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August 29, 2026New England Journal of Medicine
Aficamten for Symptomatic Nonobstructive Hypertrophic Cardiomyopathy
Key result
Aficamten improves KCCQ scores by 3 points and peak VO2 vs placebo at 36 weeks.
- MD 3.0
- 95% CI 0.5 to 5.5
- P=0.02
- n=517
Why the study?
Does aficamten improve exercise capacity and patient-reported health status in adults with symptomatic nonobstructive hypertrophic cardiomyopathy?
Population
517 adults with symptomatic nonobstructive hypertrophic cardiomyopathy, mean age 55.1 years, 53.6% women…
Comparison
Aficamten for up to 72 weeks. vs Placebo for up to 72 weeks.
Design
RCT, 1:1 ratio, double-blind
Follow-up
36 weeks
Authors
Discussion
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Member takes
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
What they’re arguing about
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“Based on this trial, this is the first-ever successful therapy for nonobstructive hypertrophic cardiomyopathy. These results are highly encouraging for patients with this condition and for cardiologists who struggle to help them.”
“Results from the ACACIA-HCM trial provide really positive news for patients with symptomatic non-obstructive HCM. For the first time, we have shown clinically meaningful improvements in symptoms and exercise capacity with a treatment that targets the cause of the disease.”
“What I can say is that this is a positive clinical trial, and you have multiple domains of benefit. Every way, shape, or form you look at this, there was benefit that was derived from aficamten in a disease that has no treatments available right now.”
Implication
Provides first targeted option for symptomatic nonobstructive HCM; extends myosin inhibition beyond obstructive disease.
Key Points
- To evaluate the efficacy and safety of the cardiac myosin inhibitor aficamten in adults with symptomatic nonobstructive hypertrophic cardiomyopathy.
- Phase 3, multinational, double-blind randomized trial (ACACIA-HCM; NCT06081894) assigning 517 adults (258 aficamten, 259 placebo; mean age 55.1 years; 53.6% women) 1:1 to aficamten (5–20 mg) or placebo for up to 72 weeks.
- Assessed dual primary end points at week 36: change from baseline in peak oxygen uptake and in Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS).
- At 36 weeks, KCCQ-CSS increased by 11.4 points (95% CI, 9.6 to 13.2) with aficamten versus 8.4 points (95% CI, 6.6 to 10.2) with placebo (least-squares mean difference, 3.0 points; 95% CI, 0.5 to 5.5; P = 0.02).
- Peak oxygen uptake improved with aficamten compared to placebo at week 36 (mean change: 0.64 ml/kg/min [95% CI, 0.32 to 0.95] vs -0.03 ml/kg/min [95% CI, -0.35 to 0.28]; least-squares mean difference, 0.67 ml/kg/min; 95% CI, 0.22 to 1.11; P = 0.003).
- Reversible reductions in left ventricular ejection fraction below 50% occurred in 10.5% (27/258) of aficamten recipients versus 0.8% (2/259) in the placebo group, with serious adverse events reported in 20.2% versus 14.7% of patients, respectively.
Study Design
Type
RCT (n=517)
Blinding
Double-blind
Randomization
1:1
Multicenter
Yes
Structured PICO
Does aficamten improve exercise capacity and patient-reported health status in adults with symptomatic nonobstructive hypertrophic cardiomyopathy?
P
Population
517 adults with symptomatic nonobstructive hypertrophic cardiomyopathy, followed for up to 72 weeks.
I
Intervention
Aficamten (starting dose, 5 mg; maximum dose, 20 mg) for up to 72 weeks.
C
Comparator
Placebo for up to 72 weeks.
O
Outcome
Dual primary end points: change from baseline to week 36 in peak oxygen uptake and in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS).
Main Result
Mean Difference: 3 (95% CI 0.5–5.5)
Absolute Event Rate: 11.4% vs 8.4%
p-value: p=0.02
In patients with symptomatic nonobstructive hypertrophic cardiomyopathy, aficamten significantly improved exercise capacity and patient-reported health status at 36 weeks compared to placebo.
Coverage & sources
Journal, society, and media accounts. Useful signal, not independent expert judgment.
Cite This Study
Masri et al. (2026) conducted an RCT in Symptomatic nonobstructive hypertrophic cardiomyopathy (n=517). Aficamten vs. Placebo was evaluated on Change from baseline to week 36 in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) (MD 3.0, 95% CI 0.5 to 5.5, p=0.02). Aficamten significantly improved KCCQ-CSS (MD 3.0; 95% CI 0.5-5.5; P=0.02) and peak oxygen uptake (MD 0.67 ml/kg/min; P=0.003) compared to placebo at 36 weeks in nonobstructive HCM.