Aficamten Receives FDA Approval for Obstructive Hypertrophic Cardiomyopathy

Aficamten (Myqorzo; Cytokinetics), an oral selective cardiac myosin inhibitor, has been approved by the FDA for the treatment of patients with obstructive hypertrophic cardiomyopathy (oHCM), according to a news release from Cytokinetics. The FDA had previously extended the review period for aficamten’s new drug application to ensure a full review of the accompanied Risk Evaluation and Mitigation Strategy (REMS).^1,2

"Living with symptomatic obstructive HCM means managing physical limitations and burdensome symptoms every day of your life," said Lisa Salberg, founder and CEO of the Hypertrophic Cardiomyopathy Association, in a news release. "For far too long, we've had few options to address our needs, and the approval of Myqorzo is a long-awaited and major addition to bring new hope to patients living with oHCM."¹

Data from 2 pivotal phase 3 clinical trials provided backing for aficamten’s approval in this population. In MAPLE-HCM (NCT05767346) and SEQUOIA-HCM (NCT05186818), aficamten improved peak oxygen uptake and decreased symptoms of oHCM when compared with either metoprolol succinate (Toprol XL; Melinta Therapeutics) or placebo.^3-7

"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 [patients with] obstructive HCM," said Martin Maron, MD, director of the Hypertrophic Cardiomyopathy Center at Lahey Hospital and Medical Center, and principal investigator of the SEQUOIA-HCM trial, in a news release.¹

MAPLE-HCM

MAPLE-HCM is a phase 3 randomized, double-blind, active-comparator clinical trial comparing aficamten with metoprolol in patients with symptomatic oHCM. Investigators enrolled 175 patients, who were randomly assigned to receive either aficamten 5 to 20 mg daily (n = 88) or metoprolol 50 to 200 mg daily (n = 87).^3,4

At the 24-week cutoff, change in peak oxygen uptake was 1.1 mL/kg of body weight per minute in the aficamten group (95% CI, 0.5-1.7) and –1.2 mL/kg/min in the metoprolol group (95% CI, -1.7 to -0.8) (least-squares mean between-group difference, 2.3 mL/kg/min; 95% CI, 1.5-3.1; P < .001).^3,4

Patients receiving aficamten also reported significant improvements in New York Heart Association functional class (NYHA), Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS), left ventricular outflow tract gradient, N-terminal pro–B-type natriuretic peptide level, and left atrial volume index compared with patients receiving metoprolol. There were no major differences in left ventricular mass index observed between the 2 treatment groups, and the adverse event profile was also similar between each group.³

Differing from SEQUOIA-HCM, MAPLE-HCM included patients with less severe oHCM, allowing for a broader population and more thorough assessment of aficamten’s efficacy across a spectrum of severity.⁴

“In showing that aficamten is superior to metoprolol on all clinically relevant efficacy end points, these results call into question the reliance on β-blockers as the initial treatment modality for obstructive HCM that has prevailed for over 60 years,” Pablo Garcia-Pavia, MD, PhD, a member of the Department of Cardiology at Hospital Universitario Puerta de Hierro and principal investigator in MAPLE-HCM, said in a news release.⁴

SEQUOIA-HCM

SEQUOIA-HCM, conducted prior to MAPLE-HCM, specifically focused on patients with symptomatic HCM and compared aficamten with placebo. In total, 282 patients were randomized to the aficamten (n = 142) or placebo (n = 140) groups, with end points set to be measured at week 24.⁶

At data cutoff, the mean change in peak oxygen uptake was 1.8 mL/kg/min (95% CI, 1.2-2.3) in the aficamten group and 0.0 mL/kg/min (95% CI, -0.5 to 0.5) in the placebo group (least-squares mean between-group difference, 1.7 mL/kg/min; 95% CI, 1.0-2.4; P < .001). Furthermore, patients met all prespecified secondary end points, including exhibiting significant improvement in NYHA functional class and in KCCQ-CSS. Adverse event incidence was similar in each group.⁶

"In SEQOIA-HCM, Myqorzo improved exercise capacity and reduced symptoms while also being well tolerated," Maron said. "For these reasons, Myqorzo represents an important step forward in how we care for people living with obstructive HCM."¹

The results from SEQUOIA-HCM affirm aficamten’s role in symptomatic oHCM, whereas MAPLE-HCM data demonstrate the effectiveness of the agent in patients across the spectrum of severity. Now that aficamten is approved by the FDA, patients with oHCM—a condition that limits the heart’s pumping function and results in reduced exercise capacity and cardiovascular symptoms—will have an effective and safe treatment option to reduce the daily burden of disease.⁴

"I'm pleased that the approved label and [REMS] reflect the distinct characteristics of Myqorzo, including a straightforward, flexible dosing regimen, no requirement for drug-drug interaction monitoring, and a predictable safety profile," said Robert I. Blum, president and CEO of Cytokinetics, in a news release.¹

REFERENCES

1. Cytokinetics announces FDA approval of Myqorzo (aficamten) for the treatment of adults with symptomatic obstructive hypertrophic cardiomyopathy to improve functional capacity and symptoms. News release. Cytokinetics. December 19, 2025. Accessed December 22, 2025. https://ir.cytokinetics.com/press-releases/press-release-details/2025/Cytokinetics-Announces-FDA-Approval-of-MYQORZO-aficamten-for-the-Treatment-of-Adults-with-Symptomatic-Obstructive-Hypertrophic-Cardiomyopathy-to-Improve-Functional-Capacity-and-Symptoms/default.aspx

2. Cytokinetics announces new PDUFA date for aficamten in obstructive hypertrophic cardiomyopathy. News release. Cytokinetics. May 1, 2025. Accessed December 17, 2025. https://ir.cytokinetics.com/press-releases/press-release-details/2025/Cytokinetics-Announces-New-PDUFA-Date-for-Aficamten-in-Obstructive-Hypertrophic-Cardiomyopathy-05-01-2025/default.aspx

3. Garcia-Pavia P, Maron MS, Masri A, et al; MAPLE-HCM Investigators. Aficamten or metoprolol monotherapy for obstructive hypertrophic cardiomyopathy. N Engl J Med. 2025;393(10):949-960. doi:10.1056/NEJMoa2504654

4. Cytokinetics announces primary results from MAPLE-HCM presented at the European Society of Cardiology Congress 2025 and published in the New England Journal of Medicine. News release. Cytokinetics. August 30, 2025. Accessed December 17, 2025. https://ir.cytokinetics.com/press-releases/press-release-details/2025/Cytokinetics-Announces-Primary-Results-from-MAPLE-HCM-Presented-at-the-European-Society-of-Cardiology-Congress-2025-and-Published-in-The-New-England-Journal-Of-Medicine/default.aspx

5. Phase 3 trial to evaluate the efficacy and safety of aficamten compared to metoprolol succinate in adults with symptomatic oHCM (MAPLE-HCM). ClinicalTrials.gov. Updated May 2, 2025. Accessed December 17, 2025. https://clinicaltrials.gov/study/NCT05767346

6. Maron MS, Masri A, Nassif ME, et al; SEQUOIA-HCM Investigators. Aficamten for symptomatic obstructive hypertrophic cardiomyopathy. N Engl J Med. 2024;390(20):1849-1861. doi:10.1056/NEJMoa2401424

7. Aficamten vs placebo in adults with symptomatic obstructive hypertrophic cardiomyopathy (SEQUOIA-HCM). ClinicalTrials.gov. Updated February 27, 2025. Accessed December 17, 2025. https://clinicaltrials.gov/study/NCT05186818