The MAPLE-HCM trial demonstrated a statistically significant least-squares mean difference of +2.3 mL/kg/min in peak oxygen uptake (pVO₂) for aficamten versus metoprolol at 24 weeks (p<0.0001). How clinically meaningful is this improvement in exercise capacity for patients with symptomatic obstructive HCM?

Beta-blockers have been the cornerstone of obstructive HCM management for over six decades, yet aficamten demonstrated superior efficacy across nearly all endpoints. Do these results suggest a potential paradigm shift in first-line treatment strategies for oHCM?

More than half (51%) of aficamten-treated patients experienced an improvement of at least one NYHA functional class, compared to 26% on metoprolol (p<0.001). How impactful is this degree of functional improvement when considering day-to-day patient outcomes?

Aficamten led to an 81% reduction in NT-proBNP levels and significant improvements in left atrial volume index, suggesting potential benefits on cardiac remodeling and diastolic dysfunction. How do these findings translate into long-term risk modification for patients with obstructive HCM?

Despite demonstrating strong hemodynamic effects, aficamten showed similar rates of adverse events compared to metoprolol, with only 4.5% requiring dose down-titration versus nearly 30% on metoprolol. How do these safety outcomes affect your confidence in using aficamten broadly in clinical practice?

The primary endpoint benefit was consistent across all prespecified subgroups, including newly diagnosed and treatment-naïve patients. Does this suggest aficamten could be considered earlier in the treatment algorithm, even before beta-blockers in some cases?

With the FDA currently reviewing the NDA for aficamten and a PDUFA target action date of December 26, 2025, what are your expectations for regulatory approval, and how could this approval reshape the competitive treatment landscape for obstructive HCM?

Beyond MAPLE-HCM and SEQUOIA-HCM, aficamten is also being evaluated in trials for non-obstructive HCM, pediatric oHCM, and open-label extension studies. How might these ongoing programs expand its clinical relevance and position aficamten as a cornerstone therapy across the entire HCM spectrum?