Aficamten Demonstrates Efficacy in Nonobstructive HCM, Meeting Both Primary End Points in Phase 3 Trial

Cytokinetics announced positive topline results from ACACIA-HCM (NCT06081894), a pivotal phase 3 clinical trial evaluating aficamten (Myqorzo; Cytokinetics) in patients with symptomatic nonobstructive hypertrophic cardiomyopathy (nHCM). The data represent a significant milestone for a patient population that, until now, has had no approved pharmacologic therapies targeting the underlying disease mechanism.^1,2

Hypertrophic cardiomyopathy (HCM) is the most common monogenic inherited cardiovascular disorder, with more than 300,000 patients diagnosed in the United States and an estimated 400,000 to 800,000 additional patients who remain undiagnosed. Approximately half of all patients with HCM have the nonobstructive form of the disease, in which blood flow is not mechanically blocked but cardiac function remains significantly impaired. Despite carrying a substantial symptom burden, including exercise intolerance, dyspnea, and fatigue, patients with nHCM have historically had limited therapeutic recourse beyond symptomatic management with beta-blockers and calcium channel blockers.^1,3

Trial Design and Primary Endpoints

ACACIA-HCM was a multi-center, randomized, double-blind, placebo-controlled trial that enrolled 516 participants on a 1:1 basis with aficamten or placebo. The trial's dual primary end points were the change from baseline to week 36 in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) and maximal exercise performance as measured by peak oxygen uptake (pVO₂). Both end points were met with statistically significant improvements in favor of aficamten compared with placebo.¹

The KCCQ improvement was described as robust and consistent throughout the treatment period. Following a washout period, KCCQ scores in the aficamten group declined to match those of the placebo group, an effect that underscores the drug's reversibility, a pharmacologic property central to its design. At Week 36, pVO₂ increased among participants receiving aficamten while remaining unchanged in the placebo group.¹

Secondary End Points and Key Findings

Key secondary end points also demonstrated statistically significant improvement (P < .001), including the proportion of participants achieving at least a 1-class improvement in New York Heart Association (NYHA) Functional Class, a composite z-score of ventilatory efficiency and pVO₂, and NT-proBNP levels.¹

"Patients with nonobstructive HCM have no therapies approved to treat the underlying hypercontractility associated with the disease. We hope that will change with ACACIA-HCM, which is the first clinical trial to demonstrate statistically significant improvements in exercise capacity and symptom burden in patients with non-obstructive HCM," Fady I. Malik, MD, PhD, Cytokinetics' executive vice president of Research & Development, said in the news release.¹

Safety Profile

From a safety standpoint, no new signals were identified. Completion of planned dosing was similar across both arms (88.4% vs 90.3%). Left ventricular ejection fraction (LVEF) below 50% occurred in 10% of participants taking aficamten versus 1% on placebo, with 2 participants on aficamten experiencing a serious adverse event of heart failure associated with low LVEF. Treatment interruptions due to LVEF below 40% occurred in 3% of the aficamten arm.¹

Building on a Growing Evidence Base

Aficamten is already FDA-approved for symptomatic obstructive HCM (oHCM), a regulatory decision supported by data from the SEQUOIA-HCM (NCT05186818) and MAPLE-HCM trials (NCT05767346)—the latter of which was the first head-to-head comparison of a cardiac myosin inhibitor with a standard-of-care beta-blocker, demonstrating aficamten's superiority over metoprolol across all clinically relevant efficacy endpoints. The ACACIA-HCM results now position aficamten as a potential first approved therapy for nHCM, pending regulatory review. Cytokinetics stated it will present full results at an upcoming medical meeting and discuss findings with the FDA and international regulatory agencies.^1,4-7

Considerations for Pharmacists

Pharmacists dispensing aficamten should be aware that it is available only through the Myqorzo REMS Program due to the risk of heart failure from systolic dysfunction. The drug is metabolized primarily by CYP2C9, with clinically meaningful interactions possible with strong CYP2C9 inhibitors, multi-pathway inhibitors such as fluconazole or voriconazole, and CYP3A inducers, including the contraindicated rifampin.¹

REFERENCES

1. Cytokinetics announces positive topline results from ACACIA-HCM, the pivotal Phase 3 clinical trial of aficamten in patients with non-obstructive hypertrophic cardiomyopathy. News Release. Cytokinetics. Published May 5, 2026. Accessed May 5, 2026. https://ir.cytokinetics.com/press-releases/press-release-details/2026/Cytokinetics-Announces-Positive-Topline-Results-from-ACACIA-HCM-the-Pivotal-Phase-3-Clinical-Trial-of-Aficamten-in-Patients-with-Non-Obstructive-Hypertrophic-Cardiomyopathy/default.aspx

2. Phase 3 trial to evaluate the efficacy and safety of aficamten compared to placebo in adults with symptomatic nHCM (ACACIA-HCM). ClincialTrials.gov Identifier: NCT06081894. Last Updated February 2, 2026. Accessed May 5, 2026. http://clinicaltrials.gov/study/NCT06081894

3. Halpern L. Aficamten receives FDA approval for obstructive hypertrophic cardiomyopathy. Pharmacy Times. Published December 22, 2025. Accessed May 5, 2026. https://www.pharmacytimes.com/view/aficamten-receives-fda-approval-for-obstructive-hypertrophic-cardiomyopathy

4. Gerlach A. FDA approved NDA for aficamten to treat patients with obstructive hypertrophic cardiomyopathy. Pharmacy Times. Published May 16, 2025. Accessed May 5, 2026. https://www.pharmacytimes.com/view/fda-approved-nda-for-aficamten-to-treat-patients-with-obstructive-hypertrophic-cardiomyopathy

5. Fifer M, Valletti D. Aficamten emerges as a potential first-line therapy in hypertrophic cardiomyopathy. Pharmacy Times. Published September 10, 2025. Accessed May 5, 2026. https://www.pharmacytimes.com/view/aficamten-emerges-as-a-potential-first-line-therapy-in-hypertrophic-cardiomyopathy

6. Aficamten vs placebo in adults with symptomatic obstructive hypertrophic cardiomyopathy (SEQUOIA-HCM). ClinicalTrials.gov. Updated February 27, 2025. Accessed May 5, 2026. https://clinicaltrials.gov/study/NCT05186818

7. Phase 3 trial to evaluate the efficacy and safety of aficamten compared to metoprolol succinate in adults with symptomatic oHCM (MAPLE-HCM). ClinicalTrials.gov. Updated May 2, 2025. Accessed May 5, 2026. https://clinicaltrials.gov/study/NCT05767346