The Food and Drug Administration (FDA) has approved Camzyos™ (mavacamten) for the treatment of adults with symptomatic New York Heart Association (NYHA) class II-III obstructive hypertrophic cardiomyopathy (HCM) to improve functional capacity and symptoms.
Camzyos is an oral, selective allosteric and reversible inhibitor of cardiac myosin. It reduces cardiac muscle contractility by inhibiting excessive myosin actin cross-bridge formation and dysregulation that result in hypercontractility, left ventricular hypertrophy and reduced compliance.
The approval was based on data from the randomized, multicenter, double-blind, placebo-controlled, parallel-group phase 3 EXPLORER-HCM trial (ClinicalTrials.gov Identifier: NCT03470545), which assessed the efficacy and safety of mavacamten in 251 adults with symptomatic, obstructive HCM. Patients were randomly assigned 1:1 to receive a starting dose of mavacamten 5mg orally once daily or placebo for 30 weeks. The mavacamten dose was periodically adjusted to optimize patient response (decrease in LVOT gradient with Valsalva maneuver) and maintain LVEF of 50% or greater.
The primary endpoint of the study was the proportion of patients who achieved either improvement of mixed venous oxygen tension (pVO2) by 1.5mL/kg/min or greater plus improvement in NYHA class by at least 1, or improvement of pVO2 by 3.0mL/kg/min or greater, plus no worsening in NYHA class.
Results showed that 37% of patients treated with mavacamten met the primary endpoint at week 30 compared with 17% of patients who received placebo (treatment difference, 19%; 95% CI, 9-30; P =.0005). Additionally, mavacamten was associated with statistically significant and clinically meaningful improvements in the change from baseline through week 30 in the following key secondary endpoints vs placebo, respectively:
- Mean change in post exercise left ventricular outflow tract (LVOT) peak gradient: -47mmHg vs -10mmHg (treatment difference, -35; 95% CI: -43, -28; P <.0001);
- Mean change in pVO2: 1.4mL/kg/min vs -0.1 (treatment difference, 1.4; 95% CI, 0.6-2.1; P <.0006);
- Number (%) of patients with an improvement of at least 1 NYHA class: 80 (65%) vs 40 (31%) (treatment difference, 34%; 95% CI, 22-45; P <.0001);
- Mean change in Kansas City Cardiomyopathy Clinical Summary Score (KCCQ-CSS): 14 vs 4 (treatment difference, 9; 95% CI, 5-13; P <.0001);
- Mean change in HCM Symptom Questionnaire Shortness of Breath Domain Score: -3 vs -1 (treatment difference, -2; 95% CI: -2, -1; P <.0001).
In the mavacamten arm, at the end of the treatment period, 49% of patients were receiving the 5mg dose, 33% were receiving the 10mg dose, and 11% were receiving the 15mg dose.
Camzyos carries a Boxed Warning associated with a risk of heart failure due to systolic dysfunction. Echocardiogram assessments of left ventricular ejection fraction (LVEF) are required prior to and during treatment. Initiation of Camzyos in patients with LVEF less than 55% is not recommended. Due to the risk of heart failure, Camzyos is available only through a restricted program called the Camzyos REMS Program.
The most common adverse events reported with Camzyos were dizziness (27%) and syncope (6%). The drug may also cause fetal toxicity if administered to a pregnant female.
Camzyos is contraindicated with the concomitant use of moderate to strong CYP2C19 inhibitors or strong CYP3A4 inhibitors and moderate to strong CYP2C19 inducers or moderate to strong CYP3A4 inducers. Concomitant use of Camzyos and drugs that interact with these enzymes may lead to life-threatening drug interactions such as heart failure or loss of effectiveness.
Camzyos is supplied as 2.5mg, 5mg, 10mg, and 15mg capsules and is expected to be available by next week.
- U.S. Food and Drug Administration approves Camzyos™ (mavacamten) for the treatment of adults with symptomatic New York Heart Association class II-III obstructive hypertrophic cardiomyopathy (HCM) to improve functional capacity and symptoms. News release. Bristol Myers Squibb. Accessed April 28, 2022. https://www.businesswire.com/news/home/20220428006368/en
- Camzyos. Package insert. Bristol Myers Squibb; 2022. Accessed April 28, 2022. https://packageinserts.bms.com/pi/pi_camzyos.pdf