New Evidence, Guidelines Support Mavacamten Use in Hypertrophic Cardiomyopathy

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A trio of studies and new guidelines presented at the ESC Congress 2023 highlight advancement in the management of hypertrophic cardiomyopathy, particularly with use of mavacamten.

At the European Society of Cardiology (ESC) Congress 2023, the spotlight was on mavacamten and its role in obstructive hypertrophic cardiomyopathy (HCM).

Pushing it onto centerstage was a pair of studies detailing the long-term effects of use, a single study demonstrating the benefit among patients in China, and a new guideline update from the ESC focused on cardiomyopathies, which included Class IIa recommendations for mavacamten.

“The new long-term data presented at ESC were consistent with the primary analyses from each study, further underscoring the benefit our first-in-class therapy can provide to patients with symptomatic obstructive HCM,” said Amy Sehnert, MD Vice President, Head of Cardiomyopathy and Heart Failure Clinical Development, Bristol Myers Squibb.1 “These positive data reinforce the clinically meaningful significance of these two Phase 3 trials that led to the approval of CAMZYOS in the United States, the European Union and other countries around the globe. We are excited for the ongoing exploration of the potential of CAMZYOS and remain dedicated to providing support for obstructive HCM patients worldwide.”


  • A double-blind, placebo-controlled, randomized clinical trial with a placebo crossover at 16, VALOR-HCM was designed to assess the efficacy and safety of mavacamten in patients with symptomatic obstructive HCM referred for septal reduction therapy (SRT).2
  • The primary endpoint of interest for the trial was the proportion of patients undergoing SRT, remaining guideline-eligible, or unevaluable SRT status at week 56.2
  • The trial enrolled 112 patients with highly symptomatic obstructive HCM. Of these 108 were considered eligible for the 56-week evaluation.2
  • Results of the trial demonstrated 8.9% of patients in the original mavacamten group and 19.2% of patients in the placebo crossover group met the composite endpoint. In the original mavacamten group, 3 underwent SRT, 1 was SRT eligible, and 1 was not SRT evaluable. In the placebo crossover group, 3 underwent SRT, 4 were SRT eligible, and 3 were not SRT evaluable. Overall, 96 of 108 patients continued mavacamten long term.2


  • A long-term follow-up of patients who completed the EXPLORER-HCM trial. In the ESC Congress 2023 analysis, principal investigator Pablo García-Pavia, MD, PhD, presented a cumulative analysis of the cohort with up to 120 weeks of follow-up.1
  • A cohort of 231 pts enrolled in the EXPLORER cohort of MAVA-LTE. Cohort had a median time on study of 101 weeks at data cut-off. At data cut-off, 215 pts remained on treatment, with a total adjusted exposure of 475 patient-years.1
  • Mavacamten dosing of the 80 patients who reached week 120 were: 2.5 mg (27.5%); 5 mg (31.3%); 10 mg (26.3%); 15 mg (12.5%). From weeks 48 to 120, 14.7% of patients underwent dose adjustments.1
  • Results indicated mavacamten treatment was associated with sustained improvements in mean [SD] change from baseline to week 120 in LVOT gradients (resting, −35.3 [33.0] mmHg; Valsalva, −47.0 [37.3] mmHg), left atrial volume index (−8.5 [10.3] mL/m2) and E/e’ average (−3.9 [5.0]). At week 120, 83.5% of pts had a Valsalva LVOT gradient equal to or greater than 30 mmHg.1

“The presentation of data − the largest and longest analysis of patients on CAMZYOS to-date − illustrates the promise of this game-changing treatment for patients with symptomatic obstructive HCM,” said García-Pavia, who is the head of the Inherited Cardiac Diseases and Heart Failure Unit at the Department of Cardiology of Hospital Universitario Puerta de Hierro.1

Mavacamten in Patients in China

  • Launched to address a lack of evidence of the treatment effect with mavacamten in an Asian population, the EXPLORER-CN trial was designed as a phase 3 randomized, double-blind, placebo-controlled clinical trial of 81 patients from 12 hospitals in China.3
  • For inclusion, patients needed to have obstructive HCM, an LVOT gradient of 50 mmHg or more, and NYHA class II or III symptoms were enrolled and received treatment for 30 weeks. The primary endpoint was change in Valsalva LVOT peak gradient from baseline to week 30.3
  • Valsalva LVOT peak gradient compared to placebo after 30 weeks of treatment (least-squares mean difference, −70.29 mmHg; 95% CI, −89.64 to −50.94; P < .001).3
  • At week 30, the reduction in NT-proBNP was 82% greater (proportion of geometric mean ratio [GMR], 0.18; 95% CI, 0.13 to 0.24) and the reduction in hs-cTnI was 66% greater for the mavacamten group compared with placebo (proportion of GMR, 0.34; 95% CI, 0.27 to 0.42).3

Mavacamten in ESC Guidelines

During ESC Congress 2023, the ESC released the first international guidelines to include all cardiomyopathy subtypes. It is also marked the first time specific recommendations were made for cardiomyopathies other than HCM.4

Included in this new guideline were 2 recommendations for use of mavacamten:

  • Cardiac myosin ATPase inhibitor (Mavacamten), titrated to maximum tolerated dose with echocardiographic surveillance of LVEF, should be considered in addition to a beta-blocker to improve symptoms in adults with resting or provoked left ventricular outflow tract obstruction. (Class IIa, Level A)4
  • Cardiac myosin ATPase inhibitor (Mavacamten), titrated to maximum tolerated dose with echocardiographic surveillance of LVEF, should be considered as monotherapy in symptomatic adults with resting or provoked left ventricular outflow tract obstruction who are intolerant or have contraindications to beta-blockers, verapamil/diltiazem, or disopyramide. (Class IIa, Level B)4

For more on these studies, our editorial team sat down with Milind Desai, MD, MBA, principal investigator of VALOR-HCM, on-site at ESC Congress 2023. Check out the interview below for his perspective on the latest guideline update, the significance of including mavacamten in recommendations, and how ESC data complements our understanding of mavacamten in obstructive HCM.

Relevant disclosures for Desai include Bristol Myers Squibb, Cytokinetics, Tenaya, and others.


  1. Bristol Myers Squibb. Long-term follow-up data from two phase 3 studies of CAMZYOS® (mavacamten) demonstrate consistent and durable response in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). News. August 28, 2023. Accessed August 29, 2023.
  2. Desai MY, Owens A, Wolski K, et al. Mavacamten in Patients With Hypertrophic Cardiomyopathy Referred for Septal Reduction: Week 56 Results From the VALOR-HCM Randomized Clinical Trial. JAMA Cardiol. Published online August 28, 2023. doi:10.1001/jamacardio.2023.3342
  3. Tian Z, Li L, Li X, et al. Effect of Mavacamten on Chinese Patients With Symptomatic Obstructive Hypertrophic Cardiomyopathy: The EXPLORER-CN Randomized Clinical Trial. JAMA Cardiol. Published online August 28, 2023. doi:10.1001/jamacardio.2023.3030
  4. Arbelo E, Protonotarios A, Gimeno JR, et al. 2023 ESC Guidelines for the management of cardiomyopathies [published online ahead of print, 2023 Aug 25]. Eur Heart J. 2023;ehad194. doi:10.1093/eurheartj/ehad194