Table of Contents

• Trial overview
• Conditions and patient groups
• Trial phases and study designs
• Outcomes being measured
• Key trials of Aficamten
• What the results aim to show

Trial overview

The available studies are testing Aficamten in people with hypertrophic cardiomyopathy, a condition where the heart muscle is thicker than normal.^[1] The trials are looking at both symptom improvement and safety in adults and children.^[1][2]

These studies include completed and authorised trials, so the research is at different stages.^[1][2][3][4]

Conditions and patient groups

One trial studied adults with symptomatic obstructive hypertrophic cardiomyopathy, which means the thickened heart muscle was causing symptoms and also blocking blood flow out of the heart.^[1] Another trial studied adults with symptomatic non-obstructive hypertrophic cardiomyopathy, where there is no major blockage of blood flow out of the heart.^[3]

There is also an authorised study in a pediatric population, which means children, with symptomatic obstructive hypertrophic cardiomyopathy.^[4] The extension study includes adults with symptomatic hypertrophic cardiomyopathy more broadly.^[2]

Trial phases and study designs

The trials include Phase 2, Phase 3, and Phase 4 research.^{[1][2][3][4] Phase 2 and Phase 3 studies usually focus on how well a treatment works and how safe it is, while Phase 4 studies often continue to monitor safety after earlier testing.[2][4]}

All four trials are interventional, which means the researchers give a study treatment and then measure the results.^{[1][2][3][4] Some studies compare Aficamten with placebo, and one compares it with metoprolol succinate.[1][3]}

Outcomes being measured

The trials measure exercise capacity, which shows how well a person can exercise before symptoms limit them.^{[1][3] One study uses peak oxygen uptake measured by cardiopulmonary exercise testing, a test that checks how the heart, lungs, and muscles work during exercise.[1][3]}

Another study measures KCCQ-CSS, a questionnaire score that reflects symptoms and daily life impact.^[3] The pediatric study measures change in Valsalva LVOT-G, a pressure measurement linked to blood flow blockage, and it also tracks adverse events and serious adverse events.^[4]

The extension study tracks adverse events, serious adverse events, and cases where left ventricular ejection fraction falls below 50%, which is a measure of how much blood the heart pumps out with each beat.^[2]

Key trials of Aficamten

NCT05767346 is a Phase 3 study in 170 adults with symptomatic obstructive hypertrophic cardiomyopathy.^[1] It compares Aficamten with metoprolol succinate and looks at change in peak oxygen uptake from baseline to Week 24.^[1]

NCT06081894 is a Phase 3 study in 435 adults with symptomatic non-obstructive hypertrophic cardiomyopathy.^[3] It compares Aficamten with placebo and measures changes in KCCQ-CSS and peak oxygen uptake by Week 36.^[3]

NCT04848506 is an authorised Phase 2 open-label extension study in 896 adults with symptomatic hypertrophic cardiomyopathy.^[2] Its main goal is to assess long-term safety and tolerability by tracking adverse events, serious adverse events, and low LVEF.^[2]

NCT06412666 is an authorised Phase 4 study in 60 children with symptomatic obstructive hypertrophic cardiomyopathy.^[4] It compares Aficamten with placebo and measures change in Valsalva LVOT-G at Week 12, along with safety outcomes through the end of the study.^[4]

What the results aim to show

Across these trials, the main question is whether Aficamten can improve symptoms, exercise ability, and heart-related test results in people with hypertrophic cardiomyopathy.^[1][3][4]

The studies also aim to show whether the treatment can be used safely over time in both adults and children.^[2][4]