U.S. Full Prescribing Information, including Boxed WARNING

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VALOR-HCM Primary Composite Endpoint

For SRT-eligible patients with NYHA class II–III obstructive HCM,

CAMZYOS® Demonstrated Significant Benefit vs Placebo in a Second Phase 3 Clinical Trial1

18% (n=10/56) of patients taking CAMZYOS and 77% (n=43/56) taking placebo met the primary composite endpoint (remained guideline-eligible for SRT at Week 16 or chose to undergo SRT at or before Week 16). Two patients in each group decided to proceed with SRT.1

Treatment difference (95% CI):
59% (44, 74);
P<0.0001

Patients no longer guideline eligible and did not choose to undergo SRT at Week 161,2

Percentage of Patients who were Guideline-eligible for SRT and did not Undergo SRT Chart Percentage of Patients who were Guideline-eligible for SRT and did not Undergo SRT Chart

At baseline, 95% of patients were on background therapy (BB, CCB, or disopyramide either as monotherapy or in combination).2

  • *The primary composite endpoint is based on the investigator’s guideline-based recommendation for SRT. Patients who undergo SRT, terminate early, die, or cannot otherwise be assessed for SRT eligibility at the end of the 16-week, placebo-controlled treatment period will also be classified as meeting the primary composite endpoint.3

BB=beta blocker; CCB=calcium channel blocker; CI=confidence interval; HCM=hypertrophic cardiomyopathy; NYHA=New York Heart Association; SRT=septal reduction therapy.

The efficacy of CAMZYOS was evaluated in VALOR-HCM, a phase 3, double-blind, randomized, placebo-controlled trial in 112 adult patients with severely symptomatic drug-refractory obstructive HCM, and NYHA class III–IV or class II with exertional syncope or near syncope. Patients were randomized in a 1:1 ratio to receive a starting dose of 5 mg of CAMZYOS (n=56) or placebo (n=56) once daily for 16 weeks. Dosage was monitored and adjusted at Weeks 8 and 12 to optimize patient response (decrease in LVOT gradient with Valsalva) and maintain LVEF ≥50%.1,2

Select Important Safety Information

ADVERSE REACTIONS
Based on the safety profile from the pivotal EXPLORER-HCM trial, there were no new adverse reactions identified in VALOR-HCM. See EXPLORER-HCM safety.

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Important Safety
Information
WARNING: RISK OF HEART FAILURE

CAMZYOSTM (mavacamten) 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 <55% is not recommended. Interrupt CAMZYOS if LVEF is <50% at any visit or if the patient experiences heart failure symptoms or worsening clinical status.

Concomitant use of CAMZYOS with certain cytochrome P450 inhibitors or discontinuation of certain cytochrome P450 inducers may increase the risk of heart failure due to systolic dysfunction; therefore, the use of CAMZYOS is contraindicated with the following:

  • Moderate to strong CYP2C19 inhibitors or strong CYP3A4 inhibitors
  • Moderate to strong CYP2C19 inducers or moderate to strong CYP3A4 inducers

Because of the risk of heart failure due to systolic dysfunction, CAMZYOS is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the CAMZYOS REMS PROGRAM.

CONTRAINDICATIONS

CAMZYOS is contraindicated with concomitant use of:

  • Moderate to strong CYP2C19 inhibitors or strong CYP3A4 inhibitors
  • Moderate to strong CYP2C19 inducers or moderate to strong CYP3A4 inducers
WARNINGS AND PRECAUTIONS

Heart Failure

CAMZYOS reduces systolic contraction and can cause heart failure or totally block ventricular function. Patients who experience a serious intercurrent illness (e.g., serious infection) or arrhythmia (e.g., atrial fibrillation or other uncontrolled tachyarrhythmia) are at greater risk of developing systolic dysfunction and heart failure.

Assess the patient’s clinical status and LVEF prior to and regularly during treatment and adjust the CAMZYOS dose accordingly. New or worsening arrhythmia, dyspnea, chest pain, fatigue, palpitations, leg edema, or elevations in N-terminal pro-B-type natriuretic peptide (NT-proBNP) may be signs and symptoms of heart failure and should also prompt an evaluation of cardiac function.

Asymptomatic LVEF reduction, intercurrent illnesses, and arrhythmias require additional dosing considerations.

Initiation of CAMZYOS in patients with LVEF <55% is not recommended. Avoid concomitant use of CAMZYOS in patients on disopyramide, ranolazine, verapamil with a beta blocker, or diltiazem with a beta blocker as these medications and combinations increase the risk of left ventricular systolic dysfunction and heart failure symptoms and clinical experience is limited.

