Phase 2 study with cardiac myosin inhibitor in non-obstructive HCM

ESC Heart Failure 2023 A phase 2, open-label, dose finding study evaluated the safety and efficacy of aficamten in patients with non-obstructive HCM.

Presented at the ESC Heart Failure 2023 by: Ahmad Masri, MD- Portland, OR, USA

Introduction and methods

Aficamten is a cardiac myosin inhibitor targeting myocardial hypercontractility and impaired relaxation. An phase 2, open label, dose finding study evaluated the safety and efficacy of aficamten in patients with non-obstructive HCM.

A total of 41 patients (mean age 56 years, 59% female) with symptomatic non-obstructive HCM (NYHA class II/III, LVEF ≥ 60%, NT-proBNP >300 pg/mL) entered the study. Patients received 10 weeks of treatment, followed by 4 weeks of wash-out. Available doses were 5, 10, 15 mg. Doses were up-titrated if LVEF ≥55%, maintained if LVEF 50-54%, down-titrated if LVEF<50% and discontinued if LVEF <40%.

Main results

• 85% of patients (n=35) achieved the highest dose of 15 mg and 15% of patients (n=6) achieved 10 mg of aficamten at week 6.
• A reversible decrease in LVEF of -5.5% was observed from baseline to week 10.
• No patients experienced LVEF< 40%. 3 patients had LVEF <50% at week 10. The LVEF of all patients recovered to normal during the 2-week wash-out period and there were no related SAEs.
• SAEs, including one death, occurred in 4 patients. None were attributed to the study drug.
• The mean change from baseline to week 10 in KCCQ-CSS was +10.6 points.
• 12.5% of patients reported a small improvement in symptom burden at week 10 (≥5-10 points in KCCQ-CSS), 20% a moderate to large improvement (≥10-20 points), 25% a large to very large improvement (≥20 points), 7.5% experienced worsening of symptoms (≤ -5 points) and 35% experienced no change in clinical symptoms (>-5 to <5 points).
• 56% of patients had a functional improvement of ≥1 NYHA class and 28% of patients were asymptomatic (NYHA class I) at week 10.
• Among patients with angina at baseline (n=14), the SAQ-AF Score improved by 14.3 points at week 10.
• At week 10, the mean relative reduction in high-sensitivity cardiac troponin was 21% (absolute reduction -24.8 ng, SE 11.6) and 55% in NT-proBNP (absolute reduction -870 pg/mL, SE 155.3).

Conclusion

This phase 2, open-label, dose finding study showed that aficamten was generally well tolerated in patients with non-obstructive HCM. A modest reduction of -5.5% LVEF was observed by week 10, which was rapidly reversed during the wash-out period. The majority of patients reported improvement of symptoms. Aficamten will be further investigated in patients with non-obstructive HCM in a phase 3 study.

• Our reporting is based on the information provided at the ESC Heart Failure -