Patients with obstructive hypertrophic cardiomyopathy (oHCM) and mild symptoms treated with aficamten experienced improved clinical outcomes with few serious adverse events, demonstrating results similar to patients with more advanced symptoms, according to an analysis from the SEQUOIA-HCM trial published May 17 in the European Heart Journal.

The main results from SEQUOIA-HCM showed that aficamten, a novel cardiac myosin inhibitor, led to significant improvements in symptom, function and quality of life benefits. In the present substudy, Martin S. Maron, MD, et al., assessed the clinical benefit based on oHCM symptom severity at baseline.

Of 282 patients, 118 (62 randomized to aficamten and 56 to placebo) had mild symptoms (defined as NYHA class II and Kansas City Cardiomyopathy Questionnaire Clinical Summary Score [KCCQ-CSS] ≥80) and 150 (71 randomized to aficamten and 79 to placebo) had moderate to severe symptoms (NYHA class II-IV and KCCQ-CSS <80). Fourteen patients were excluded from this substudy because of missing data for NYHA class or KCCQ-CSS.

Results showed that at 24 weeks, the primary endpoint of change in peak oxygen uptake (pVO2) from baseline increased with aficamten from 19.0 to 20.7 mL/kg/min in the mild symptom group (p=0.003 vs. placebo) and from 17.8 to 19.8 mL/kg/min in the moderate to severe symptom group (p<0.001 vs. placebo). Thus, a similar treatment effect on the primary outcome was observed with a change of 1.6 in the mild group and 1.8 in the moderate to severe group (p=0.83 for interaction).

Furthermore, KCCQ-CSS improved in both groups. However, improvement was greater in the moderate to severe symptom group (10 points vs. 4 points in the mild group [p=0.02 for interaction]). Notably, changes in NYHA class, resting or Valsalva gradients and NT-proBNP were not significantly different between groups. Serious adverse events were rare in both groups.

Maron and colleagues write the findings demonstrate that "...it may be reasonable to consider earlier treatment with aficamten in patients with oHCM, without waiting for the development of marked disability." Looking ahead, they say that "these data support the need for further investigations characterizing the impact of even earlier treatment intervention with aficamten on natural history of disease progression in patients with oHCM."