Cytokinetics Announces Additional Results From SEQUOIA-HCM Presented in Late Breaking Clinical Trial Session at the European Society of Cardiology Heart Failure 2024 Congress - Seite 2

Titration of patients to their individually determined target dose of aficamten resulted in dose-related increases in plasma drug concentrations with the majority of patients achieving one of the two highest doses (15 mg in 35.0% and 20 mg in 48.6%). Following the completion of dose titration, during the maintenance phase, plasma drug concentrations of aficamten remained stable with low variability for the duration of the treatment.

Overall, there was a low frequency of LVEF <50% in SEQUOIA-HCM. LVEF determined by the core laboratory was the prespecified analysis; 5 patients (3.5%) on aficamten compared to 1 patient (0.7%) on placebo had LVEF <50%. One of the 5 patients on aficamten had LVEF <40% following infection with COVID-19 but did not interrupt treatment as the site-read LVEF remained greater than 40% and the patient did not have symptoms of heart failure due to systolic dysfunction. Overall, there were no instances of worsening heart failure or treatment interruptions due to low LVEF.

To enable same-day dose adjustments, the dosing algorithm in SEQUOIA-HCM used site-interpreted LVEF and LVOT gradients for dose adjustments per protocol as implemented by the interactive Web-response system. There were 7 (4.9%) patients treated with aficamten who underwent per-protocol dose reductions for site-read LVEF <50%. Only one patient treated with aficamten had both core laboratory and site-read LVEF <50%. There were no dose interruptions and none of the patients treated with aficamten experienced symptoms of heart failure due to systolic dysfunction.

“The pharmacological properties that were designed into aficamten appear to translate into the intended clinical benefits. In SEQUOIA-HCM patients underwent dose titration as early as two-weeks and achieved the maximal therapeutic effect in the majority of patients while the occurrence of adverse event was similar to placebo,” said Caroline Coats, M.D., Ph.D., Lead Clinician, West of Scotland Inherited Cardiac Conditions Service, Honorary Senior Lecturer, School of Cardiovascular and Metabolic Health, University of Glasgow. “The favorable safety and tolerability data from SEQUOIA-HCM affirm aficamten as a promising potential treatment for obstructive HCM.”