A Phase 3, Multi-Center, Randomized, Double-Blind Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy

doi:10.1056/nejmoa2603021

ACACIA-HCM

Paziente / Popolazione Intervento / Esposizione Confronto Esito

In 517 patients with symptomatic non-obstructive hypertrophic cardiomyopathy, aficamten improved KCCQ clinical summary score and peak oxygen uptake at 36 weeks compared with placebo.

N

517pazienti

Disegno

Phase 3 double-blind, placebo-controlled RCT, 1:1, echocardiography-guided dose titration at weeks 2, 4 and 6 (escalation only if LVEF ≥60%), primary analysis at week 36, treatment continued to 72 weeks

Esito

Dual primary — change from baseline to week 36 in KCCQ Clinical Summary Score and in peak oxygen uptake (pVO2)

Rilevanza

2Importante — uno dei diversi pilastri.

RisultatoKCCQ clinical summary score +11.4 vs +8.4 (P = 0.02) and peak oxygen uptake +0.64 vs −0.03 mL/kg/min (P = 0.003) at week 36. NYHA class, submaximal exercise and NT-proBNP also improved. LVEF fell below 50% in 10% vs 1%, managed by dose reduction.

Masri A, Maron MS, et al. N Engl J Med. 2026; published online 28 August. 10.1056/nejmoa2603021

Discussione e critica

The first positive randomised trial in non-obstructive hypertrophic cardiomyopathy, a population that has had no disease-modifying option. Both primary endpoints are met, but the between-group differences are small — 3.0 points on the KCCQ and 0.67 mL/kg/min of peak VO2 — around the edge of what a patient notices. Ten percent dropped below an ejection fraction of 50%, so the drug carries an echo surveillance programme with it, and 36 weeks is a short look at a lifelong disease.