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EXPLORER-HCM: Study Design

EXPLORER-HCM: A Groundbreaking Phase 3 Trial for
Symptomatic NYHA Class II–III Obstructive HCM1,2

A randomized, double blind, placebo-controlled trial evaluated the efficacy and safety of CAMZYOS vs placebo1,2

screening phase1,2

Select inclusion criteria1,2
  • ≥18 years old, body weight >45 kg at screening
  • NYHA class II or III
  • Diagnosis of obstructive HCM
  • Left ventricular ejection fraction (LVEF) ≥55%
  • LVOT ≥50 mmHg at rest or with provocation
  • Able to safely perform upright cardiopulmonary
    exercise testing (CPET)
Select exclusion criteria1,2
  • Known infiltrative or storage disorder that mimics
    obstructive HCM (Fabry disease, amyloidosis, or
    Noonan syndrome with left ventricular hypertrophy)
  • Underwent SRT within 6 months prior to screening or
    plans to have SRT during the study
  • Treatment (within 14 days prior to screening) or planned
    treatment with disopyramide, ranolazine, or a
    combination of beta blockers (BBs) and calcium channel
    blockers (CCBs); prior treatment with cardiotoxic agents
Randomized 1:1 (N=251)2

treatment phase1,2

CAMZYOS and placebo were administered orally, once a day. Dosage was monitored and adjusted (as needed) at weeks 8 and 14 to optimize patient response (decrease in LVOT gradient with Valsalva maneuver), maintain LVEF ≥50%, and was further informed by plasma concentrations of CAMZYOS

8-week washout phase1,2

Study drug was discontinued and participants returned for key assessments at week 38

92% of patients were on background
therapy with BBs or CCBs2*
CAMZYOS (n=119/123) | Placebo (n=112/128)
  • *Patients on BBs or CCBs were allowed to continue
    background therapy.2

See select baseline patient
characteristics below

The primary composite functional endpoint and hierarchical secondary endpoints
were designed to assess treatment parameters for symptomatic NYHA class II–III
obstructive HCM2

Primary composite functional endpoint measured change from baseline to week 30 in symptoms (NYHA) and functional
capacity (pVO2)1,2

≥1 NYHA class improvement AND ≥1.5 mL/kg/min improvement in pVO2
No worsening in NYHA class AND ≥3.0 mL/kg/min improvement in pVO2
Hierarchical secondary endpoints1,2†:(Measured from baseline to week 30)
  • Change in post-exercise LVOT gradient
  • Change in pVO2
  • Proportion of patients with ≥1 NYHA
    class improvement
  • Change in KCCQ-23–CSS
  • Change in HCMSQ-SoB
Select prespecified exploratory endpoints1,2:(Not powered for statistical significance)
  • Post-exercise LVOT peak gradient <50 mmHg
  • Post-exercise LVOT peak gradient <30 mmHg
  • Proportion of patients with reductions in serum concentrations
    of N-terminal pro B-type natriuretic peptide (NT-proBNP) and
    high-sensitivity cardiac troponin I (hs-cTnI)
  • All assessments for secondary endpoints were
    performed and Type I error was controlled in
    hierarchical order (sequence as indicated above)
    upon achieving significance in the primary endpoint
    (with two-tailed P<0.05 required to proceed).2

HCM=hypertrophic cardiomyopathy; HCMSQ-SoB=Hypertrophic Cardiomyopathy Symptom Questionnaire Shortness of Breath subscore; KCCQ-23–CSS=Kansas City Cardiomyopathy Questionnaire (23-item version)–Clinical Summary Score; LVOT=left ventricular outflow tract; NYHA=New York Heart Association; pVO2=peak oxygen consumption; SRT=septal reduction therapy.

