What happened
Aficamten improves quality of life scores by 3 points and exercise capacity vs placebo at 36 weeks.
“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.”
Dr. Ahmad Masri
A long-awaited positive trial, but the effect is modest and LVEF monitoring matters.
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She questions whether a 3-point KCCQ gain is clinically relevant.
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He notes nonobstructive HCM has few disease-specific options and an earlier phase 3 trial of mavacamten in this group was neutral.
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She highlights a >10% improvement in septal e' in 1/4 of patients and echoes the discussant's question about which phenotypes benefit most.
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She calls aficamten the first drug to beat placebo in a phase 3 trial in nonobstructive HCM.
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Heart Failure · Brigham and Women's Hospital
We are grateful to the patient community and the clinical trial team who contributed to the successful completion of ACACIA-HCM, a fitting tribute to the patients and families who have struggled with this disease for many years and across generations. We are also pleased that most of the eligible patients from ACACIA-HCM are continuing treatment with aficamten in FOREST-HCM. We look forward to applying this study's groundbreaking scientific knowledge into clinical practice upon potential approval, addressing this area of HCM where patients do not have adequate treatment options.
ACACIA-HCM co-authorHeart Failure · Brigham and Women's Hospital
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.
ACACIA-HCM co-author$CYTK ACACIA-HCM is the First Phase 3 Clinical Trial to Successfully Demonstrate Statistically Significant Improvements Across Both Patient-Reported and Physician-Assessed Endpoints in Non-Obstructive HCM Supplemental New Drug Application to be Submitted to FDA in Fourth Quarter
t.coACACIA-HCMHeart Failure · Brigham and Women's Hospital
Today was a special day. We reported the results of 2 pivotal trials in HCM and in transthyrtin amyloidosis. My passion for both —and for the patients affected by these diseases—came full circle. More trials on Sunday - stay tuned ACACIA-HCM
t.cot.coACACIA-HCM co-authorHeart Failure · Brigham and Women's Hospital
We presented the ACACIA-HCM trial. A milestone for us and our patients, having a therapy that influences many important clinical domains that are relevant to patients and physicians alike. This is the start in nHCM. An impactful one. Paper simultaneously published in @NEJM
t.coACACIA-HCM co-authorRemarkable results from ACACIA HCM. Incredible news for our patients with non-obstructive Hypertrophic Cardiomyopathy. #PrecisionCVM
t.coACACIA-HCMMore than half of aficamten-treated patients achieved improvement across three or more of the five clinical, functional and biological measures evaluated, compared with 13% of placebo-treated patients.
ACACIA-HCM
Heart Failure · Brigham and Women's Hospital
The additional results from ACACIA-HCM suggest that the benefits of aficamten in non-obstructive HCM extend beyond exercise capacity and symptom burden to also include improvements in wall thickness and diastolic function, pointing to the potential mechanisms by which aficamten is effective in these patients. Given the lack of approved therapies for non-obstructive HCM, these findings highlight the potential impact aficamten could have on this population independent from relief of left ventricular outflow tract obstruction.
ACACIA-HCM
Heart Failure · Brigham and Women's Hospital
The frequency of these findings is not surprising relative to those with aficamten in [obstructive] HCM given the strategy in nonobstructive HCM to dose to a maximally tolerated dose as opposed to a minimum effective dose.
ACACIA-HCMHeart Failure · Brigham and Women's Hospital
ACACIA-HCM is the first-ever positive clinical trial in non-obstructive HCM. As shown in presentation and publication, the results from ACACIA-HCM are both statistically robust, consistent across prespecified subgroups and other secondary endpoints, and clinically impactful for these patients with non-obstructive HCM. As such, these data may potentially translate into a new treatment option for patients with HCM with no available medical treatments that directly address their underlying disease. If approved, we look forward to seeing aficamten become the first cardiac myosin inhibitor to treat the full spectrum of symptomatic HCM.
ACACIA-HCMHeart Failure · Brigham and Women's Hospital
Patients with non-obstructive 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. We believe that the totality and consistency of evidence favoring aficamten across multiple patient-reported and physician-assessed endpoints of symptom improvement and physical function are clinically meaningful for patients with non-obstructive HCM.
ACACIA-HCM
Heart Failure · Universität Hamburg
nHCM patients remain symptomatic despite current heart-failure-guideline-based care and have lacked a targeted therapy.
ACACIA-HCM$CYTK "Among patients with symptomatic nonobstructive HCM, treatment with aficamten resulted in a significantly greater change in exercise capacity and patient-reported health status than placebo at 36 weeks." Primary endpoints below. $BMY $MYOK
t.cot.cot.coACACIA-HCM$CYTK A few of our thoughts on ACACIA-HCM data this morning after some time to digest (pending additional physician feedback): ➡️KCCQ data positive & stat sig as previously disclosed, with the delta diverging from +3.1 vs. placebo at wk36 (p=0.021) to +7.0 by wk72 (p<0.005) -
t.coACACIA-HCMCytokinetics, $CYTK: Comments on today's data: ACACIA-HCM is a real but modest win: dual primaries hit (KCCQ +3.0, pVO2 +0.67), first positive nHCM Phase 3, sNDA in Q4, but the KCCQ delta is below the usual 5-point MCID, hard events and remodeling missed, and serious HF was 4.3%
ACACIA-HCM
Interventional Cardiology
Aficamten for Symptomatic Nonobstructive Hypertrophic Cardiomyopathy: @NEJM @escardio 🥸 Congratulations to @MasriAhmadMD and team. 😱 Summary #ESCCongress2026 👇👇👇
t.coACACIA-HCM@ESC_Journals Aficamten first drug for non-obstructive HCM to change outcomes ACACIA-HCM - KCCQ-CSS LSM difference +3.0 (0.5–5.5), p=0.021 - pVO2 +0.67 mL/kg/min (0.22–1.1), p=0.003. - LVEF <50% in 10% vs 1%; two HF SAEs with LVEF <50% on drug; dose interruptions for LVEF
ACACIA-HCM
General · Cedars-Sinai Medical Center
🫀 #ACACIAHCM at #ESCCongress Can we finally improve symptoms AND exercise capacity in symptomatic non-obstructive #HCM? 516 patients Aficamten 🆚 placebo ⏱️ 36 weeks 🌟both primary endpoints were positive: ➡️ KCCQ-CSS: +3.0 vs placebo (P=.021) ➡️ Peak VO₂: +0.67 mL/kg/min
t.coACACIA-HCMOpen questions from this trial that would benefit from expert input.
