Dados do Trabalho

Título

Long-term effects of mavacamten (MAVA) treatment in obstructive hypertrophic cardiomyopathy (HCM): updated cumulative analysis of the EXPLORER cohort of MAVA-long-term extension (LTE) study up to 120 weeks (wks)

Introdução e/ou Fundamento

MAVA was efficacious and well tolerated in patients (pts) with obstructive HCM over a median follow-up of 62wks in a previous interim analysis of the ongoing MAVA-LTE study (NCT03723655).

Objetivo

We report an updated cumulative analysis of the EXPLORER cohort of MAVA-LTE up to 120wks.

Materiais e Métodos

Pts who completed EXPLORER-HCM could enroll in MAVA-LTE. All pts initiated the study with MAVA 5mg/day per protocol; dose adjustments to 2.5, 10, or 15mg were based on site-read Valsalva left ventricular outflow tract (LVOT) gradient and LV ejection fraction (LVEF).

Resultados

In total, 231 pts (median age, 61yrs) enrolled in the EXPLORER cohort of MAVA-LTE. Median time on study was 101wks at data cut-off (May 31, 2022) with variations due to differences in enrollment timing. At data cut-off, 215 pts remained on treatment (total adjusted exposure: 475pt-yrs). MAVA dosing of pts who reached wk 120 (n=80) was: 2.5mg (27.5%); 5mg (31.3%); 10mg (26.3%); 15mg (12.5%). Between wks 48–120, 34 of 231 (14.7%) pts underwent dose adjustments. MAVA treatment showed sustained improvements in mean [SD] change from baseline to wk 120 in LVOT gradients (resting, −35.3 [33.0]mmHg; Valsalva, −47.0 [37.3]mmHg), left atrial volume index (−8.5 [10.3]mL/m2) and E/e' mean (−3.9 [5.0]) (Table). At wk 120, 83.5% of pts had a Valsalva LVOT gradient ≤30Mmhg. MAVA was associated with sustained reduction from baseline to wk 120 in N-terminal pro B-type natriuretic peptide (NT-proBNP) level (Table); 75.9% of pts improved by ≥1 class New York Heart Association (Figure). Mean (SD) LVEF decreased by 9.1% (7.1) from baseline to wk 120 but remained in the normal range. Since the previous interim analysis (data cut-off: August 31, 2021), 1 additional transient reduction in LVEF <50% occurred resulting in temporary treatment interruption (a total of 13 pts [5.6%] experienced LVEF <50% from study initiation). The pt resumed treatment at a lower dose 4wks after the event. In total, 74 serious adverse events (SAE) were reported in 47pts (20.3%), with 18 new SAEs and 13 additional pts (5.6%) with SAEs since the previous interim analysis, including 1 new SAE (atrial fibrillation) considered drug-related. No new safety signals. One additional death (leading to a total of 4) occurred due to intracranial hemorrhage. Like the previous 3 deaths (due to acute myocardial infarction, cardiac arrest, and bacterial endocarditis) the event was considered unrelated to the drug study.

Conclusões

MAVA treatment up to 120wks showed sustained improvements in LVOT obstruction, symptoms, and NT-proBNP levels in pts with symptomatic obstructive HCM consistent with the findings of the parent study. MAVA treatment continues to be well tolerated with no new safety signals. This abstract was previously presented at the 2023 European Society of Cardiology annual meeting.