Core Insights - Aficamten shows significant improvements in exercise capacity and recovery compared to metoprolol in patients with obstructive hypertrophic cardiomyopathy (oHCM) and demonstrates long-term efficacy and tolerability in non-obstructive hypertrophic cardiomyopathy (nHCM) patients [1][2][6] Group 1: MAPLE-HCM Study Findings - Aficamten demonstrated a statistically significant improvement in peak oxygen uptake (pVO2) with a treatment difference of +2.3 mL/kg/min (p<0.001) compared to metoprolol [3] - Additional analyses revealed improvements in submaximal exercise performance, including anaerobic threshold (+76 mL, p<0.001) and aerobic efficiency (+0.8 mL/min/watt, p=0.004) [4][5] - Aficamten also improved post-exercise recovery metrics, with a faster VO2 recovery rate compared to metoprolol [3] Group 2: FOREST-HCM Study Findings - In the FOREST-HCM study, 79% of patients with nHCM improved by at least one NYHA Functional Class after 96 weeks of treatment, with 74% becoming asymptomatic [7] - Aficamten led to a mean increase of 11.2 points in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) [7] - Cardiac biomarkers such as NT-proBNP and high-sensitivity cardiac troponin I showed significant declines by Week 12 and remained low through Week 96 [7] Group 3: Aficamten Overview - Aficamten is a selective cardiac myosin inhibitor designed to reduce myocardial hypercontractility associated with hypertrophic cardiomyopathy (HCM) [9] - The drug is currently under evaluation in multiple clinical trials, including ACACIA-HCM for nHCM and CEDAR-HCM for pediatric patients with oHCM [11] - Aficamten has received Breakthrough Therapy Designation from the FDA for symptomatic HCM and is undergoing regulatory review in the U.S., Europe, and China [13]

Core Insights - The primary results from the MAPLE-HCM trial indicate that aficamten demonstrates superiority over the standard-of-care beta-blocker metoprolol in improving exercise capacity in patients with obstructive hypertrophic cardiomyopathy (oHCM) [1][2][3] Company Overview - Cytokinetics is a biopharmaceutical company focused on developing treatments for cardiac muscle dysfunction, with aficamten being a key investigational drug currently under regulatory review in the U.S. and Europe [17][14] - Aficamten is a selective cardiac myosin inhibitor designed to reduce myocardial hypercontractility associated with hypertrophic cardiomyopathy (HCM) [11][12] Clinical Trial Details - The MAPLE-HCM trial is a Phase 3 randomized, double-blind study that enrolled 175 patients, comparing aficamten to metoprolol [2][4] - The primary endpoint was the mean change in peak oxygen uptake (pVO2) after 24 weeks, showing a significant improvement with aficamten (+1.1 mL/kg/min) compared to a decline with metoprolol (-1.2 mL/kg/min) [4][6] Efficacy Results - Aficamten showed a statistically significant least-squares mean difference of 2.3 mL/kg/min in pVO2 compared to metoprolol (p<0.0001) [4][6] - Aficamten also outperformed metoprolol in five of six secondary endpoints, including improvements in functional class and symptom burden [7][8] Safety Profile - The rate of adverse events was similar between aficamten and metoprolol, with aficamten showing a lower rate of treatment discontinuation due to adverse events [9] - Notably, hypertension was more common in the aficamten group, while dizziness was more prevalent in the metoprolol group [9] Regulatory Status - Aficamten is currently under review by the FDA with a target action date of December 26, 2025, and is also being evaluated by the European Medicines Agency [14][12]