Answers are grounded in this paper and cite their sources.
Why the trial, tables, limitations, PICO, abstract, media & sources
Symptomatic nonobstructive hypertrophic cardiomyopathy has no approved disease-specific therapy, and cardiac myosin inhibition had only been proven in obstructive disease. ACACIA-HCM asked whether aficamten improves symptoms and exercise capacity when there is no outflow gradient to relieve.
Does aficamten improve exercise capacity and patient-reported health status in adults with symptomatic nonobstructive hypertrophic cardiomyopathy?
| Outcome | Aficamten | Placebo |
|---|---|---|
| KCCQ-CSS change at week 36 Dual primary - LS mean difference 3.0 points (95% CI 0.5-5.5); P=0.02 | Aficamten +11.4 | Placebo +8.4 |
| Peak VO2 change at week 36 (ml/kg/min) Dual primary - LS mean difference 0.67 (95% CI 0.22-1.11); P=0.003 | Aficamten +0.64 | Placebo -0.03 |
Does aficamten improve exercise capacity and patient-reported health status in adults with symptomatic nonobstructive hypertrophic cardiomyopathy?
In patients with symptomatic nonobstructive hypertrophic cardiomyopathy, aficamten significantly improved exercise capacity and patient-reported health status at 36 weeks compared to placebo.
Experts agree aficamten delivered the first positive trial in symptomatic nonobstructive HCM, but several call the benefit modest and want long-term safety and outcome data before calling it practice-changing.
Clinicians welcome a long-awaited win in a patient group that has had no targeted therapy and a history of neutral trials. The split is over size: the trial's leaders call the gains clinically meaningful, while independent readers say the symptom improvement is small and flag heart function drops and early heart failure events on the drug. The live question is which patients benefit most and whether the effect holds up over the long term.
Clinicians across the reaction describe ACACIA-HCM as the first positive trial of a drug in nonobstructive HCM, coming after earlier neutral efforts.
Clinically meaningful gain or a real but modest win?
What they’re arguing about
supportiveneutralcautiouscritical
Counts are expert takes we classified by axis. Tap a row to see the takes behind its count.
Experts ask which phenotypes are most likely to benefit and whether long-term safety and clinical outcomes will hold up, with cardiovascular events not reduced in this trial. Some point to FOREST-HCM for longer-term data.
Provides first targeted option for symptomatic nonobstructive HCM; extends myosin inhibition beyond obstructive disease.
BACKGROUND: Nonobstructive hypertrophic cardiomyopathy (HCM) is a common condition that is associated with substantial morbidity and no proven medical therapy. Whether treatment with aficamten, a cardiac myosin inhibitor, can benefit patients with this condition is unknown. METHODS: In this phase 3, multinational, double-blind trial, we randomly assigned adults with symptomatic nonobstructive HCM in a 1:1 ratio to receive aficamten (starting dose, 5 mg; maximum dose, 20 mg) or placebo for up to 72 weeks. The dual primary end points were the change from baseline to week 36 in peak oxygen uptake and in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS; range, 0 to 100, with higher scores indicating better health status). RESULTS: A total of 258 patients were assigned to receive aficamten and 259 to receive placebo. The mean age of the patients was 55.1 years, and 53.6% were women. At 36 weeks, the change in the KCCQ-CSS was 11.4 points (95% confidence interval [CI], 9.6 to 13.2) in the aficamten group and 8.4 points (95% CI, 6.6 to 10.2) in the placebo group (least-squares mean difference, 3.0 points; 95% CI, 0.5 to 5.5; P = 0.02). The mean change in the peak oxygen uptake at week 36 was 0.64 ml per kilogram of body weight per minute (95% CI, 0.32 to 0.95) in the aficamten group and -0.03 ml per kilogram per minute (95% CI, -0.35 to 0.28) in the placebo group (least-squares mean difference, 0.67 ml per kilogram per minute; 95% CI, 0.22 to 1.11; P = 0.003). Reversible reductions in left ventricular ejection fraction to less than 50% occurred in 27 patients (10.5%) receiving aficamten and in 2 patients (0.8%) receiving placebo. Serious adverse events occurred in 52 patients (20.2%) and 38 patients (14.7%), respectively. CONCLUSIONS: Among patients with symptomatic nonobstructive HCM, treatment with aficamten resulted in a significantly greater change in exercise capacity and patient-reported health status than placebo at 36 weeks. (Funded by Cytokinetics; ACACIA-HCM ClinicalTrials.gov number, NCT06081894.).
Journal, society, and media accounts. Useful signal, not independent expert judgment.
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 improved quality of life and exercise capacity compared to placebo at 36 weeks in nonobstructive HCM.
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