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Mavacamten in the Real World: Study Demonstrates Safe Reduction in Eligibility for Septal Reduction Therapy

Logistic feasibility supported for treating obstructive HCM under the REMS program

heart showing obstructive cardiomyopathy

Mavacamten, only available through the FDA Risk Evaluation and Mitigation Strategy (REMS) program because of the potential for development of heart failure, demonstrated safety and efficacy in a real-world prospective observational study of 150 patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). The study was published by Cleveland Clinic researchers in Progress in Cardiovascular Diseases (Epub 2024 Feb 13).


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Consistent with clinical trial findings, most patients in this report realized functional gains, improved left ventricular outflow tract (LVOT) gradients and reduced eligibility for septal reduction therapy (SRT) at 12 weeks. Just 2% of patients had temporary drug interruption for left ventricular ejection fraction (LVEF) of less than 50%, and no patients developed LVEF of less than 30% or heart failure requiring hospitalization — results that compared favorably with those from clinical trials of mavacamten, the researchers noted.

“Notably, the logistics of managing mavacamten under the REMS program were successfully addressed, indicating feasibility in general practice,” says the study’s corresponding author, Milind Desai, MD, MBA, Director of the Hypertrophic Cardiomyopathy Center at Cleveland Clinic. “In addition, the low rate of mavacamten interruption in this and other real-world reports indicates that echocardiographic monitoring may not need to be as frequent as suggested by clinical trial data.”

Mavacamten: an important new drug with restrictions

Septal myectomy, the leading form of SRT, is considered the gold standard for treating obstructive HCM. But because of the surgery’s inherent risk and complexity, it should only be performed at experienced tertiary care surgical centers, limiting this option to relatively few patients.

Mavacamten was FDA-approved for symptomatic obstructive HCM in April 2022 after results from phase 3 clinical trials demonstrated improvements in LVOT gradient, symptoms and physical function, as well as reduced SRT eligibility. The novel cardiac myosin inhibitor was the first medication approved for this indication.

However, because the drug also reduces LVEF — increasing risk of heart failure — its use is restricted to availability only through the REMS program. The program requires monitoring for heart failure with periodic echocardiograms, and interruption of the drug for LVEF less than 50% or heart failure symptoms. In addition, because of potentially dangerous interactions with certain cytochrome P450 inhibitors, the REMS also requires screening for drug interactions each time mavacamten is dispensed.

Because of the potential risk of mavacamten use and uncertainty about how well providers can meet the REMS restrictions, obtaining real-world data is especially important. “Our current study reports on a larger and more geographically diverse population with a longer follow-up than other published real-world studies to date,” Dr. Desai notes.

Study design and findings

The study cohort consisted of the first 150 adults who were started on mavacamten 5 mg at Cleveland Clinic facilities in Ohio and Florida for symptomatic obstructive HCM. The patients had a mean age of 65 years, 53% were women, 83% were taking beta-blockers and 61% were in New York Heart Association (NYHA) class III. Patients with LVEF less than 55% at baseline were excluded.

NYHA class, LVEF and LVOT gradients were determined at baseline and at 4, 8 and 12 weeks. Mavacamten dosage was titrated per assessments of symptoms and echocardiography.

Key findings were as follows:

  • Mean Valsalva LVOT gradient was reduced from 72 ± 43 mmHg at baseline to 30 ± 29 mmHg at 12 weeks (P < .001).
  • Mean LVEF was 66.6% at baseline and 62.7% at 12 weeks (P < .0001).
  • At last follow-up (261 ± 143 days [range, 31-571]), 46% of patients achieved an improvement of one NYHA class, 18% achieved an improvement of at least two classes, and the remainder had no change in symptoms.
  • No patients developed LVEF ≤ 30%, required hospital admission for heart failure or underwent SRT.


Lessons from real-world experience

“The improvements we observed mirror those seen in clinical trials,” says Dr. Desai. “But several important differences were also observed that provide important lessons to clinical practice.” He highlights the following:

  • A dedicated program is needed to meet REMS requirements. Key components include patient access to a specialty pharmacy and a plan to perform serial echocardiograms, which may be done either at large centers or at local healthcare facilities.
  • Don’t rush up-titration of mavacamten. The rate of drug interruption due to LVEF reduction was much lower in this study (2%) than in clinical trials. Dr. Desai attributes this to the use of a more conservative approach to mavacamten dose titration. While clinical trials used a protocol-driven automatic strategy starting at 8 weeks, Cleveland Clinic guided titration starting at 12 weeks according to symptoms, LVOT gradients and LVEF, in line with current recommendations.

“Using these practices, it’s possible that echocardiographic monitoring need not be so stringent as recommended based on the clinical trials,” adds study co-author Zoran Popovic, MD, PhD, a cardiologist in Cleveland Clinic’s Section of Cardiovascular Imaging. “Further long-term data to determine if symptomatic improvement and reduction of the need for SRT are sustained will also help inform the use of this important new drug.”


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