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 placebo1-3

5-week
screening phase3

Select inclusion criteria4
  • ≥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 criteria2,4
  • 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
CAMZYOS(n=123)
Randomized 1:1 (N=251)2
Placebo(n=128)

30-week
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
OR
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
    ≤30 mmHg
  • Change in pVO2
  • Proportion of patients with ≥1 NYHA
    class improvement
  • Change in KCCQ-23–CSS
  • Change in HCMSQ-SoB
Select prespecified exploratory endpoints2,5:(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

HCMSQ-SoB=Hypertrophic Cardiomyopathy Symptom Questionnaire Shortness of Breath subscore; KCCQ-23-CSS–Kansas City Cardiomyopathy Questionnaire
(23-item version) Clinical Summary Score; LVEF=left ventricle ejection fraction; LVOT=left ventricular outflow tract; NYHA=New York Heart Association; SRT=septal reduction therapy.

Select baseline patient characteristics in EXPLORER-HCM1,2

Select patient baseline characteristics

  CAMZYOS (n=123) Placebo (n=128)
Age, mean (SD), years 59 (12.2) 59 (11.8)
Women, n (%) 57 (46) 45 (35)
Race, n (%)
White
Black or African American
American Indian or Alaska Native
Asian
Unknown
115 (94)
1 (1)

0

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
Valsalva
Post-excercise§
72 (32)
86 (34)
74 (32)
84 (36)
LVEF, mean (SD), (%) 74 (6) 74 (6)
Critical cardiac history
Atrial fibrillation, n (%)
Implantable
cardioverter-
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 >

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References:

  1. CAMZYOS [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2022.
  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.
  3. Ho CY, Olivotto I, Jacoby D, et al. Study design and rationale of EXPLORER-HCM: evaluation of mavacamten in adults with symptomatic obstructive hypertrophic cardiomyopathy. Circ Heart Fail. 2020;13(6):e006853.
  4. Ho CY, Olivotto I, Jacoby D, et al. Study design and rationale of EXPLORER-HCM: evaluation of mavacamten in adults with symptomatic obstructive hypertrophic cardiomyopathy. Circ Heart Fail. 2020;13(6):e006853 [supplementary appendix].
  5. Olivotto I. Efficacy and safety of mavacamten in adults with symptomatic obstructive hypertrophic cardiomyopathy: results of the EXPLORER-HCM study. Presented at ESC Congress The Digital Experience; 2020.