Cytokinetics (CYTK) Study result summary

Study design and methodology

• ACACIA-HCM was a phase III, multi-center, randomized, double-blind, placebo-controlled trial evaluating aficamten in symptomatic non-obstructive HCM patients, with dose escalation based on echocardiography from 5 to 20 mg every two weeks.

• 516 participants outside Japan were randomized 1:1 to aficamten or placebo, with a Japanese cohort continuing separately for local approval and excluded from primary analysis.

• Dual primary endpoints were change in KCCQ clinical summary score (KCCQ-CSS) and peak VO2 from baseline to week 36; secondary endpoints included NYHA class improvement, composite Z-score, NT-proBNP, and left atrial volume index.

• The study included titration, washout, and end-of-treatment periods, with efficacy measured at week 36 and continued treatment up to 72 weeks for additional analyses, including time to first cardiovascular event.

• Full results and subgroup analyses will be presented at upcoming medical meetings.

Efficacy results

• Statistically significant and clinically meaningful improvements were observed in both KCCQ-CSS (LS mean difference 3.0, p=0.021) and peak VO2 (LS mean difference 0.67 ml/kg/min, p=0.003) at week 36 versus placebo.

• KCCQ-CSS improvement was robust and consistent throughout the treatment period, with scores returning to placebo levels after washout.

• Key secondary endpoints, including NYHA class improvement, composite Z-score, ventilatory efficiency, and NT-proBNP, showed statistically significant benefits.

• The magnitude and consistency of KCCQ improvements were similar to prior aficamten studies (SEQUOIA-HCM, REDWOOD-HCM, FOREST-HCM).

• Consistent positive findings were observed across multiple patient-reported and physician-assessed endpoints.

Safety and tolerability

• No new safety signals were identified; completion rates were similar between aficamten (88.4%) and placebo (90.3%).

• LVEF <50% occurred in 10% of aficamten and 1% of placebo patients; 2 aficamten patients had serious heart failure events, and 3% had treatment interruptions due to LVEF <40%.

• Most LVEF reductions were asymptomatic and managed by dose adjustment, with rapid recovery after interruptions.

• MYQORZO (aficamten) carries a boxed warning for risk of heart failure due to systolic dysfunction, requiring REMS program enrollment.

• Safety profile was consistent with prior studies, and most patients transitioned to open-label extension for long-term follow-up.