Efficacy and safety of extended treatment with aficamten in patients with symptomatic obstructive hypertrophic cardiomyopathy: Results from FOREST-HCM
Albree Tower-Rader, Ahmad Masri, Michael E. Nassif, Theodore P. Abraham, Roberto Barriales-Villa, Lubna Choudhury, Robert M. Cooper, Perry M. Elliott, Martin S. Maron, Iacopo Olivotto, Artur Oreziak,
Anjali T. Owens, Scott D. Solomon, Chiara Melloni, Sara Saberi1, on behalf of the FOREST-HCM Investigators
1University of Michigan, Ann Arbor, Michigan, USA
AUGUST 31, 2025
Background
Aficamten in obstructive hypertrophic cardiomyopathy (oHCM)
-
Safe and effective in lowering left ventricular outflow tract gradients (LVOT-G), up to 1 year
-
Improved symptom burden and exercise capacity1-3
1. Maron MS, et al J Am Coll Cardiol 2023;81(1):34-45. 2. Maron MS, et al. Eur Heart J 2025 May 17:ehaf364. 3. Saberi S, et al. JACC Heart Fail 2025;13(8):102496.
Purpose and Study Design
Purpose - To evaluate the long-term efficacy and tolerability of aficamten in oHCM
Population - Eligible patients completing a parent study (REDWOOD-HCM; SEQUOIA-HCM; MAPLE-HCM) were offered participation in FOREST-HCM
Titration and Monitoring* - Patients underwent echocardiographically guided titration every 2-weeks within the first 6 weeks, with aficamten dose increased in 5 mg increments to a maximum of 20 mg daily. Monitoring visits occurred every 12 weeks thereafter
Dosing decisions - Dose adjustments were made by the treating physician integrating both their clinical impression and echocardiographic measures (LVEF and LVOT-G) - mimicking real-world clinical practice
*Protocol amendment 6 allows for more flexible titration visit intervals and monitoring every 6 months in selected patients
LVEF, left ventricular ejection fraction; LVOT-G, left ventricular outflow tract gradient; oHCM, obstructive hypertrophic cardiomyopathy
Results
Baseline Characteristics
|
Characteristica |
All Patientsb N=296 |
|
Age (years), mean ± SD |
61.0 ± 12.3 |
|
Female, n (%) |
131 (44.3) |
|
White, n (%) |
278 (93.9) |
|
BMI (kg/m2), mean ± SD |
28.9 ± 4.2 |
|
Known history of HCM-causing gene variant or family history of HCM, n (%) |
101 (34.1) |
|
Background HCM therapy, n (%) |
|
|
Beta-blocker monotherapy |
147 (49.7) |
|
Non-dihydropyridine CCB monotherapy |
51 (17.2) |
|
Disopyramide |
44 (14.9) |
|
Beta-blocker + CCB |
6 (2.0) |
|
No background HCM medications, n (%) |
48 (16.2) |
|
Characteristica |
All Patientsb N=296 |
|
Mean Duration of exposure, years (range) |
1.2 (0.005-3.26) |
|
Total person-years of exposure |
352.2 |
|
NYHA functional class, n (%) |
|
|
I |
10 (3.4) |
|
II |
168 (56.8) |
|
III |
118 (39.9) |
|
KCCQ-CSS mean ± SD |
70.5 ± 19.4 |
|
LVEF (%), mean ± SD |
68.4 ± 5.8 |
|
Resting LVOT-G (mm Hg), mean ± SD |
56.4 ± 37.3 |
|
Valsalva LVOT-G (mm Hg), mean ± SD |
93.8 ± 42.5 |
|
NT-proBNP (pg/mL), median [QI, Q3] |
776.5 [348.5, 1531.5] |
|
hs-cardiac-Tnl (ng/L), median [QI, Q3] |
11.2 [5.8, 19.8] |
an (%) unless otherwise stated.
bNumber of participants from each parent study: REDWOOD-HCM, n=45; SEQUOIA-HCM, n=222; MAPLE-HCM, n=29.
BMI, body mass index; CCB, non-dihydropyridine calcium channel blocker; HCM, hypertrophic cardiomyopathy; hs-cardiac-TnI, high-sensitivity cardiac troponin I; KCCQ-CSS, Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score; LVEF, left ventricular ejection fraction; LVOT-G, left ventricular outflow tract gradient; NT-proBNP, N-terminal pro-B-type natriuretic peptide; NYHA, New York Heart Association; Q, quartile
Results
Effect of Aficamten on Clinical HCM Characteristics
-
Resting LVOT Gradient
30 mmHg
100
Resting LVOT-G (mmHg), mean ±SD
90
80
70
60
50
40
30
20
10
0
-
Valsalva LVOT Gradient
50 mmHg
30 mmHg
Valsalva LVOT-G (mmHg), mean ±SD
100
50
30
0
0246
12 24 36 48 60 72 84 96 108 120 132 144 156 168
Weeks
0246
12 24 36 48 60 72 84 96 108 120 132 144 156 168
Weeks
n = 291
282
263
242 172 106 64 47 44 42 39 36 25 9 3
n = 292
283
263
243 172 106 64 47 44 42 39 36 25 9 3
-
Left Ventricular Ejection Fraction
50%
LVEF (%), mean ±SD
80
70
D
150 pg/mL
NT-proBNP (pg/mL)
1000
750
NT-proBNP
60
50
0246
12 24 36 48 60 72 84 96 108 120 132 144 156 168
Weeks
500
250
150
0
0
12 24 36 48 60 72 84 96 108 120 132 144 156 168
Weeks
n = 292
283
264
244 173 106 64 47 44 42 39 36 25 9 3
n = 292
276
263
243 171 105 63 47 44 42 39 36 25 9 3
Shaded area represents the titration phase.
HCM, hypertrophic cardiomyopathy; LVEF, left ventricular ejection fraction; LVOT-G, left ventricular outflow tract gradient; NT-proBNP, N-terminal pro-B-type natriuretic peptide.
Attachments
Disclaimer
Cytokinetics Incorporated published this content on August 31, 2025, and is solely responsible for the information contained herein. Distributed via Public Technologies (PUBT), unedited and unaltered, on August 31, 2025 at 18:06 UTC.
