Commencement of CEDAR-HCM, a clinical trial of aficamten in a pediatric population with symptomatic obstructive hypertrophic cardiomyopathy

Aficamten is a next-in-class cardiac myosin inhibitor in development for the potential treatment of HCM.

“We are pleased to further expand the broad development program for aficamten with the start of CEDAR-HCM, a trial assessing the safety and efficacy of a cardiac myosin inhibitor in a pediatric population,” said Fady I. Malik, M.D., Ph.D., Cytokinetics’ Executive Vice President of Research & Development. “As a genetic disease, HCM often casts a shadow over entire families, including adolescents and children where it is associated with a high risk of heart failure and serious arrhythmias. HCM can present similarly in adolescents and children as it does in adults and may negatively impact overall quality of life. By evaluating the efficacy and safety of aficamten in another very important group of people, our aim is to provide all members of families impacted by HCM with a potential new treatment option.”

CEDAR-HCM: Clinical Trial Design: CEDAR-HCM is a multi-center, randomized, double-blind, placebo-controlled and open-label extension clinical trial to evaluate the efficacy, pharmacokinetics (PK) and safety of aficamten in a pediatric population with symptomatic obstructive HCM. The primary endpoint is the change in Valsalva left ventricular outflow tract gradient (LVOT-G) from baseline to Week 12. Secondary endpoints include the change from baseline to Week 12 in resting LVOT-G, New York Heart Association (NYHA) Functional Class, pharmacokinetics and cardiac biomarkers including NT-proBNP and hs-cTnI.

CEDAR-HCM is expected to enroll two cohorts, beginning with an initial cohort of approximately 40 adolescent patients aged 12 to 17. Adolescent patients enrolled in CEDAR-HCM must have LVEF greater than 60%, Valsalva LVOT-G greater than 50 mmHg and NYHA Functional Class greater than II. Patients will be randomized on a 2:1 basis to receive aficamten or placebo, and those receiving aficamten will begin with 5 mg dosed once daily. At weeks 2, 4 and 6 patients will receive an echocardiogram to determine if they will be up-titrated to escalating doses of 10, 15 or 20 mg. Dose escalation will occur only if a patient has a Valsalva LVOT-G greater than 30 mmHg and an LVEF greater than 55%. Safety, efficacy and PK data obtained from at least 20 adolescent patients who have completed 12 weeks of double-blind treatment will support the decision to open enrollment in a second cohort of approximately 8 to 10 younger patients (aged 6 to 11). The protocol will be amended to include eligibility criteria and dose selection for the younger pediatric cohort. After 12 weeks of double-blind treatment, eligible patients will rollover into the open label extension period of CEDAR-HCM. Additional information can be found on www.clinicaltrials.gov.

About the Broad Phase III Clinical Trials Program for Aficamten: The development program for aficamten is assessing its potential as a treatment that improves exercise capacity and relieves symptoms in patients with HCM as well as its potential long-term effects on cardiac structure and function. i. SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM), was the pivotal Phase III clinical trial in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). The results from SEQUOIA-HCM show that treatment with aficamten significantly improved exercise capacity compared to placebo, increasing peak oxygen uptake (pVO2) measured by cardiopulmonary exercise testing (CPET) by a least square mean difference (95% CI) of 1.74 (1.04 - 2.44) mL/kg/min (p=0.000002). The treatment effect with aficamten was consistent across all prespecified subgroups reflective of patient baseline characteristics and treatment strategies, including patients receiving or not receiving background beta-blocker therapy. Statistically significant (p<0.0001) and clinically meaningful improvements were also observed in all 10 prespecified secondary endpoints. aficamten was well-tolerated with an adverse event profile comparable to placebo. treatment emergent serious adverse events occurred in 8 (5.6%) and 13 (9.3%) patients on aficamten and placebo, respectively. core echocardiographic left ventricular ejection fraction (lvef) was observed to be><50% in 5 patients (3.5%) on aficamten compared to 1 patient (0.7%) on placebo. there were no instances of worsening heart failure or treatment interruptions due to low lvef. ii. aficamten is also currently being evaluated in maple-hcm, a phase iii clinical trial of aficamten as monotherapy compared to metoprolol as monotherapy in patients with obstructive hcm, iii. acacia-hcm, a phase iii clinical trial of aficamten in patients with non-obstructive hcm, iv. cedar-hcm, a clinical trial of aficamten in a pediatric population with obstructive hcm, and v. forest-hcm, an open label extension clinical study of aficamten in patients with hypertrophic cardiomyopathy (hcm). aficamten received breakthrough therapy designation for the treatment of symptomatic obstructive hcm from the fda as well as the national medical products administration (nmpa) in china.