Positive results from cohort 4 of REDWOOD-HCM study of aficamten in non obstrauctive cardiomyopathy and long term results from FOREST HCM study.-Cytokinetics

Additionally, 48-week data from FOREST-HCM (Follow-up, Open-Label, Research Evaluation of Sustained Treatment with Aficamten in HCM) were also presented at the meeting.

“Patients with non-obstructive HCM have no effective medical therapies and lack an apparent therapeutic target like reducing or eliminating the LVOT obstruction, underscoring the need for a therapy to address the underlying cause of the disease,” said Fady I. Malik, M.D., Ph.D., Cytokinetics’ Executive Vice President of Research & Development. “The results from Cohort 4 of REDWOOD-HCM demonstrate that treatment with aficamten is well-tolerated and associated with significant improvements in heart failure symptoms and cardiac biomarkers in patients with non-obstructive HCM and support the advancement of aficamten into a pivotal Phase III clinical trial in patients with non-obstructive HCM. Additionally, aficamten continues to demonstrate sustained hemodynamic and biomarker improvement after nearly a year of treatment with the majority of oHCM patients becoming either asymptomatic or mildly symptomatic.”

REDWOOD-HCM Cohort 4 : Aficamten Improved Heart Failure Symptoms and Cardiac Biomarkers in Patients with Non-Obstructive HCM. Ahmad Masri, M.D., Director of the Hypertrophic Cardiomyopathy Center at Oregon Health & Science University, presented results from Cohort 4 of REDWOOD-HCM. Cohort 4 enrolled 41 patients with nHCM, who were New York Heart Association (NYHA) Class II/III with left ventricular ejection fraction (LVEF) greater than 60% without a resting or provoked left ventricle outflow tract (LVOT) gradient (<30 mm hg). eligible patients had a nt-probnp ?300 pg ml and no history of lvef><45%. all patients received up to three escalating doses of aficamten, beginning with 5 mg once daily and increasing to 10 and 15 mg once daily guided by echocardiographic assessment of lvef. overall treatment duration was 10 weeks with a 2-week washout period.></45%.></30>

At 10 weeks, patients in Cohort 4 experienced significant improvements in NT-proBNP, with an average decrease of 66% (p<0.0001). high-sensitivity troponin i levels also improved significantly proportional to baseline at each study visit (p><0.05). an improvement of ?1 nyha functional class was observed in 22 of 41 (54%) patients. after the 2-week washout period, nt-probnp and high-sensitivity troponin i levels returned to baseline levels.></0.05).></0.0001).>

Aficamten was generally well-tolerated. By Week 6, 35 (85%) of patients achieved the highest dose of 15 mg of aficamten, and 6 (15%) achieved 10 mg. There were no drug discontinuations due to adverse events. One dose reduction to 10 mg occurred due to fatigue, and one temporary dose interruption occurred due to palpitation. Three patients had serious adverse events, but none were attributed to aficamten. In 27 patients (66%), at least one treatment emergent adverse event was reported. Three patients (7.3%) had LVEF <50% at week 10; all three patients returned to baseline lvef after the 2-week washout period. no adverse events of heart failure were reported.></50%>

FOREST-HCM: Aficamten Well Tolerated with Sustained Treatment Effect Up to 48 Weeks: Sara Saberi, M.D., Assistant Professor of Internal Medicine at the University of Michigan Health Frankel Cardiovascular Center, presented the 48-week data from FOREST-HCM. Previously presented data from FOREST-HCM showed that treatment with aficamten was associated with significant and sustained reductions in LVOT-G, improvements in New York Heart Association (NYHA) Functional Class, improvements in cardiac biomarkers, and improvement in self-reported health status using the Kansas City Cardiomyopathy Questionnaire (KCCQ) through 24 weeks. New data through 48 weeks of treatment showed that aficamten was associated with significant reductions in the average resting LVOT-G (mean change from baseline (SD) = -32 (28) mmHg, p<0.0002) and valsalva lvot-g (mean change from baseline (sd)="-47" (28) mmhg, p><0.0001). treatment with aficamten also resulted in significant improvements in nyha class, with 88% of patients experiencing a greater than 1 nyha functional class improvement, and significant improvements in nt-probnp, with an average decrease of 70% from baseline to week 48 (p><0.0001). at baseline, 19 patients met eligibility criteria for septal reduction therapy (srt), defined as nyha class iii and peak lvot-g greater than 50 mmhg, but treatment with aficamten eliminated srt eligibility in all 19 patients at 48 weeks.></0.0001).></0.0001).></0.0002)>

Aficamten was safe and well-tolerated, with no treatment-related serious adverse events (SAEs). There were no instances of LVEF <50% attributed to aficamten. one dose reduction and one temporary dose interruption occurred, neither of which were attributed to treatment with aficamten.></50%>