An open-label extension study of aficamten for Chinese patients with symptomatic obstructive hypertrophic cardiomyopathy: 48-week results

Introduction

While the investigational oral, selective cardiac myosin inhibitor, aficamten, has demonstrated efficacy and safety in a global phase 3 study in patients with symptomatic obstructive hypertrophic cardiomyopathy (oHCM), longer-term clinical data in regional sub-populations are warranted. Herein, we report the 48-week results from an open-label study evaluating the long-term safety and efficacy of aficamten in Chinese oHCM patients.

Methods

Chinese oHCM patients who completed 24 weeks treatment in SEQUOIA-HCM and with baseline left ventricular ejection fraction (LVEF) ≥55%, were eligible. All patients underwent echocardiography-guided dose titration of oral aficamten from 5 to 20 mg daily every two weeks in the first 6 weeks, similar to that of the global phase 3 study. During the dose maintenance period, patients were monitored by echocardiography every 12 weeks through week 48. Primary endpoints included adverse events (AEs) and incidence of LVEF <50% and <40%. Secondary and other endpoints included changes from baseline to week 48 in left ventricular outflow tract gradient (LVOT-G), New York Heart Association (NYHA) Functional Class, Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS), and N terminal pro-B-type natriuretic peptide (NT-proBNP).

Results

All 40 enrolled patients (baseline mean age 52.7 years, 70.0% men, 95.0% in NYHA Class II or III) completed 48 weeks of treatment, 87.5% reaching the highest available daily doses of 15 mg and 20 mg during the study period. No serious AEs or severe treatment emergent AEs (TEAEs) were reported, with 1 (2.5%) participant requiring dose reduction due to mild/moderate TEAEs. LVEF remained ≥50% in all patients throughout the study (Figure D). Change from baseline to week 48 in LVOT-G demonstrated mean (SD) reductions of 45.6 (61.9) mmHg (P<0.001) and 40.3 (48.8) mmHg (P<0.001), with Valsalva and at rest, respectively (Figure A and B). The mean (SD) KCCQ-CSS improved by 8.3 (9.3) points (P<0.001) from a baseline of 83.5 (13.0) points (Figure C). NYHA improved ≥1 class in 15% patients (P=0.024) and no worsening occurred. The mean (SD) percentage reduction in NT-proBNP was 59.2 (33.7) (P<0.001).

Conclusion

Aficamten treatment using a global, individually titrated, dosing strategy in Chinese oHCM patients was well tolerated and resulted in substantial improvements in hemodynamics, symptoms, and quality of life for up to 48 weeks. Similar to global experiences, the majority of Chinese patients ultimately achieved the highest doses available with no low LVEF events or dose interruptions.

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