After years of dedicated research and careful science, Cytokinetics’ aficamten (Myqorzo) is officially FDA approved for obstructive hypertrophic cardiomyopathy, marking the company’s first-ever regulatory approval and ending BMS mavacamten’s reign as the only oHCM treatment.
- Aficamten is a reversible cardiac myosin inhibitor that reduces how hard the heart muscle can contract, which lowers left ventricular outflow tract (LVOT) obstruction.
The FDA’s decision stemmed from the SEQUOIA-HCM trial, which demonstrated aficamten’s efficacy over 24 weeks in symptomatic obstructive HCM patients and found that the drug led to significant benefits.
- Patients on aficamten saw a peak oxygen uptake increase of 1.8 mL/kg/min versus 0.0 mL/kg/min with placebo.
- Nearly 60% of aficamten patients showed improvement in physical activity abilities compared to 24% with placebo.
- The drug was well-tolerated with no cases of worsening HF and lower serious adverse events than placebo (5.6% vs. 9.3%).
Notably, even with these strong results, aficamten comes with the same Risk Evaluation and Mitigation Strategy (REMS) program requirement as mavacamten (e.g. echo monitoring), since both can increase HF risk due to systolic dysfunction.
- That’s because during the trial, LVEF of <50% occurred in 3.5% of aficamten patients versus 0.7% on placebo.
- As a result, aficamten also isn’t recommended for patients with a baseline LVEF of <55%.
- Hypertension (8% vs. 2%) represented the only adverse reaction that occurred in more than 5% of patients, which is common after LVOT obstruction relief.
So what’s the difference between aficamten and mavacamten and why is a second cardiac myosin inhibitor important?
- Aficamten binds away from the myosin’s action site, shifting the enzyme into a super-slow, low-energy state, which reduces how hard heart muscle can contract.
- Meanwhile, mavacamten binds to myosin’s action site, locking it in the “off” form and reducing the number of myosin molecules available for the heart muscle to use.
- Aficamten’s half-life is shorter (3-4 days), allowing for quicker dose changes, while mavacamten’s half-life is longer (6-9 days), requiring longer dose titration (months).
The Takeaway
Cytokinetics’ Fady Malik, MD, PhD, once said that “drug development is a challenging sport” but from the looks of it, aficamten has risen to the task of being the next, and potentially best oHCM drug available.
