Table 8.

Clinical studies of cardiac myosin activator.

Drug	Study Population	Treatment	Primary and Secondary Endpoints	Main Findings and Conclusions
Danicamtiv [123]	▪HFrEF patients with LV-EF on echocardiography of 40% or lower (N = 40)	Danicamtiv 50, 75, or 100 mg BID or placebo for 7 days	Primary: ▪Safety and tolerability of single and multiple doses. Secondary: ▪Stroke volume, fractional shortening, ejecting time.	▪Danicamtiv increased stroke volume and LA function index. ▪Danicamtiv improved global longitudinal and circumferential strain. ▪Danicamtiv improved LV volume and function.
Omecamtiv (COSMIC-HF trial) [124,125]	▪HFrEF patients with LVEF ≤ 40% ▪NT-proBNP at least 200 pg/mL (N = 448)	Omecamtiv 25 mg BID (fixed-dose), 25 mg BID titrated to 50 mg BID or placebo for 20 weeks	Primary: ▪Changes in cardiac function and ventricular diameter.	▪Omecamtiv improved cardiac function and decreased ventricular diameter. ▪Reduction in HR and NT-proBNP levels with omecamtiv.
			▪Evaluate the effects of omecamtiv on symptoms and HRQoL.	▪Omecamtiv improved HRQoL in HFrEF patients assigned to the pharmacokinetic-titration group.
Omecamtiv (METEORIC-HF trial) [127]	▪HFrEF patients with LVEF < 35% ▪NYHA II–III ▪NT-proBNP level > 200 pg/mL ▪Peak oxygen uptake (Vo2) < 75% (N = 276)	Omecamtiv 25, 37.5, or 50 mg BID or placebo for 20 weeks	Primary: ▪Change in exercise capacity (peak Vo2). Secondary: ▪Total workload. ▪Ventilatory efficiency and daily physical activity	▪No significant difference in the improvement of exercise capacity over 20 weeks.
Omecamtiv (GALACTIC-HF trial) [128,129,130]	▪HFrEF patients with LVEF ≤ 35% ▪NYHA II–IV ▪NT-proBNP level ≥ 400 pg/mL (N = 8256)	Omecamtiv 25, 37.5, or 50 mg BID based on target plasma level or placebo for 20 weeks	Primary: ▪A composite of a first HF event or death from CV causes. Secondary: ▪CV death. ▪Change in TSS ▪First HF hospitalization.	▪No significant difference in the change in TSS between groups. ▪At week 24, the change in NT-proBNP level was 10% lower in the omecamtiv group. ▪Omecamtiv had a lower occurrence of a composite of HF event or death from CV causes.
			▪Evaluate the effect of omecamtiv on baseline EF.	▪Omecamtiv had a greater reduction in HF events in patients who have lower EF at baseline. ▪Omecamtiv produced greater therapeutic benefit as baseline EF decreased.
			▪Evaluate the effect of omecamtiv on NT-proBNP level.	▪Omecamtiv had a greater effect on the primary outcome in patients who had higher NT-proBNP levels at baseline.