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Real-world long-term effectiveness of mavacamten in patients with symptomatic obstructive hypertrophic cardiomyopathy: a multicenter observational study (MARVEL-HCM)

Theodore Abraham,1 Said Alsidawi,2 Matthew W Martinez,3 Matthew T Wheeler,4 Kaitlin Roehl,2 Ruchi Patel,4 Marybeth Soutar,3 Morgane Herry,1 Manchen Wang,1 Mi-Ok Kim,1 Patricia Schuler,5 Anandkumar Dubey5

1University of California San Francisco, San Francisco, CA, US; 2Mayo Clinic Arizona, Phoenix, AZ, US; 3Atlantic Health System/Morristown Medical Center, Morristown, NJ, US; 4Stanford University School of Medicine, Stanford, CA, US; 5Bristol Myers Squibb, Princeton, NJ, US

Presented at the American Heart Association Scientific Sessions 2024; November 16–18, 2024, Chicago, IL, US

Contact: www.globalbmsmedinfo.com

Background

  • Mavacamten, a first-in-class cardiac myosin inhibitor, was approved by the US Food and Drug Administration in April 2022 for the treatment of adults with symptomatic New York Heart Association (NYHA) class II–III obstructive hypertrophic cardiomyopathy (HCM) to improve functional capacity and symptoms1
  • Studies reporting the long-term, real-world effectiveness and safety profile of mavacamten are limited
  • The MavAcamten Real world eVidEnce coLlaboration in HCM (MARVEL-HCM) is a multicenter observational study in the US that aims to describe the real-world effectiveness and safety profile of mavacamten in patients with symptomatic obstructive HCM

Methods

  • Patient-level electronic medical records (EMRs) from April 2022 to January 2024 were analyzed retrospectively from 4 sites in the US: the University of California San Francisco; Stanford Health Care; Atlantic Health System/Morristown Medical Center; and Mayo Clinic Arizona
  • Adult patients were eligible for inclusion if they had NYHA class II–III symptoms, were prescribed mavacamten for the treatment of symptomatic obstructive HCM during the identification period, and had been receiving treatment for at least 12 weeks
  • The index date was the first date of mavacamten prescription recorded in the EMR during the identification period
  • Patients were assessed at baseline (defined as the last visit before mavacamten initiation) and for up to 72 weeks of mavacamten treatment to evaluate the effect of mavacamten on resting and Valsalva left ventricular outflow tract (LVOT) gradients, NYHA functional class, and left ventricular ejection fraction (LVEF)

Results (1/4)

  • In total, 172 patients were treated with mavacamten during the study period
  • Baseline clinical and demographic characteristics are presented in Table 1
    • The mean age was 63.9 years, 56.4% were female, and 77.3% were White
    • Common comorbidities included hypertension (57.0%) and atrial fibrillation (26.2%)
    • Patients with evaluable data had either NYHA class II (53.5%) or class III (46.5%) symptoms, and had severe obstruction (mean [SD] Valsalva LVOT gradient: 85.8 [40.0] mm Hg; n = 168)

Table 1. Baseline clinical and demographic characteristics

Characteristic Patient population (N = 172)
Age, years

Mean (SD)
Median (minimum, maximum)
63.9 (13.3)
67.0 (21.0, 87.0)
Sex, female, n (%) 97 (56.4)
Race, n (%)

White
Asian
Black
Other/unknown
133 (77.3)
17 (9.9)
8 (4.7)
14 (8.1)
HCM background therapy, n (%)

Beta-blocker monotherapy
Calcium channel blocker monotherapy
Disopyramide monotherapy
Combination therapy
None
106 (61.6)
17 (9.9)
0
31 (18.0)
18 (10.5)
Starting dose of mavacamten, n (%)

5 mg
172 (100)
BMI, kg/m2, mean (SD) 29.6 (6.3)
Family history of HCM, n (%) 23 (13.4)
Duration of HCM, years, mean (SD) [n = 119] 6.8 (5.4)
Medical history, n (%)

Hypertension
Atrial fibrillation
Coronary artery disease
Diabetes
98 (57.0)
45 (26.2)
24 (14.0)
23 (13.4)
LVOT gradient, mm Hg, mean (SD)

Resting [n = 167]
Valsalva [n = 168]
48.2 (35.2)
85.8 (40.0)
LVEF, %, mean (SD) 68.5 (5.3)
NYHA functional class, n (%)

NYHA class II
NYHA class III
92 (53.5)
80 (46.5)

BMI, body mass index; SD, standard deviation.

