New Cytokinetics Drug Approved for Hypertrophic Cardiomyopathy

 The FDA on Friday approved aficamten (Myqorzo) for symptomatic obstructive hypertrophic cardiomyopathy (HCM), drugmaker Cytokinetics announced.

Aficamten is an allosteric and reversible inhibitor of cardiac myosin motor activity that reduces cardiac contractility and left ventricular outflow tract obstruction; the drug is indicated to improve functional capacity and symptoms in adults with the symptomatic obstructive form of HCM, the most common monogenic inherited cardiovascular disorder.

In SEQUOIA-HCM, aficamten improved peak oxygen uptake, meeting the phase III trial's primary endpoint. As compared with baseline, mean change at 24 weeks was 1.8 mL/kg/min with the drug versus no change with placebo (P<0.001).

"HCM is a heart muscle disease associated with a significant symptom burden. This approval of a new drug, Myqorzo, represents a meaningful addition to the treatment options available for symptomatic obstructive HCM patients," investigator Martin Maron, MD, of Lahey Hospital and Medical Center in Burlington, Massachusetts, said in a statement.

"In SEQUOIA-HCM, Myqorzo improved exercise capacity and reduced symptoms while also being well-tolerated. For these reasons, Myqorzo represents an important step forward in how we care for people living with obstructive HCM," Maron added.

Over 300,000 patients in the U.S. have been diagnosed with HCM, approximately half of whom have obstructive disease, according to Cytokinetics. In those cases, the thickening of heart muscle results in narrowing and stiffening of the inside of the left ventricle. Ultimately, the left ventricle is less able to fill with blood, limiting the heart's pumping function and patients' ability to exercise.

Along with the enhanced exercise capacity and reductions in symptoms, secondary analyses of the pivotal trial showed greater improvements in hemodynamic response and cardiac biomarker response. At week 24, 97% of those in the aficamten group had at least one secondary benefit compared with 59% in the placebo group.

Serious adverse events (AEs) in the trial were numerically less frequent in the aficamten arm (5.6% vs 9.3% in the placebo arm). AEs occurring more commonly with aficamten included palpitations (7.0% vs 2.9%, respectively) and hypertension (7.7% vs 2.1%).

Labeling includes a boxed warning, as the drug reduces left ventricular ejection fraction (LVEF) and can cause heart failure due to systolic dysfunction. LVEF assessment via echocardiogram is required prior to and during treatment. Aficamten was approved with a risk evaluation and mitigation strategy (REMS), but drug-drug interaction monitoring is not required.

Aficamten is the second approval for symptomatic obstructive HCM after the cardiac myosin inhibitor mavacamten (Camzyos) gained FDA's blessing in 2022. Mavacamten also has a boxed warning for heart failure risk and carries warnings that drug interactions may lead to heart failure or loss of effectiveness.

There is reason to believe aficamten could be better in terms of the heart failure risk, however, including the drug's faster pharmacodynamic profile that allows for dose adjustments as often as every 2 weeks. The drug comes in film-coated tablets at several dosages (5 mg, 10 mg, 15 mg, and 20 mg) with a recommended starting dose of 5 mg.

Due to the risk for heart failure, starting aficamten is not recommended in patients with an LVEF below 55%. For patients already on treatment, the dosage should be decreased if LVEF drops below 50% but remains at 40% or higher. Treatment should be paused if LVEF drops below 40% or if clinical status worsens.

The drug is contraindicated in patients on rifampin.

https://www.medpagetoday.com/cardiology/chf/119130