CYP 450 Drug Interactions Leading to Heart Failure or Loss of Effectiveness

CAMZYOS is primarily metabolized by CYP2C19 and CYP3A4 enzymes. Concomitant use of CAMZYOS and drugs that interact with these enzymes may lead to life-threatening drug interactions such as heart failure or loss of effectiveness.

Advise patients of the potential for drug interactions, including with over-the-counter medications (such as omeprazole, esomeprazole, or cimetidine). Advise patients to inform their healthcare provider of all concomitant products prior to and during CAMZYOS treatment.

CAMZYOS Risk Evaluation and Mitigation Strategy (REMS) Program

CAMZYOS is only available through a restricted program called the CAMZYOS REMS Program because of the risk of heart failure due to systolic dysfunction. Notable requirements of the CAMZYOS REMS Program include the following:

  • Prescribers must be certified by enrolling in the REMS Program.
  • Patients must enroll in the REMS Program and comply with ongoing monitoring requirements.
  • Pharmacies must be certified by enrolling in the REMS Program and must only dispense to patients who are authorized to receive CAMZYOS.
  • Wholesalers and distributors must only distribute to certified pharmacies.

Further information is available at www.CAMZYOSREMS.com or by telephone at 1-833-628-7367.

Embryo-Fetal Toxicity

CAMZYOS may cause fetal toxicity when administered to a pregnant female, based on animal studies. Confirm absence of pregnancy in females of reproductive potential prior to treatment and advise patients to use effective contraception during treatment with CAMZYOS and for 4 months after the last dose. CAMZYOS may reduce the effectiveness of combined hormonal contraceptives (CHCs). Advise patients using CHCs to use an alternative contraceptive method that is not affected by CYP 450 enzyme induction or to add nonhormonal contraception. Advise females of reproductive potential about the potential risk to the fetus with maternal exposure to CAMZYOS during pregnancy.

ADVERSE REACTIONS

In the EXPLORER-HCM trial, adverse reactions occurring in >5% of patients and more commonly in the CAMZYOS group than in the placebo group were dizziness (27% vs 18%) and syncope (6% vs 2%). There were no new adverse reactions identified in VALOR-HCM.

Effects on Systolic Function

In the EXPLORER-HCM trial, mean (SD) resting LVEF was 74% (6) at baseline in both treatment groups. Mean (SD) absolute change from baseline in LVEF was -4% (8) in the CAMZYOS group and 0% (7) in the placebo group over the 30-week treatment period. At Week 38, following an 8-week interruption of trial drug, mean LVEF was similar to baseline for both treatment groups. In the EXPLORER-HCM trial, 7 (6%) patients in the CAMZYOS group and 2 (2%) patients in the placebo group experienced reversible reductions in LVEF <50% (median 48%: range 35-49%) while on treatment. In all 7 patients treated with CAMZYOS, LVEF recovered following interruption of CAMZYOS.

DRUG INTERACTIONS

Potential for Other Drugs to Affect Plasma Concentrations of CAMZYOS

CAMZYOS is primarily metabolized by CYP2C19 and to a lesser extent by CYP3A4 and CYP2C9. Inducers and inhibitors of CYP2C19 and moderate to strong inhibitors or inducers of CYP3A4 may affect the exposures of CAMZYOS.

Impact of Other Drugs on CAMZYOS:

  • Moderate to Strong CYP2C19 Inhibitors or Strong CYP3A4 Inhibitors: Concomitant use increases CAMZYOS exposure, which may increase the risk of heart failure due to systolic dysfunction. Concomitant use is contraindicated.
  • Moderate to Strong CYP2C19 Inducers or Moderate to Strong CYP3A4 Inducers: Concomitant use decreases CAMZYOS exposure, which may reduce CAMZYOS’ efficacy. The risk of heart failure due to systolic dysfunction may increase with discontinuation of these inducers as the levels of induced enzyme normalizes. Concomitant use is contraindicated.
  • Weak CYP2C19 Inhibitors or Moderate CYP3A4 Inhibitors: Concomitant use with a weak CYP2C19 inhibitor or a moderate CYP3A4 inhibitor increases CAMZYOS exposure, which may increase the risk of adverse drug reactions. Initiate CAMZYOS at the recommended starting dose of 5 mg orally once daily in patients who are on stable therapy with a weak CYP2C19 inhibitor or a moderate CYP3A4 inhibitor. Reduce dose of CAMZYOS by one level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients who are on CAMZYOS treatment and intend to initiate a weak CYP2C19 inhibitor or a moderate CYP3A4 inhibitor. Schedule clinical and echocardiographic assessment 4 weeks after inhibitor initiation, and do not up-titrate CAMZYOS until 12 weeks after inhibitor initiation. Avoid initiation of concomitant weak CYP2C19 and moderate CYP3A4 inhibitors in patients who are on stable treatment with 2.5 mg of CAMZYOS because a lower dose is not available.

