Promising results for novel HCM therapy

The investigational therapy EDG-7500 was generally well-tolerated and improved several disease markers in patients with hypertrophic cardiomyopathy (HCM). The safety and efficacy of this agent will be explored further.

EDG-7500 is an investigational cardiac sarcomere modulator tested in the open-label CIRRUS-HCM trial (NCT06347159) in patients with obstructive and non-obstructive HCM [1].

The 17 participants with obstructive HCM received 50 mg (n=8) or 100 mg (n=9) of the agent. In total, 89% of the participants in the 100 mg arm reached a resting left ventricular outflow tract (LVOT) <30 mmHg and 89% achieved Valsalva LVOT <50 mmHg. “These are clinically relevant results,” stated Dr Anjali Owens (University of Pennsylvania, PA, USA). Furthermore, 56% of the participants in the 100 mg arm reached an NT-proBNP <150 pg/mL. Dr Owens mentioned that there were also significant improvements in quality-of-life measurements in the high-dose group.

In participants with non-obstructive disease (n=12), the 100 mg dose (n=5) was associated with quick and robust reductions in NT-proBNP. Although there were numerical improvements in the Kansas City Cardiomyopathy Questionnaire Overall (KCCQ-OSS) and Clinical Summary Score (KCCQ-CSS), these improvements did not reach statistical significance.

“Importantly, we did not see any meaningful reductions in left ventricular ejection fraction (LVEF) or LVEF <50% across a broad exposure range of EDG-7500,” emphasised Dr Owens. This finding is relevant since other cardiac sarcomere modulators have been associated with systolic dysfunction. Finally, there were 4 cases of new-onset atrial fibrillation. “These patients had some underlying conditions, such as hypertension, diabetes, and obstructive lung disease,” said Dr Owens. “Nonetheless, this is a signal we must pay attention to in further studies.”

In conclusion, EDG-7500 displayed the potential to be further investigated as a therapeutic option for patients with obstructive and non-obstructive HCM. The agent was generally well-tolerated and associated with improvements in disease markers.

1. Owens AT, et al. CIRRUS-HCM: a multiple-dose phase 2 study of safety, tolerability, and effects on hemodynamics and functional capacity of the novel cardiac sarcomere modulator EDG-7500 in hypertrophic cardiomyopathy. Hottest trials and trial updates (2), Heart Failure 2025, 17–20 May, Belgrade, Serbia.

Medical writing support was provided by Robert van den Heuvel.
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Posted on 21 May 202517 July 2025