If approved, CAMZYOS would be the first cardiac myosin inhibitor in Europe that specifically targets the source of obstructive HCM

Recommendation based on positive Phase 3 EXPLORER-HCM and VALOR-HCM trials demonstrating benefit in patients receiving CAMZYOS versus placebo

PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE: BMY) today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended approval of CAMZYOS® (mavacamten) for the treatment of symptomatic (New York Heart Association, NYHA, class II-III) obstructive hypertrophic cardiomyopathy (HCM) in adult patients. The European Commission (EC), which has the authority to approve medicines for the European Union (EU), will now review the CHMP opinion.

“Obstructive hypertrophic cardiomyopathy can be a debilitating and life-changing heart disease, reducing physical functioning and overall well-being, and often runs in families. For patients in the EU, there is yet to be an approved therapy that targets the underlying cause of this disease, despite its global prevalence and debilitating symptoms,” said Roland Chen, M.D., Senior Vice President, Cardiovascular Development at Bristol Myers Squibb. “We are encouraged by the CHMP’s positive recommendation, which puts us one step closer to offering patients in the EU a first-in-class treatment for obstructive HCM, and reinforces our commitment to delivering transformative cardiovascular therapies to patients worldwide.”

The positive opinion is based upon efficacy and safety results from two Phase 3 trials, EXPLORER-HCM and VALOR-HCM. Results from the Phase 3 EXPLORER-HCM trial, which evaluated CAMZYOS in patients with symptomatic obstructive HCM versus placebo, met all primary and secondary endpoints with statistical significance. EXPLORER-HCM showed CAMZYOS demonstrated a clear treatment effect, with clinically meaningful improvements in exercise capacity and symptoms, and functional status, as well as clinically meaningful improvement in left ventricular outflow tract obstruction. Results from the Phase 3 VALOR-HCM study evaluated CAMZYOS in patients with symptomatic obstructive HCM who met the 2011 ACC/AHA or 2014 ESC guideline criteria for septal reduction therapy (SRT) and who were referred for an invasive procedure. VALOR-HCM met statistical significance across all primary and secondary endpoints showing a valuable improvement across key cardiac measures which resulted in a clinically meaningful reduction in need or eligibility for SRT among CAMZYOS-treated patients versus placebo.

On April 28, 2022, the U.S. Food and Drug Administration (FDA) approved CAMZYOS for the treatment of adults with symptomatic NYHA class II-III obstructive HCM to improve functional capacity and symptoms. Please see important safety information, including Boxed WARNING, from the U.S. prescribing information below.

Bristol Myers Squibb thanks the patients and investigators involved in both clinical trials.

About EXPLORER-HCM

The EXPLORER-HCM Phase 3 trial (NCT03470545) was a double-blind, randomized, placebo-controlled, parallel group trial that enrolled a total of 251 adult patients with symptomatic (NYHA class II or III), obstructive hypertrophic cardiomyopathy. All participants had measurable left ventricular ejection fraction (LVEF) ≥55% and at least one peak LVOT gradient ≥50 mmHg (at rest or with provocation at diagnosis); in addition, Valsalva LVOT gradient ≥30 mmHg at baseline was required at screening. Ninety-two percent of patients were on background therapies of a beta blocker or calcium channel blocker. The primary endpoint was a composite functional endpoint, assessed at 30 weeks, and was defined as the proportion of patients who achieved either improvement of mixed venous oxygen tension (pVO2) by ≥1.5 mL/kg/min plus improvement in NYHA class by at least 1 or improvement of pVO2 by ≥3.0 mL/kg/min plus no worsening in NYHA class. Key secondary endpoints include impact on exercise gradient LVOT, pVO2, NYHA Class and Kansas City Cardiomyopathy Questionnaire (KCCQ) and Hypertrophic Cardiomyopathy Symptom Questionnaire (HCMSQ) at Week 30.

About VALOR-HCM

VALOR-HCM (NCT04349072) is a randomized, double-blind, placebo-controlled, multicenter Phase 3 study of patients with symptomatic, obstructive HCM (NYHA class III-IV) who meet guideline criteria for septal reduction therapy (SRT) and have been referred for an invasive procedure. The study enrolled 112 patients in the U.S., randomized on a 1:1 basis to receive mavacamten or placebo. Ninety-five percent of patients were on background therapies of a beta blocker, calcium channel blocker, disopyramide or a combination. The primary endpoint is a composite of the number of patients who decide to proceed with SRT prior to or at Week 16 and the number of patients who remain SRT-guideline eligible (LVOT gradient of ≥50 mmHg and NYHA Class III-IV or Class II with exertional symptoms of syncope or near syncope) at Week 16. Key secondary endpoints include impact on exercise gradient LVOT, NYHA Class and Kansas City Cardiomyopathy Questionnaire (KCCQ) and biomarkers at Week 16. The results of the VALOR-HCM study were submitted to the FDA for an expanded indication to reduce the need for septal reduction therapy (SRT). The FDA accepted the supplemental new drug application (sNDA) and assigned a Prescription Drug User Fee Act (PDUFA) goal date of June 16, 2023.

About CAMZYOS (mavacamten)

CAMZYOS (mavacamten) is the first and only cardiac myosin inhibitor approved in the U.S., indicated for the treatment of adults with symptomatic New York Heart Association (NYHA) class II-III obstructive hypertrophic cardiomyopathy (HCM) to improve functional capacity and symptoms. It has also received regulatory approvals in Australia, Canada, Brazil and Switzerland. CAMZYOS is an allosteric and reversible inhibitor selective for cardiac myosin. CAMZYOS modulates the number of myosin heads that can enter “on actin” (power-generating) states, thus reducing the probability of force-producing (systolic) and residual (diastolic) cross-bridge formation. Excess myosin actin cross-bridge formation and dysregulation of the super-relaxed state are mechanistic hallmarks of HCM. CAMZYOS shifts the overall myosin population towards an energy-sparing, recruitable, super-relaxed state. In HCM patients, myosin inhibition with CAMZYOS reduces dynamic LVOT obstruction and improves cardiac filling pressures.

About CAMZYOS REMS Program

CAMZYOS is only available in the U.S. through a restricted program called the CAMZYOS REMS Program because of the risk of heart failure due to systolic dysfunction. Further information is available at www.CAMZYOSREMS.com or by telephone at 1-833-628-7367.

U.S. INDICATION

CAMZYOS(mavacamten) is indicated for the treatment of adults with symptomatic New York Heart Association (NYHA) class II-III obstructive hypertrophic cardiomyopathy (HCM) to improve functional capacity and symptoms.

IMPORTANT SAFETY INFORMATION

WARNING: RISK OF HEART FAILURE

CAMZYOS reduces left ventricular ejection fraction (LVEF) and can cause heart failure due to systolic dysfunction.

Echocardiogram assessments of LVEF are required prior to and during treatment with CAMZYOS. Initiation of CAMZYOS in patients with LVEF