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Randomized Controlled Trial
. 2025 May 13;151(19):1378-1390.
doi: 10.1161/CIRCULATIONAHA.124.072445. Epub 2024 Nov 18.

Mavacamten in Patients With Hypertrophic Cardiomyopathy Referred for Septal Reduction: Week 128 Results From VALOR-HCM

Milind Y Desai  1   2   3 , Kathy Wolski  2   3 , Anjali Owens  4 , Jeffrey B Geske  5 , Sara Saberi  6 , Andrew Wang  7 , Mark Sherrid  8 , Paul C Cremer  2   3 , Neal K Lakdawala  9 , Albree Tower-Rader  10 , David Fermin  11 , Srihari S Naidu  12 , Nicholas G Smedira  1   13 , Hartzell Schaff  14 , Zhiqun Gong  15 , Lana Mudarris  15 , Kathy Lampl  15 , Amy J Sehnert  12   15 , Steven E Nissen  2   3 ; VALOR-HCM Investigators
Affiliations
Randomized Controlled Trial

Mavacamten in Patients With Hypertrophic Cardiomyopathy Referred for Septal Reduction: Week 128 Results From VALOR-HCM

Milind Y Desai et al. Circulation. .

Erratum in

Abstract

Background: In severely symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM), VALOR-HCM trial (Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive HCM Who Are Eligible for Septal Reduction Therapy [URL: https://clinicaltrials.gov; Unique identifier: NCT04349072]) reported that mavacamten reduced the short-term need for septal reduction therapy (SRT). The current report examined the longer-term effect of mavacamten through end of treatment at week 128.

Methods: A double-blind randomized placebo-controlled multicenter trial at 19 sites in the United States included symptomatic obstructive HCM patients referred for SRT (enrollment July 2020 through October 2021). The group initially randomized to mavacamten continued the drug for 128 weeks and the placebo to mavacamten group from week 16 to 128 (112-week exposure). Dose titrations were performed using echocardiographic left ventricular outflow tract gradient and left ventricular ejection fraction measurements. The principal end point was proportion of patients proceeding with SRT or remaining guideline-eligible at week 128.

Results: At week 128, 17 of 108 (15.7%) patients in the total study sample met the composite end point (7 underwent SRT, 1 was SRT-eligible, and 9 SRT-status unevaluable). Additionally, 87 of 108 (80.5%) patients demonstrated ≥1 New York Heart Association class improvement by week 128, and 52 of 108 (48.1%) demonstrated ≥2, with a sustained reduction in resting and Valsalva left ventricular outflow tract gradients of 38.2 mm Hg and 59.4 mm Hg, respectively. Ninety-five of 108 (88%) patients transitioned to commercial mavacamten. Overall, 15 of 108 (13.8%) patients (5.41 per 100 patient-years) had an left ventricular ejection fraction <50% (2 with left ventricular ejection fraction ≤30%; 1 death). Of these, 12 of 15 (80%) continued treatment. New-onset atrial fibrillation occurred in 11 (10.2%) patients (4.55 per 100 patient-years).

Conclusions: In severely symptomatic obstructive HCM patients, sustained freedom from SRT was observed at 128 weeks, with nearly 90% patients remaining on long-term mavacamten.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04349072.

Keywords: cardiomyopathy, hypertrophic; mavacamten; septal reduction.

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Conflict of interest statement

M. Desai reports consulting for Bristol Myers Squibb, Cytokinetics, Tenaya, and Medtronic; and research support to Cleveland Clinic from Bristol Myers Squibb, Cytokinetics, and Tenaya. A. Owens reports consulting for Bristol Myers Squibb, Cytokinetics, Pfizer, Biomarin, Tenaya, Lexicon, Stealth, Edgewise, and Renovacor; and receives grant support for research from Bristol Myers Squibb. Dr Saberi reports consulting for Bristol Myers Squibb and Cytokinetics. Dr Lakdawala has received consulting incomes from Bristol Myers Squibb, Pfizer, Tenaya, Cytokinetics and Akros and research support from Bristol Myers Squibb and Pfizer. Drs Naidu, Wang, Sherrid, and Tower-Rader report consulting for Bristol Myers Squibb and Cytokinetics. Drs Smedira and Geske report consultation with Bristol Myers Squibb. Dr Fermin reports conflicts from Bristol Myers Squibb (consulting, speaking), Pfizer (consulting), BridgeBio (consulting, speaking). Drs Nissen and Wolski work for C5 Research and are employees of Cleveland Clinic, which received payments for the present research from Bristol Myers Squibb. Drs Gong, Mudarris, Sehnert, and Lampl are employees of Bristol Myers Squibb. Dr Cremer was employed during the conduct of the trial by Cleveland Clinic, which received payments for current research from Bristol Myers Squibb. The other authors report no conflicts.

Figures

Figure 1.
Figure 1.
Primary and key efficacy parameters from baseline to week 128 in VALOR-HCM trial. A, Primary composite end point from baseline to week 128. B, Improvement in New York Heart Association (NYHA) class from baseline to week 128. SRT indicates septal reduction therapy; and VALOR-HCM, Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive HCM Who Are Eligible for Septal Reduction Therapy.
Figure 2.
Figure 2.
Key echocardiographic efficacy and safety parameters from baseline to week 128 for the original mavacamten and the placebo to mavacamten groups. A, Change in left ventricular (LV) ejection fraction. B, Improvement in peak left ventricular outflow tract (LVOT) gradient at rest. C, Improvement in peak left ventricular outflow tract gradient after Valsalva maneuver. D, Improvement in peak left ventricular outflow tract gradient after stress echocardiography. Plotted values in B through D represent means and standard errors.
Figure 3.
Figure 3.
Additional echocardiographic parameters from baseline to week 128 demonstrating favorable cardiac remodeling for the original mavacamten and the placebo to mavacamten groups. A, Improvement interventricular wall thickness. B, Improvement in left ventricular mass index. C, Improvement in left atrial volume index. D, Improvement in E/e’. Plotted values in B through D represent means and standard errors.
Figure 4.
Figure 4.
Changes in biomarkers and health status from baseline to week 128 demonstrating favorable cardiac remodeling for the original mavacamten and the placebo to mavacamten. A, Improvement in Kansas City Cardiomyopathy Questionnaire 23-Item Clinical Summary Score (KCCQ-23 CSS). B, Improvement NT-pro-BNP (N-terminal pro brain natriuretic peptide). C, Improvement in cTn-I (troponin I).
See this image and copyright information in PMC

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