Phase 3, double-blind, randomized, placebo-controlled, multicentre, single country, parallel group trial (112 adult patients) evaluated the efficacy and safety profile of CAMZYOS in septal reduction therapy (SRT)-eligible patients with oHCM1
Trial Design
Select inclusion criteria1-3
- ≥18 years old
- Despite maximally tolerated drug therapy, experienced severe dyspnea or chest pain; symptomatic NYHA Class III/IV* oHCM or Class II with exertional syncope/near syncope†
- LVEF ≥60%
- Peak LVOT gradient ≥50 mmHg at rest or with provocation
- Referred or under active consideration for SRT within 12 months of screening
Select exclusion criteria2,3
- Known infiltrative or storage disorder causing cardiac hypertrophy that mimics oHCM
- Any medical condition that precludes upright exercise stress testing
- Afib present at screening
Trial Participants1
- N=112; CAMZYOS n=56, placebo n=56
- Symptomatic NYHA Class II, III and IV* oHCM
- LVEF ≥60%
- LVOT peak gradient ≥50 mmHg at rest or with provocation
* CAMZYOS is only indicated for NYHA Class II-III adult patients.
Afib=atrial fibrillation; LVEF=left ventricular ejection fraction; KCCQ-23 CSS=Kansas City Cardiomyopathy Questionnaire-23 Clinical Summary Score; LVEF=left ventricular ejection fraction; LVOT=left ventricular outflow tract; NT-proBNP=Nterminal-proBtype natriuretic peptide; NYHA=New York Heart Association; oHCM=obstructive hypertrophic cardiomyopathy; SRT=septal reduction therapy
† Maximally tolerated drug therapy included beta blockers, calcium channel blockers and disopyramide as monotherapy or in combination.
Select patient demographics and disease characteristics1,2
Adapted from the Product Monograph.
Therapy1,2
- Randomized 1:1 to a starting dose of 5 mg of CAMZYOS or placebo once daily for 16 weeks
- Randomization was stratified by type of SRT recommended (surgical myectomy or alcohol ablation) and NYHA functional class
- CAMZYOS dose could be periodically adjusted to maintain a LVEF ≥50% and if warranted by a decrease in LVOT gradient with Valsalva manoeuvre†
- Allowed to continue standard HCM therapy (beta blocker or calcium channel blocker monotherapy)
HCM=hypertrophic cardiomyopathy; LAVI=left atrial volume index; LV=left ventricular; LVEF=left ventricular ejection fraction; LVOT=left ventricular outflow tract; NYHA=New York Heart Association; SD=standard deviation; SRT=septal reduction therapy
* CAMZYOS is only indicated for NYHA Class II-III adult patients.
†Treatment should be interrupted if LVEF <50%, heart failure symptoms or worsening clinical status occurs.
Trial Endpoints
Primary composite endpoint1
Composite endpoint of:
Secondary endpoints:1
Change from baseline to Week 16 in:
- Post-exercise LVOT peak gradient
- NYHA functional class
- NT-proBNP
- Cardiac troponin I
Patient-reported:
- Kansas City Cardiomyopathy Questionnaire-23 Clinical Summary Score (KCCQ-23 CSS)
LVOT=left ventricular outflow tract; NT-proBNP=Nterminal pro-Btype natriuretic peptide; NYHA=New York Heart Association; SRT=septal reduction therapy
* LVOT gradient of ≥50 mmHg and NYHA Class III-IV†, or Class II with exertional syncope or near syncope.
PRIMARY COMPOSITE ENDPOINT
With CAMZYOS: Statistically significant reduction vs. placebo in proportion of patients who met the primary composite endpoint: Proceeded with (prior to or at Week 16) or remained guideline-eligible for SRT (at Week 16)1
Adapted from the Product Monograph.
* Patient decision to proceed with SRT: CAMZYOS treatment group n=2 (4%), placebo group n=2 (4%). SRT status not evaluable (imputed as meeting guideline criteria): CAMZYOS treatment group n=0, placebo group n=2 (4%).1
SRT=septal reduction therapy
Adapted from the Product Monograph.
The guideline-based threshold LVOT gradient for surgery consideration is ≥50 mmHg.4
LVOT=left ventricular outflow tract; SD=standard deviation
* Hierarchical testing of secondary efficacy endpoints showed statistically significant improvement with CAMZYOS vs. placebo.
NYHA Class: Statistically significantly more patients showed improvement in symptom control (≥1 NYHA Class) with CAMZYOS vs. placebo1
Adapted from the Product Monograph.
NYHA=New York Heart Association
* Hierarchical testing of secondary efficacy endpoints showed statistically significant improvement with CAMZYOS vs. placebo.
Treatment difference with CAMZYOS
Geometric mean ratio to baseline difference, 0.33 (95% CI: 0.27-0.42)
p<0.0001*
CAMZYOS -399 ng/L reduction from baseline
vs. placebo 40 ng/L2
Treatment difference with CAMZYOS
Geometric mean ratio to baseline difference, 0.53 (95% CI: 0.40-0.70)
p<0.0001
CAMZYOS -9.2 ng/L reduction from baseline
vs. placebo 0.07 ng/L2
NT-proBNP=N-terminal pro-B-type natriuretic peptide
Geometric mean ratios <1.0 represent an x-fold decrease for CAMZYOS vs. placebo.2
* Hierarchical testing of secondary efficacy endpoints showed statistically significant improvement with CAMZYOS vs. placebo.
SECONDARY ENDPOINTS: PATIENT-REPORTED
KCCQ-23 CSS*: Statistically significantly greater improvement shown in patient-reported scores1
Adapted from the Product Monograph.
Adapted from the Product Monograph.
CSS=Clinical Summary Score; KCCQ-23 CSS=Kansas City Cardiomyopathy Questionnaire 23 Clinical Summary Score; oHCM=obstructive hypertrophic cardiomyopathy
* The KCCQ-23 CSS is a validated patient-reported outcome in oHCM and is composed of the physical limitations (PL) and the total symptom score (TSS) of the KCCQ-23. KCCQ-23 TSS and KCCQ-23 PL were exploratory endpoints.1
† Hierarchical testing of secondary efficacy endpoints showed statistically significant improvement with CAMZYOS vs. placebo.
References: 1. CAMZYOS (mavacamten capsules) Product Monograph. Bristol Myers Squibb Canada, February 14, 2024. 2. Desai MY, et al. Myosin inhibition in patients with obstructive hypertrophic cardiomyopathy referred for septal reduction therapy. J Am Coll Cardiol 2022;80(2):95-108. 3. Desai MY, et al. Supplementary appendix. J Am Coll Cardiol 2022;80(2):95-108. 4. Ommen SR, et al. 2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients with Hypertrophic Cardiomyopathy. Circulation 2020;142(25):e588-631.