Phase 3, double-blind, randomized, placebo-controlled, multicentre, international, parallel-group trial evaluated the efficacy and safety profile of CAMZYOS for patients with NYHA Class II-III oHCM1
Trial Design
Select inclusion criteria2
- ≥18 years old
- oHCM (unexplained left ventricular hypertrophy with maximal left ventricular wall thickness of ≥15 mm [or ≥13 mm if familial HCM])
- Symptomatic NYHA Class II or III
- LVEF ≥55%
- Peak LVOT gradient ≥50 mmHg at rest or with provocation
Select exclusion criteria2
- Dual therapy with beta blocker and calcium channel blocker or monotherapy with disopyramide or ranolazine
- Syncope or sustained ventricular tachyarrhythmia with exercise ≤6 months before screening
- Atrial fibrillation on screening ECG
- Septal reduction therapy ≤6 months before screening or planned during study
- Known infiltrative or storage disorders causing cardiac hypertrophy that may mimic oHCM
ECG=electrocardiogram; HCM=hypertrophic cardiomyopathy; HCMSQ SoB=Hypertrophic Cardiomyopathy Symptom Questionnaire Shortness-of-Breath subscore; KCCQ-23 CSS=Kansas City Cardiomyopathy Questionnaire-23 Clinical Summary Score; LVEF=left ventricular ejection fraction; LVOT=left ventricular outflow tract; NYHA=New York Heart Association; oHCM=obstructive hypertrophic cardiomyopathy; pVO2=peak oxygen consumption
Trial Participants1
- N=251; CAMZYOS n=123, placebo n=128
- Symptomatic NYHA Class II and III oHCM
- LVEF ≥55%
- LVOT peak gradient ≥50 mmHg at rest or with provocation
Select patient characteristics1
Adapted from the Product Monograph.
Background therapy1
Majority of patients received conventional background HCM treatment:
- 96% of CAMZYOS patients (beta blockers 76%, calcium channel blockers 20%)
- 87% of placebo patients (beta blockers 74%, calcium channel blockers 13%)
- Exclusion: disopyramide or ranolazine
HCM=hypertrophic cardiomyopathy; LVEF=left ventricular ejection fraction; LVOT=left ventricular outflow tract; NYHA=New York Heart Association; oHCM=obstructive hypertrophic cardiomyopathy
Trial Endpoints
Primary composite endpoint: Exercise capacity and symptoms1
Composite of change at Week 30 from baseline in exercise capacity (measured by pVO2) and symptoms (measured by NYHA Class)
Patients with change from baseline in pVO2 ≥1.5 mL/kg/min
AND
Improvement in NYHA Class ≥1 at Week 30
Patients with change from baseline in pVO2 ≥3.0 mL/kg/min
AND
No worsening in NYHA Class at Week 30
Patients with change from baseline in pVO2 ≥3.0 mL/kg/min
AND
Improvement in NYHA Class ≥1 at Week 30
Secondary endpoints: LVOT peak gradient, functional capacity and health status1
Observed:
- Change from baseline to Week 30 in:
- Post-exercise LVOT peak gradient
- pVO2
- Proportion of patients with improvement of ≥1 NYHA Class at Week 30
Patient-reported:
- Kansas City Cardiomyopathy Questionnaire-23 Clinical Summary Score (KCCQ-23 CSS)
- Hypertrophic Cardiomyopathy Symptom Questionnaire Shortness-of-Breath subscore (HCMSQ SoB)
LVOT=left ventricular outflow tract; NYHA=New York Heart Association; oHCM=obstructive hypertrophic cardiomyopathy; pVO2=peak oxygen consumption
PRIMARY COMPOSITE ENDPOINT
With CAMZYOS: Statistically significant improvement shown in symptoms and exercise capacity vs. placebo in patients with symptomatic oHCM1
CAMZYOS met the primary composite endpoint measured by change in symptoms (NYHA Class) and exercise capacity (pVO2) from baseline to Week 30.1
Adapted from the Product Monograph.
NYHA=New York Heart Association; oHCM=obstructive hypertrophic cardiomyopathy; pVO2=peak oxygen consumption
Patients achieving the primary endpoint at Week 30.1
Adapted from the Product Monograph.
