August 27, 2025Journal of the American College of Cardiology
Effects of Mavacamten on Cardiac Biomarkers in Nonobstructive Hypertrophic Cardiomyopathy
Milind Y. DesaiIacopo OlivottoTheodore P. AbrahamSteven E. NissenPablo García‐PavíaRenato D. LópesPerry ElliottFábio FernandesEdileide de Barros CorreiaRoberto Barriales‐VillaEsther ZorioMichael AradSung‐Hee ShinNicolas VerheyenBenjamin MederOlga AzevedoHiroaki KitaokaKathy WolskiQiuqing WangBharat SuryawanshiZhaoqing WangVictoria FloreaRon AronsonAnjali Owens
Key result
Mavacamten cuts NT-proBNP by ~58% vs placebo in symptomatic nonobstructive HCM.
- Geometric mean ratio 0.42
- 95% CI 0.37-0.47
- P<0.001
- n=580
Why the study?
No therapy is approved for symptomatic nonobstructive hypertrophic cardiomyopathy, and the role and response of cardiac biomarkers with mavacamten needed evaluation.
Does mavacamten reduce cardiac biomarkers in symptomatic adults with nonobstructive hypertrophic cardiomyopathy?
Study Design
Type
RCT (n=580)
Randomization
randomized
Structured PICO
Does mavacamten reduce cardiac biomarkers in symptomatic adults with nonobstructive hypertrophic cardiomyopathy?
P
Population
580 symptomatic adults with nonobstructive hypertrophic cardiomyopathy, mean age 56 years, followed for 48 weeks.
I
Intervention
Mavacamten (starting at 5 mg/d, with titration ranging from 1 to 15 mg, based on left ventricular ejection fraction) for 48 weeks
C
Comparator
Placebo
O
Outcome
Changes in NT-proBNP and hs-cTnI from baseline to week 48surrogate
Main Result
Effect estimate: Geometric mean ratio 0.42 (95% CI 0.37-0.47)
p-value: p=<0.001
Limitations
- Whether these changes translate into longer-term adaptive remodeling and improvements in patient-reported health status, exercise capacity, and outcomes remain to be ascertained.
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“whether these changes translate into longer-term adaptive remodeling and improvements in patient-reported health status, exercise capacity, and outcomes”
Implication
In symptomatic nonobstructive hypertrophic cardiomyopathy, mavacamten significantly reduced NT-proBNP and hs-cTnI over 48 weeks compared to placebo, despite the main trial not meeting its primary clinical endpoints.
Abstract
BACKGROUND No therapy is approved for patients with symptomatic nonobstructive hypertrophic cardiomyopathy (nHCM). The ODYSSEY-HCM (A Study of Mavacamten in Non-Obstructive Hypertrophic Cardiomyopathy [ODYSSEY-HCM]; NCT05582395) trial, the largest to date in patients with hypertrophic cardiomyopathy (HCM), evaluating the efficacy of mavacamten in symptomatic adults with nHCM, did not demonstrate improvements in its primary endpoints (functional capacity and patient-reported health status). OBJECTIVES The current exploratory analysis from the ODYSSEY-HCM trial reports the associations between: 1) baseline biomarkers (N-terminal pro-B-type natriuretic peptide [NT-proBNP] and high-sensitivity cardiac troponin I [cTnI]) with clinical, exercise, and echocardiographic characteristics; and 2) comparing changes in these biomarkers from baseline to week 48 between mavacamten and placebo groups. METHODS Symptomatic nHCM patients were randomized to placebo or mavacamten (starting at 5 mg/d, with titration ranging from 1 to 15 mg, based on left ventricular [LV] ejection fraction). Along with clinical and echocardiographic parameters, NT-proBNP and hs-cTnI were measured for changes from baseline to week 48. RESULTS Among 580 randomized patients (mean age 56 ± 15 years, 266 [45.9%] women), baseline biomarkers were elevated with median NT-proBNP 917.5 ng/L (IQR: 463-1,725 ng/L) and hs-cTnI of 29.1 ng/L (IQR: 14.4-91.7 ng/L). On multivariable analysis, female sex, body mass index, NYHA functional class, maximal LV wall thickness, left atrial volume index, and E/e' were associated with higher baseline NT-proBNP. Only younger age and LV mass index were associated with higher baseline hs-cTnI level. At week 48, the mavacamten group had a 58% reduction in NT-proBNP (geometric mean ratio: 0.42; 95% CI: 0.37-0.47; P < 0.001) and a 51% reduction in hs-cTnI (geometric mean ratio: 0.49; 95% CI: 0.45-0.53; P < 0.001). No significant change in either biomarker was seen in the placebo group. These reductions occurred early and were maintained through week 48. CONCLUSIONS Treatment with mavacamten for 48 weeks in nHCM patients was associated with marked biomarker improvements compared with placebo. Whether these changes translate into longer-term adaptive remodeling and improvements in patient-reported health status, exercise capacity, and outcomes remain to be ascertained. (A Study of Mavacamten in Non-Obstructive Hypertrophic Cardiomyopathy [ODYSSEY-HCM]; NCT05582395).
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Cite This Study
Desai et al. (2025) conducted an RCT in symptomatic nonobstructive hypertrophic cardiomyopathy (nHCM) (n=580). Mavacamten vs. placebo was evaluated on Change in NT-proBNP from baseline to week 48 (Geometric mean ratio 0.42, 95% CI 0.37-0.47, p=<0.001). Mavacamten treatment for 48 weeks in symptomatic nonobstructive hypertrophic cardiomyopathy significantly reduced NT-proBNP by 58% (geometric mean ratio 0.42; 95% CI 0.37-0.47; P<0.001) versus placebo.