Clinical trial investigating aficamten meets primary endpoint in obstructive hypertrophic cardiomyopathy

Although mortality and hospitalization charges have improved, the standard of life for these residing with hypertrophic cardiomyopathy (HCM) will be compromised with limiting signs comparable to exertional dyspnea and decreased train capability. A serious reason for this in HCM sufferers is left ventricular outflow tract (LVOT) obstruction, which leads to elevated intracardiac pressures.

A medical trial has demonstrated that aficamten enhanced HCM sufferers’ train capability with vital enchancment in peak oxygen uptake (pVO2), enchancment in limiting signs, and reduces in LVOT strain gradients. The analysis was offered at Coronary heart Failure 2024.

“The SEQUOIA-HCM trial demonstrated that aficamten can reliably and safely eradicate LVOT obstruction in sufferers with obstructive HCM utilizing a easy and stepwise dosing routine, and was related to substantial enhancements in clinically related endpoints comparable to train capability and signs,” mentioned principal investigator Professor Martin Maron of the Lahey Hospital and Medical Heart, Burlington, Massachusetts, US.

“HCM sufferers are sometimes on a number of drugs, which continuously present suboptimal profit, whereas aficamten was extremely efficient at offering medical enchancment as mixture remedy, but in addition as monotherapy.”

HCM happens in roughly one in 200 to 500 people, with 70% of sufferers having obstructive illness. The situation causes the partitions of the left ventricle to turn into thick and stiff, which might additionally end in obstruction to blood movement out of the center and elevated intracardiac pressures.

Aficamten is a cardiac myosin inhibitor that was beforehand proven to scale back LVOT gradients in a part 2 trial. The part 3 SEQUOIA-HCM trial evaluated the efficacy and security of aficamten versus placebo in adults with symptomatic obstructive HCM.

The first endpoint was the change in pVO2, assessed utilizing cardiopulmonary train testing, from baseline to week 24. Secondary endpoints at 24 weeks included the change in KCCQ rating; the proportion of sufferers with ≥1 class enchancment in New York Coronary heart Affiliation (NYHA); change in Valsalva LVOT gradient; the proportion of sufferers with Valsalva LVOT gradient <30 mmHg; and eligibility for invasive septal discount.

SEQUOIA-HCM included 282 sufferers from 101 websites in 14 nations in North America, Asia, and Europe, making it the largest-ever obstructive HCM trial. All contributors had lowered train capability resulting from obstructive HCM.

Sufferers have been randomized 1:1 to aficamten or placebo on prime of their background medical remedy. The beginning dose of aficamten was 5 mg as soon as every day with alternatives at weeks 2, 4, and 6 to extend the dose in 5 mg increments to a most dose of 20 mg. Dose changes have been made in keeping with left ventricular ejection fraction and LVOT gradients assessed utilizing echocardiography.

The imply enhance in pVO2 from baseline to 24 weeks was 1.8 ml/kg/min with aficamten in comparison with 0.0 ml/kg/min with placebo (least-squares imply distinction between teams, 1.7 ml/kg/min; 95% confidence interval [CI] 1.0, 2.4; p<0.001). Concerning secondary endpoints at 24 weeks, aficamten resulted in a least-squares imply distinction of seven factors in KCCQ rating relative to placebo (95% CI 5, 10; p<0.0001).

A ≥1 NYHA class enchancment was noticed in 58.5% of sufferers on aficamten and 24.3% of sufferers on placebo (p<0.0001). Aficamten led to a 50 mmHg better discount in Valsalva LVOT gradient versus placebo (95% CI -57, -44; p<0.0001). Some 49.3% of sufferers on aficamten achieved a Valsalva LVOT gradient <30 mmHg versus 3.6% of sufferers on placebo (p<0.0001). The aficamten group had 78 fewer days eligible for invasive septal discount in contrast with the placebo group (p<0.0001).

Professor Maron mentioned, “It was spectacular to see that the helpful results of aficamten occurred quickly and persistently over the therapy interval and that the doses may very well be adjusted successfully and safely utilizing solely website learn echocardiographic measures.

“It was additionally reassuring to see that within the very small variety of sufferers discovered to have an ejection fraction under 50% on aficamten, there was no related coronary heart failure or the necessity for dose interruption, and that the impact on ejection fraction was reversible with therapy discontinuation.”