Results (2/4)

  • Mavacamten was associated with a rapid reduction in resting and Valsalva LVOT gradients by week 4, which were sustained through to week 72 (Figure 1)

Long-term mavacamten treatment in patients with obstructive HCM resulted in early and sustained improvements in resting and Valsalva LVOT gradients

Figure 1. Mean resting and Valsalva LVOT gradients over 72 weeks of mavacamten treatment

Error bars show SDs.
The dotted line represents the threshold for nonobstruction.

Results (3/4)

  • The proportion of patients with NYHA class III symptoms decreased from 46.5% at baseline (80/172 patients) to 7.0% at week 24 (9/129 patients), 9.3% at week 36 (9/97 patients), and 0% at week 72 (Figure 2)
    • Conversely, the proportion of patients in NYHA class I increased from 0% at baseline to 48.8% at week 24 (63/129 patients), 51.5% at week 36 (50/97 patients), and 63.2% at week 72 (24/38 patients)
  • One patient (0.8%) had NYHA class IV symptoms at week 24; this patient transitioned to comfort care measures, owing to comorbidities

Figure 2. NYHA functional class distribution over 72 weeks of mavacamten treatment

Results (4/4)

  • There were no substantial changes in mean LVEF from baseline to week 72 (Figure 3)
    • Overall, 6 of 172 patients (3.5%) experienced a reduction in LVEF to < 50%, and no patient experienced a reduction in LVEF to < 30%

Figure 3. Mean LVEF over 72 weeks of mavacamten treatment

Error bars show SDs.
The dotted line represents the threshold for normal ejection fraction.

Limitations

  • This is an analysis from 4 centers (specialized in cardiovascular treatment and/or academic) across the US; consequently, the findings may not be generalizable to overall populations of patients with HCM in other types of centers or geographical areas
  • Data were observational; no particular considerations were taken for varying lengths of treatment/follow-up period

Conclusions

  • In this real-world multicenter observational study of mavacamten, early and sustained improvements in resting and Valsalva LVOT gradients and NYHA class were observed with mavacamten over 72 weeks of treatment
  • No considerable reductions in mean LVEF were observed, and 3.5% of patients experienced an LVEF of < 50%

Reference

  1. Bristol Myers Squibb. CAMZYOS (mavacamten) US prescribing information. 2024. Available from: https://packageinserts.bms.com/pi/pi_camzyos.pdf (Accessed September 29, 2024).

Acknowledgments

  • The authors would like to thank the patients and families who made this study possible and the study teams who participated
  • This study was supported by Bristol Myers Squibb
  • All authors contributed to and approved the poster; writing and editorial assistance was provided by Thomas Crighton PhD of Oxford PharmaGenesis, Oxford, UK, funded by Bristol Myers Squibb

Declaration of Interests

Theodore Abraham has received research grants to institution from Bristol Myers Squibb, Cytokinetics, Edgewise, Imbria, and Tenaya, and has served as a consultant for Edgewise. Said Alsidawi has received research grants from Bristol Myers Squibb and Cytokinetics, and has served as an advisory board member for BioMarin Pharmaceuticals. Matthew W Martinez has received consulting fees from Bristol Myers Squibb, Cytokinetics, and VIZ.ai. Matthew T Wheeler has received research support and in-kind medical writing support from Bristol Myers Squibb. Patricia Schuler and Anandkumar Dubey are employees of Bristol Myers Squibb and may own stock in Bristol Myers Squibb. Kaitlin Roehl, Ruchi Patel, Marybeth Soutar, Morgane Herry, Manchen Wang, and Mi-Ok Kim have no relevant competing interests to disclose