Author + information
- Stephen B. Heitner,
- Daniel Jacoby,
- Steven J. Lester,
- Andrew Wang,
- David Zhang and
- Amy Sehnert
In PIONEER-HCM, patients with symptomatic obstructive hypertrophic cardiomyopathy (oHCM) showed improvements in left ventricular outflow tract (LVOT) obstruction, exercise capacity, and symptoms after 12 weeks treatment with mavacamten (MAVA). To examine the long-term safety and effectiveness of MAVA, an open-label extension study, PIONEER-OLE was initiated.
PIONEER-OLE (NCT03496168) is a two-year trial for patients who completed PIONEER-HCM (NCT02842242). Starting dose of MAVA is 5 mg per day followed by adjustment at Week 6 to an individualized therapeutic dose (5, 10, or 15 mg). Evaluations occur at Wks 0, 4, 8, and 12 and every 12 wks thereafter to monitor LV ejection fraction (LVEF), LVOT gradient, NYHA Class, NT-proBNP, drug concentration, and safety.
Twelve patients (mean age, 57 y; 11 on beta-blockers) began dosing from MAY – SEP, 2018. Analysis for 7 of 12 patients reaching at least 12 wks are shown (Table). Mean baseline LVOT obstruction and LVEF were similar to PIONEER-HCM. MAVA significantly reduced resting and provoked LVOT gradients within-subject at wk 12 compared to baseline (p=0.016 and p=0.031, respectively). Of 6 patients with NYHA Class at wk 12, 3 improved (Class II to I) and 3 remained Class II. MAVA has been well tolerated up to 22 wks; no serious adverse events.
Mavacamten relieves LVOT obstruction in patients with oHCM beyond standard HCM therapy, while maintaining normal LVEF and improving symptoms. MAVA exposure past 12 weeks is feasible.
Poster Hall, Hall F
Sunday, March 17, 2019, 3:45 p.m.-4:30 p.m.
Session Title: Heart Failure and Cardiomyopathies: Therapy 4
Abstract Category: 14. Heart Failure and Cardiomyopathies: Therapy
Presentation Number: 1285-518
- 2019 American College of Cardiology Foundation