VALOR-HCM Clinical Trial

VALOR-HCM is a Phase 3, double-blind, randomised, multicentre, placebo-controlled trial evaluating the efficacy and safety profile of CAMZYOS (n=56) vs placebo (n=56) in eligible adult patients with severely symptomatic drug-refractory obstructive HCM, and NYHA class III/IV, or class II with exertional syncope or near syncope and dynamic LVOT obstruction ≥50 mmHg at rest or with provocation (i.e., Valsalva or exercise), and LVEF ≥60%.^1–3

VALOR-HCM study design^1–3

*Background therapies included beta blockers, calcium channel blockers, and disopyramide. Only 5.4% (3/56) of patients on each treatment arm did not receive any background medication due to intolerance.²
^†Dose adjustments occurred per a blinded titration scheme at Weeks 4, 8 and 12. Echocardiography was performed every 4 weeks and used to titrate individualised doses of 2.5, 5, 10, or 15 mg based on LVOT gradient and LVEF.^2,3

VALOR-HCM: inclusion and exclusion criteria^2,3

Inclusion criteria²

≥18 years old
Severe dyspnoea or chest pain despite maximally tolerated medical therapy
NYHA class III/IV or class II with exertional syncope or near syncope
Severe LVOT gradient ≥50 mmHg at rest or with provocation
Documented LVEF ≥60%
Obstructive HCM (maximum septal wall thickness by a core laboratory ≥15 mm or ≥13 mm if familial HCM)
Referral for SRT within past 12 months and actively considering scheduling the procedure

Exclusion criteria³

Known infiltrative or storage disorder causing cardiac hypertrophy that mimics obstructive HCM (such as Fabry disease, amyloidosis, or Noonan syndrome)
Moderate-to-severe aortic stenosis
Planned invasive procedure during first 32 weeks of study
Papillary muscle or mitral valve in need of repair or any other intracardiac procedure planned
Medical conditions precluding upright exercise stress testing
Previously treated with invasive SRT (surgical myectomy or percutaneous ASA)*
Atrial fibrillation on screening ECG
Planned defibrillator placement or pulse generator change during the first 32 weeks of study
Acute or serious comorbid condition

*However, if the participant has a history of a suboptimal prescreening ECG of an ASA, the participant may be included after consultation with the Bristol Myers Squibb or CRO medical monitor.³

VALOR-HCM: patient demographics²

Patient demographics were balanced between the CAMZYOS and placebo arms, being representative of real-world patients with severely symptomatic obstructive HCM who were eligible for SRT (ASA or myectomy).²

Adapted from Desai MY et al. 2022.²
*Background therapies included beta blockers, calcium channel blockers, and disopyramide. Only 5.4% (3/56) of patients on each treatment arm did not receive any background medication due to intolerance.²

VALOR-HCM endpoints^1–3

The primary endpoint was designed to evaluate the value of CAMZYOS in reducing the proportion of patients who would meet guideline criteria for SRT or chose to undergo SRT vs placebo at Week 16. The primary endpoint was a composite of patient decision to proceed with SRT prior to or at Week 16 or patients who remain SRT eligible (defined as a LVOT gradient of ≥50 mmHg and NYHA class III-IV, or class II with exertional syncope or near syncope) at Week 16.¹

Primary endpoint¹

Secondary and safety endpoints^1–3

Explore eligibility for surgery

ACC/AHA, American College of Cardiology/American Heart Association; ASA, alcohol septal ablation; BB, beta blocker; CCB, calcium channel blocker; CV, cardiovascular; ECG, electrocardiogram; ESC, European Society of Cardiology; HCM, hypertrophic cardiomyopathy; HF, heart failure; ICD, implantable cardioverter-defibrillator; KCCQ-23 CSS, Kansas City Cardiomyopathy Questionnaire-23 Clinical Summary Score; LVEF, left ventricular ejection fraction; LVOT, left ventricular outflow tract; NT-proBNP, N-terminal pro-B-type natriuretic peptide; NYHA, New York Heart Association; SD, standard deviation;  SoC, standard of care; SRT, septal reduction therapy.

References

CAMZYOS (mavacamten) Summary of Product Characteristics.
Desai MY et al. J Am Coll Cardiol. 2022;80(2):95–108.
Desai MY et al. Am Heart J. 2021;239:80–89.

VALOR-HCM study design1–3

VALOR-HCM: inclusion and exclusion criteria2,3

VALOR-HCM: patient demographics2