Aficamten Hits the Mark in Nonobstructive HCM: ACACIA-HCM

 Breaking HCM Phase 3 Trial

Clinical Trial Results

Topline results show significant gains in quality-of-life scores and peak oxygen consumption — a first for this harder-to-treat form of the disease.

Aficamten (Myqorzo; Cytokinetics), a selective cardiac myosin inhibitor, has become the first therapy to demonstrate meaningful benefit in nonobstructive hypertrophic cardiomyopathy (HCM) — a population that has long lacked effective pharmacological options.¹

Topline results from the pivotal ACACIA-HCM trial showed that after 36 weeks, patients randomized to aficamten achieved statistically significant improvements across both dual primary endpoints: patient-reported quality of life and objective exercise capacity.¹

Primary Endpoints at 36 Weeks — Least Squares Mean

KCCQ Clinical Summary Score

+11.4 vs +8.4

Aficamten vs Placebo P = 0.021

Peak O₂ Consumption (mL/kg/min)

+0.64 vs −0.03

Aficamten vs Placebo P = 0.003

KCCQ = Kansas City Cardiomyopathy Questionnaire. Secondary endpoints including NYHA functional class and NT-proBNP also improved significantly.

KCCQ improvements emerged around week 8 and were maintained through 72-week follow-up. Both aficamten and mavacamten (Camzyos; Bristol Myers Squibb) are currently approved for obstructive HCM; however, the ODYSSEY-HCM trial previously failed to show benefit with mavacamten in nonobstructive patients.² ACACIA-HCM — enrolling 516 patients — changes that picture.

Safety Profile

⚠ Safety NoteLVEF below 50% occurred in 10% of aficamten-treated patients vs 1% on placebo. Two patients had serious heart failure events associated with LVEF reduction; 3% discontinued due to LVEF below 40%. Both aficamten and mavacamten carry boxed warnings for systolic dysfunction, with echocardiographic monitoring required before and during treatment.

The higher rate of LVEF reduction reflects a key design difference: in nonobstructive HCM, the study escalated aficamten to a maximally tolerated dose (up to 20 mg), rather than the minimum effective dose strategy used in obstructive disease.¹ Comparable proportions in both arms completed planned dosing, and most participants transitioned to an open-label registry at study end.

What Comes Next

Full results will be presented at a major cardiology meeting. If approved, aficamten would become the first drug ever indicated for nonobstructive HCM — addressing a significant unmet need.

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References

1. Cytokinetics. Cytokinetics announces positive topline results from ACACIA-HCM, the pivotal phase 3 clinical trial of aficamten in patients with nonobstructive hypertrophic cardiomyopathy. Press release. May 5, 2026. Available at: ir.cytokinetics.com
2. TCTMD. Mavacamten strikes out in phase III trial for nonobstructive HCM (ODYSSEY-HCM). Available at: tctmd.com
3. ClinicalTrials.gov. ACACIA-HCM study (NCT06081894). Available at: clinicaltrials.gov/study/NCT06081894