EXPLORER-HCM Clinical Trial

EXPLORER-HCM was a Phase 3, double-blind, randomised, placebo-controlled, parallel-arm, multicentre, international trial that evaluated the efficacy and safety profile of CAMZYOS (n=123) vs placebo (n=128) in adult patients with symptomatic NYHA class II-III obstructive HCM, LVEF ≥55%, and LVOT peak gradient ≥50 mmHg at rest or with provocation at time of obstructive HCM diagnosis and Valsalva LVOT gradient ≥30 mmHg at screening.^1,2

EXPLORER-HCM study design^1–3

*Consisting of beta blockers and calcium channel blockers.²
^†Dose adjustments occurred per a blinded titration scheme at Weeks 8 and 14. Individualised doses of 2.5, 5, 10, or 15 mg were ultimately administered to achieve target reduction in LVOT gradient of <30 mmHg while maintaining LVEF ≥50% and CAMZYOS concentration between 350 ng/mL and 700 ng/mL.²

Proportion of patients who received background therapy with a beta blocker or calcium channel blocker in EXPLORER-HCM^1,2

EXPLORER-HCM: inclusion and exclusion criteria^1,2

The inclusion and exclusion criteria in EXPLORER-HCM were developed to prioritise patient safety and to include a representative patient population of real-world symptomatic obstructive HCM.²

Inclusion criteria^1,2

≥18 years old
Obstructive HCM (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
Able to safely perform upright cardiopulmonary exercise testing

Exclusion criteria^1,2

History of syncope or sustained ventricular tachyarrhythmia with exercise within 6 months prior to screening
QT interval corrected using Fridericia’s formula more than 500 ms
Dual therapy with BBs and CCBs or monotherapy with disopyramide
- Patients were allowed to continue standard therapy for HCM, such as monotherapy of BBs or CCBs
Underwent SRT within 6 months prior to screening
Atrial fibrillation on screening ECG
Persistent or permanent atrial fibrillation not on anticoagulation for 4 weeks or more or not adequately rate-controlled within 6 months prior to screening
Known infiltrative or storage disorder causing cardiac hypertrophy that mimicked obstructive HCM (such as Fabry disease, amyloidosis, or Noonan syndrome with LV hypertrophy)

EXPLORER-HCM: baseline demographics and disease characteristics²

Baseline demographics and disease characteristics were balanced between the CAMZYOS and placebo arms.²

EXPLORER-HCM baseline characteristics²

Adapted from Olivotto I et al. 2020.²
*96% of patients in the CAMZYOS treatment arm received background therapy with beta blocker or calcium channel blocker (76% [94/123] and 20% [25/123], respectively) vs 87% in the placebo arm (74% [95/128] and 13% [17/128], respectively).^1,2
^†Data missing for one patient in the CAMZYOS arm.²

EXPLORER-HCM endpoints^1,2

Endpoints assessed included a mixture of objective clinical measures (such as LVOT peak gradient and pVO₂) and subjective
patient-reported outcomes (such as KCCQ-23 CSS and HCMSQ-SoB domain score).^1,2 The primary endpoint was a composite designed to assess the change at Week 30 in exercise capacity (measured by pVO₂) and patient symptoms (measured by NYHA class), defined as a ≥1.5 mL/kg/min increase in pVO₂ and ≥1 NYHA class improvement or a ≥3.0 mL/kg/min increase in pVO₂ and no worsening in NYHA class.^1,2

Primary endpoint^1,2

Secondary and exploratory endpoints^1,2

*Assessing change from baseline to Week 30.^1,2

Explore the clinical efficacy

BB, beta blocker; CCB, calcium channel blocker; ECG, electrocardiogram; HCM, hypertrophic cardiomyopathy; HCMSQ-SoB, Hypertrophic Cardiomyopathy Symptom Questionnaire Shortness of Breath; hs-cTnI, high-sensitivity cardiac troponin I; KCCQ-23 CSS, Kansas City Cardiomyopathy Questionnaire-23 Clinical Summary Score; LV, left ventricular; LVEF, left ventricular ejection fraction; LVOT, left ventricular outflow tract; NT-proBNP, N-terminal pro-B-type natriuretic peptide; NYHA, New York Heart Association; pVO₂, peak oxygen consumption; SAE, serious adverse event; SD, standard deviation; SoC, standard of care; SRT, septal reduction therapy; TEAE, treatment-emergent adverse event.

References

CAMZYOS (mavacamten) Summary of Product Characteristics.
Olivotto I et al. Lancet. 2020;396(10253):759–769.
Ho CY et al. Circ Heart Fail. 2020;13(6):e006853.

EXPLORER-HCM study design1–3

Proportion of patients who received background therapy with a beta blocker or calcium channel blocker in EXPLORER-HCM1,2

EXPLORER-HCM: inclusion and exclusion criteria1,2

EXPLORER-HCM: baseline demographics and disease characteristics2

EXPLORER-HCM endpoints1,2