Potential for CAMZYOS to Affect Plasma Concentrations of Other Drugs

CAMZYOS is an inducer of CYP3A4, CYP2C9, and CYP2C19. Concomitant use with CYP3A4, CYP2C19, or CYP2C9 substrates may reduce plasma concentration of these drugs. Closely monitor when CAMZYOS is used in combination with CYP3A4, CYP2C19, or CYP2C9 substrates where decreases in the plasma concentration of these drugs may reduce their activity.

Hormonal Contraceptives: Progestin and ethinyl estradiol are CYP3A4 substrates. Concomitant use of CAMZYOS may decrease exposures of ethinyl estradiol and progestin, which may lead to contraceptive failure or an increase in breakthrough bleeding. Advise patients to use a contraceptive method that is not affected by CYP 450 enzyme induction (e.g., intrauterine system) or add nonhormonal contraception (such as condoms) during concomitant use and for 4 months after the last dose of CAMZYOS.

Drugs That Reduce Cardiac Contractility

Expect additive negative inotropic effects of CAMZYOS and other drugs that reduce cardiac contractility. Avoid concomitant use of CAMZYOS in patients on disopyramide, ranolazine, verapamil with a beta blocker, or diltiazem with a beta blocker as these medications and combinations increase the risk of left ventricular systolic dysfunction and heart failure symptoms and clinical experience is limited.

If concomitant therapy with a negative inotrope is initiated, or if the dose of a negative inotrope is increased, monitor LVEF closely until stable doses and clinical response have been achieved.

SPECIFIC POPULATIONS

Pregnancy

CAMZYOS may cause fetal harm when administered to a pregnant female. Advise pregnant females about the potential risk to the fetus with maternal exposure to CAMZYOS during pregnancy. There is a pregnancy safety study for CAMZYOS. If CAMZYOS is administered during pregnancy, or if a patient becomes pregnant while receiving CAMZYOS or within 4 months after the last dose of CAMZYOS, healthcare providers should report CAMZYOS exposure by contacting Bristol Myers Squibb at 1-800-721-5072 or www.bms.com.

Lactation

The presence of CAMZYOS in human or animal milk, the drug’s effects on the breastfed infant, or the effects on milk production are unknown. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for CAMZYOS and any potential adverse effects on the breastfed child from CAMZYOS or from the underlying maternal condition.

Females and Males of Reproductive Potential

Confirm absence of pregnancy in females of reproductive potential prior to initiation of CAMZYOS. Advise females of reproductive potential to use effective contraception during treatment with CAMZYOS and for 4 months after the last dose. Use of CAMZYOS may reduce the effectiveness of CHCs. Advise patients using CHCs to use an alternative contraceptive method or add nonhormonal contraception.

INDICATION

CAMZYOS 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.

CAMZYOS is available in 2.5 mg, 5 mg, 10 mg, and 15 mg capsules.

Please see U.S. Full Prescribing Information, including Boxed WARNING.

References:

  1. CAMZYOS [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2023.
  2. Desai MY, Owens A, Geske JB, et al. Myosin inhibition in patients with obstructive hypertrophic cardiomyopathy referred for septal reduction therapy. J Am Coll Cardiol. 2022;80(2):95-108.
  3. Desai MY, Wolski K, Owens A, et al. Study design and rationale of VALOR-HCM: evaluation of mavacamten in adults with symptomatic obstructive hypertrophic cardiomyopathy who are eligible for septal reduction therapy. Am Heart J. 2021;239:80-89.
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References:

  1. CAMZYOS [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2023.
  2. Desai MY, Owens A, Geske JB, et al. Myosin inhibition in patients with obstructive hypertrophic cardiomyopathy referred for septal reduction therapy. J Am Coll Cardiol. 2022;80(2):95-108.
  3. Desai MY, Wolski K, Owens A, et al. Study design and rationale of VALOR-HCM: evaluation of mavacamten in adults with symptomatic obstructive hypertrophic cardiomyopathy who are eligible for septal reduction therapy. Am Heart J. 2021;239:80-89.
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