Trial results for a Phase 3 study evaluating Aficamten compared to metoprolol succinate in adults with symptomatic obstructive hypertrophic cardiomyopathy (oHCM) were posted on ClinicalTrials.gov on 2026-06-09. The study demonstrated that Aficamten led to a significantly greater improvement in peak oxygen uptake compared to metoprolol, with a least squares mean difference of 2.3 mL/kg/min (p=0.0001).
Background
The study investigated Aficamten (CK-3773274) for adults with symptomatic obstructive hypertrophic cardiomyopathy (oHCM) and left ventricular outflow tract obstruction. The trial aimed to compare the efficacy and safety of Aficamten against metoprolol succinate, a beta-blocker commonly used in cardiac conditions, in this patient population.
Trial design
The Phase 3 study (NCT05767346) enrolled 175 adult participants with symptomatic obstructive hypertrophic cardiomyopathy (oHCM). The trial's purpose was to compare the efficacy and safety of Aficamten (CK-3773274) against metoprolol succinate. Participants received either Aficamten (5 mg, 10 mg, 15 mg, or 20 mg) or metoprolol succinate (50 mg, 100 mg, 150 mg, or 200 mg), with corresponding placebos to maintain blinding. Key outcomes evaluated included changes in peak oxygen uptake (pVO2), New York Heart Association (NYHA) functional class, Kansas City Cardiomyopathy Questionnaire - Clinical Summary Score (KCCQ-CSS), Left Ventricular Mass Index (LVMI), Left Atrial Volume Index (LAVI), and N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP).
Key results
The trial results demonstrated several significant improvements for Aficamten compared to metoprolol:
- Change in Peak Oxygen Uptake (pVO2) by Cardiopulmonary Exercise Testing (CPET):
- The mean change for the Aficamten group was 1.07 mL/kg/min (Standard Deviation: 2.767), while the Metoprolol group showed a mean change of -1.24 mL/kg/min (Standard Deviation: 2.186).
- An ANCOVA analysis showed a Least Squares Mean Difference of 2.3 (95% Confidence Interval: 1.52, 3.07) with a p-value of 0.0001, favoring Aficamten.
- Proportion of Patients With ≥1 Class Improvement in New York Heart Association (NYHA) Functional Class:
- 45 participants in the Aficamten group achieved at least one class improvement, compared to 23 participants in the Metoprolol group.
- The Common Rate Difference was 24.8 (95% Confidence Interval: 10.9, 38.7), indicating a higher proportion of improvement with Aficamten.
- Change in Kansas City Cardiomyopathy Questionnaire - Clinical Summary Score (KCCQ-CSS):
- The Least Squares Mean for the Aficamten group was 15.3 points on a scale (Standard Error: 1.56), versus 8.3 points on a scale (Standard Error: 1.57) for the Metoprolol group.
- Mixed Models Analysis yielded a Least Squares Mean Difference of 6.9 (95% Confidence Interval: 2.6, 11.3) with a p-value of 0.002, favoring Aficamten.
- Change in Left Atrial Volume Index (LAVI):
- The Least Squares Mean change for Aficamten was -3.87 mL/m^2 (Standard Error: 0.785), while Metoprolol showed a change of 3.12 mL/m^2 (Standard Error: 0.789).
- Mixed Models Analysis indicated a Least Squares Mean Difference of -6.99 (95% Confidence Interval: -9.14, -4.85) with a p-value of 0.0001, suggesting a reduction with Aficamten.
- Change From Baseline Values in N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP):
- The Geometric Least Squares Mean ratio for Aficamten was 0.26, compared to 1.38 for Metoprolol.
- Mixed Models Analysis showed a p-value of 0.0001.
- Change in Left Ventricular Mass Index (LVMI):
- The Least Squares Mean change for Aficamten was -9.19 g/m^2 (Standard Error: 2.492), versus -4.34 g/m^2 (Standard Error: 2.486) for Metoprolol.
- Mixed Models Analysis showed a Least Squares Mean Difference of -4.86 (95% Confidence Interval: -11.7, 1.98) with a p-value of 0.163.
What this means
The results from this Phase 3 trial indicate that Aficamten offers significant clinical benefits over metoprolol succinate for adults with symptomatic obstructive hypertrophic cardiomyopathy. The superior improvement in peak oxygen uptake, a key measure of exercise capacity, along with a higher proportion of patients achieving NYHA functional class improvement and better KCCQ-CSS scores, suggests that Aficamten could provide a more effective treatment option for improving patient symptoms and quality of life. Furthermore, the observed reductions in Left Atrial Volume Index and NT-proBNP levels with Aficamten point towards favorable effects on cardiac remodeling and reduced cardiac stress, which are important long-term outcomes in oHCM management. While the change in Left Ventricular Mass Index did not reach statistical significance compared to metoprolol, the overall profile of efficacy across multiple endpoints is robust.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for the study NCT05767346, titled "Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Metoprolol Succinate in Adults With Symptomatic oHCM", were posted on 2026-06-09 on clinicaltrials.gov.