Select baseline patient characteristics in EXPLORER-HCM1,2

Select baseline patient characteristics

Values in the table are mean ± SD, n (%) CAMZYOS (n=123) Placebo (n=128)
Age, mean (SD), years 59 (12.2) 59 (11.8)
Women, n (%) 57 (46) 45 (35)
Race, n (%)
Black or African American
American Indian or Alaska Native
115 (94)
1 (1)


4 (3)
3 (2)
114 (89)
5 (4)

1 (1)

2 (2)
6 (5)
Background HCM
treatment, n (%)
Beta blocker
Calcium channel blocker‡
94 (76)
25 (20)
95 (74)
17 (13)
NYHA class, n (%)
Class II
Class III
88 (72)
35 (28)
95 (74)
33 (26)
pVO2 mean (SD), mL/kg/min
18.9 (4.9)

19.9 (4.9)
LVOT gradient at
baseline, mean
(SD), mmHg
72 (32)
86 (34)
74 (32)
84 (36)
LVEF, mean (SD), (%) 74 (6) 74 (6)
Critical cardiac history
Atrial fibrillation, n (%)
defibrillator, n (%)
Prior invasive SRT, n (%)
12 (10)
27 (22)

11 (9)
23 (18)
29 (23)

8 (6)
  • Nondihydropyridine calcium channel blockers.2
  • §Data missing for one patient in the CAMZYOS group and one patient in the placebo group.2

SD=standard deviation.

Study procedures used in EXPLORER-HCM to determine
the efficacy and safety of CAMZYOS

Open for study procedures >

EXPLORER-LTE: Study Design

EXPLORER-LTE: A Cohort of MAVA-LTE, a 5-Year Extension Designed to Evaluate Long-Term Safety, Efficacy, and Clinically Guided Dosing for CAMZYOS3,4

To be eligible to enroll in the EXPLORER-LTE cohort of MAVA-LTE, patients had to complete EXPLORER-HCM, including the 8-week washout period. Of the 251 patients|| who completed EXPLORER-HCM, 231 enrolled in MAVA-LTE in the EXPLORER-LTE cohort, which is being evaluated in a single-arm trial without an active comparator.

Primary Endpoint CAMZYOS® (mavacamten) vs Placebo, Chart
EXPLORER-LTE 5-Year Treatment Phase EXPLORER-LTE 5-Year Treatment Phase
  • ||Patients enrolled in EXPLORER-LTE were part of either the CAMZYOS or placebo arm in the EXPLORER-HCM trial.3-5
  • This is not consistent with the current approved dosing schedule per the U.S. Full Prescribing Information.1

MAVA-LTE: EXPLORER-LTE cohort study limitations and additional information:

  • These data are not included in the CAMZYOS U.S. Full Prescribing Information. Caution should be used in interpreting the data as data were not statistically tested for significance but are only descriptive in nature4
  • MAVA-LTE, including the EXPLORER-LTE cohort, is a single-arm study without active comparator; patients in EXPLORER-LTE were part of either the CAMZYOS or placebo group in EXPLORER-HCM; therefore, baseline characteristics for EXPLORER-LTE changed due to time and consolidation of both arms to one cohort5
  • There are limitations with the data, including decreased sample size and different continuation rates based on the continued involvement of responders and attrition of nonresponders5
  • The EXPLORER-LTE cohort of MAVA-LTE included 14 patients who were NYHA class I at screening. These patients were included in the EXPLORER-HCM trial; 5 had received CAMZYOS, and 9 were in the placebo group3

Select Patient Baseline# Characteristics for EXPLORER-LTE3

  • #Baseline is defined as last non-missing measurement before the first dose of CAMZYOS in MAVA-LTE.3
  • **14 patients improved from NYHA class II–III to NYHA class I between EXPLORER-HCM baseline and MAVA-LTE baseline.3

IQR=interquartile range.

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  1. CAMZYOS [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2023.
  2. Olivotto I, Oreziak A, Barriales-Villa R, et al; EXPLORER-HCM study investigators. Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2020;396(10253):759-769. doi:10.1016/S0140-6736(20)31792-X
  3. Garcia-Pavia P, Oreziak A, Masri A, et al. Long-term effects of mavacamten treatment in obstructive hypertrophic cardiomyopathy (HCM): updated cumulative analysis of the EXPLORER cohort of MAVA-long-term extension (LTE) study up to 120 weeks. Presented at ESC 2023. Oral presentation 835382.
  4. Data on file. BMS-REF-MAVA-0039. Princeton, NJ: Bristol-Myers Squibb Company; 2023.
  5. Rader F, Oręziak A, Choudhury L, et al. Mavacamten treatment for symptomatic obstructive hypertrophic cardiomyopathy: interim results from the MAVA-LTE study, EXPLORER-LTE Cohort. J Am Coll Cardiol. 2024;12(1):164-177.