Cytokinetics Announces Start of ACACIA-HCM, a Pivotal Phase 3 Clinical Trial of Aficamten in Patients With Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy - Seite 2

ACACIA-HCM is expected to enroll 420 patients, randomized on a 1:1 basis to receive aficamten or placebo. Randomization will be stratified by persistent atrial fibrillation and presence of intracavitary obstruction. At screening, patients enrolled in ACACIA-HCM must have a resting left ventricular outflow tract gradient (LVOT-G) < 30 mmHg and post-Valsalva LVOT-G < 50 mmHg in addition to left ventricular ejection fraction (LVEF) ≥ 60%, respiratory exchange ratio (RER) ≥ 1.00 and peak VO₂ ≤ 90% predicted, NT-proBNP ≥ 300 pg/mL or ≥ 900 pg/mL if atrial fibrillation or atrial flutter are present at screening, NYHA functional class II or III and KCCQ Clinical Summary Score ≥ 30 and ≤ 85.

ACACIA-HCM will consist of two parts, with Part 1 comprising Day 1 to Week 36 and Part 2 comprising Week 36 to Week 72. All participants will complete Part 1. At the end of Part 1, participants will continue into Part 2 until the last randomized participant has completed Part 1. Each patient will receive up to four escalating doses of aficamten or placebo based on echocardiographic guidance. Patients 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 an LVEF ≥ 60%. Patients who do not meet escalation criteria will continue to receive their current dose or may be down-titrated if their LVEF is < 50%. Patients who complete ACACIA-HCM will be eligible to participate in an open-label extension clinical trial. Additional information can be found on www.clinicaltrials.gov.

About Aficamten and the Broad Phase 3 Clinical Trials Program

Aficamten is an investigational selective, small molecule cardiac myosin inhibitor discovered following an extensive chemical optimization program that was conducted with careful attention to therapeutic index and pharmacokinetic properties and as may translate into next-in-class potential in clinical development. Aficamten was designed to reduce the number of active actin-myosin cross bridges during each cardiac cycle and consequently suppress the myocardial hypercontractility that is associated with hypertrophic cardiomyopathy (HCM). In preclinical models, aficamten reduced myocardial contractility by binding directly to cardiac myosin at a distinct and selective allosteric binding site, thereby preventing myosin from entering a force producing state.