow tract gradient less than 50 mm Hg, at 10 weeks was 93% in cohort 2, 78% in cohort 1 and 8% in the placebo group, he said.
“Aficamten was very successful at obliterating the outflow gradients in the vast majority of patients on the drug,” Maron told Healio. “Gradients were reduced significantly within 2 weeks of initiating the drug.”
LVEF was reduced in both aficamten cohorts vs. placebo during the study period (P < .05 for both), according to the researchers.
The aficamten groups had reduced N-terminal pro-B-type natriuretic peptide levels at 10 weeks compared with the placebo group (P for both cohorts combined vs. placebo = .003), Maron said.
HF symptom response, defined as improvement by at least one NYHA class, at 10 weeks occurred in 64% of cohort 2, 43% of cohort 1 and 31% of the placebo group (P for cohort 2 vs. placebo = .08; P for cohort 1 vs. placebo > .1), he said.
There were two serious adverse events, one in the placebo group and one in the cohort 1 aficamten group, neither of which were related to treatment or resulted in early termination of treatment, he said.
“The next step is that there is strong support for moving forward with a phase 3 clinical trial to further understand the extent of the clinical benefit of this drug in symptomatic obstructive HCM patients,” Maron told Healio.
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Maron M, et al. Late-Breaking Clinical Trials I. Presented at: Heart Failure Society of America Annual Scientific Meeting; Sept. 10-13, 2021; Denver (hybrid meeting).
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