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 were randomized 1:1 to aficamten or placebo, with Japanese cohort excluded from primary analysis and dose titration based on echocardiographic guidance.

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

• Study included titration, washout, and end-of-treatment periods, with participants continuing treatment up to 72 weeks for additional secondary and exploratory endpoints, including time to first cardiovascular event.

• Full results will be presented at upcoming medical meetings, with ESC in August as a potential venue.

Efficacy results

• Statistically significant and clinically meaningful improvements were observed in both KCCQ clinical summary score and peak VO2 at week 36 versus placebo (least-squares mean difference 3.0, P=0.021 for KCCQ; 0.67 mL/kg/min, P=0.003 for peak VO2).

• Improvements in KCCQ and peak VO2 were robust, consistent, and similar in magnitude to prior aficamten studies, with scores returning to placebo levels after washout.

• Statistically significant improvements were also seen in key secondary endpoints, including NYHA class, composite Z-score, ventilatory efficiency, and NT-proBNP.

• The treatment effect was rapid in onset, sustained throughout the trial, and reversed upon discontinuation.

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

Safety and tolerability

• No new safety signals were identified; completion rates for planned dosing 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 with LVEF <50%.

• Treatment interruptions due to LVEF <40% occurred in 3% of aficamten patients; most recovered ejection fraction within a week and resumed therapy at lower dose.

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

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