NYHA=New York Heart Association; pVO2=peak oxygen consumption
Adapted from the Product Monograph.
In MAVA-LTE*
- Sustained reductions shown in Valsalva LVOT gradient: -55.3 mmHg change baseline to Week 180.
- 83% of patients (n=191) achieved a reduced Valsalva LVOT gradient of ≤30 mmHg, or below obstructive levels (until data cutoff).
Peak VO2: Greater mean increase in pVO2 shown with CAMZYOS vs. placebo1
Adapted from the Product Monograph.
LVOT=left ventricular outflow tract; pVO2=peak oxygen consumption
* The duration of this study is longer than the data in the Product Monograph.
SECONDARY ENDPOINTS
NYHA Class: Statistically significantly more patients had improvement of ≥1 NYHA Class with CAMZYOS vs. placebo1
Adapted from the Product Monograph.
NYHA Class I achieved at Week 30:
With CAMZYOS, 50% of patients (61/123) achieved
NYHA Class I vs. 21% (27/128) placebo1
NYHA=New York Heart Association
NYHA Class: Status achieved at Week 301
50% of all patients on CAMZYOS reached NYHA
Class I, regardless of class at baseline vs. 21% placebo
(61/123 vs. 27/128)
In MAVA-LTE*
- 77.9% of patients improved by at least one NYHA class from baseline to Week 180.
- At Week 180, 66% were NYHA Class I, 31% were NYHA Class II, 3% were NYHA Class III.
NYHA=New York Heart Association
* The duration of this study is longer than the data in the Product Monograph.
SECONDARY ENDPOINTS: PATIENT-REPORTED
KCCQ-23 CSS*: Statistically significantly greater improvement shown in patient-reported combined physical limitations and total symptom burden scores with CAMZYOS vs. placebo1
Adapted from the Product Monograph.
Adapted from the Product Monograph.
KCCQ-23 CSS=Kansas City Cardiomyopathy Questionnaire-23 Clinical Summary Score; LS=least squares; oHCM=obstructive hypertrophic cardiomyopathy; SE=standard error
* The KCCQ-23 CSS is a validated patient-reported outcome in oHCM and is composed of the physical limitations and the total symptom burden scores of the KCCQ-23. The Clinical Summary Score (CSS) ranges from 0 to 100, with higher scores representing better health status.
HCMSQ SoB*: Statistically significantly greater improvement shown in patient-reported frequency and severity of shortness of breath with CAMZYOS vs. placebo1
Adapted from the Product Monograph.
Adapted from the Product Monograph.
HCMSQ SoB=Hypertrophic Cardiomyopathy Symptom Questionnaire Shortness of Breath subscore; LS=least squares; oHCM=obstructive hypertrophic cardiomyopathy; SE=standard error
* The HCMSQ SoB domain score is a validated patient-reported outcome in oHCM and measures frequency and severity of shortness of breath. The HCMSQ Shortness of Breath (SoB) domain score ranges from 0 to 18, with lower scores representing less shortness of breath.
Long-term results
MAVA-LTE: A cohort of the EXPLORER-HCM trial
5-year extension designed to evaluate long-term efficacy, safety and clinically guided dosing for CAMZYOS (N=224); mean duration 32 weeks
Long-term CAMZYOS treatment resulted in sustained improvements in cardiac function and symptoms in patients with oHCM: >739 patient-years of exposure3
The duration of this study is longer than the data in the Product Monograph.
HCMSQ SoB=Hypertrophic Cardiomyopathy Symptom Questionnaire Shortness-of-Breath subscore; LVEF=left ventricular ejection fraction; LVOT=left ventricular outflow tract; NT-proBNP=Nterminal pro-Btype natriuretic peptide; NYHA=New York Heart Association; oHCM=obstructive hypertrophic cardiomyopathy; SD=standard deviation
References: 1. CAMZYOS (mavacamten capsules) Product Monograph. Bristol Myers Squibb Canada. 2. Olivotto I, et al. Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): a randomized, double-blind, placebo-controlled, phase 3 trial. Lancet 2020;396:759-69. 3. Garcia-Pavia P, et al. Long-term effect of mavacamten in obstructive hypertrophic cardiomyopathy. Eur Heart J 2024;45(47):5071-83.