U.S. Full Prescribing Information, including Boxed WARNING

Request a Rep
Request a Rep

For patients with NYHA class II–III obstructive HCM,

In EXPLORER-LTE, CAMZYOS® Consistently Reduced Obstruction, and Improved Symptoms (NYHA Class) Through ~3.5 Years1

Study Design > See Select Safety Profile >

EXPLORER-HCM Primary Endpoint

PRIMARY ENDPOINT3 The primary composite functional endpoint was defined as an improvement of pVO2 by 1.5 mL/kg/min or more and improvement in NYHA class by at least 1 or an improvement of pVO2 by 3.0 mL/kg/min or more and no worsening in NYHA class. At Week 30, 37% (n=45/123) of patients taking CAMZYOS met the primary composite functional endpoint vs 17% taking placebo. The treatment difference was 19% (95% CI: 9, 30; P=0.0005).

EXPLORER-LTE: Primary Objective–Safety and Tolerability

In the pivotal EXPLORER-HCM trial, adverse reactions occurring in >5% of patients and more commonly in the CAMZYOS group were dizziness (27% vs 18%) and syncope (6% vs 2%).2

See ~3.5 years (180 weeks) of follow-up safety data for CAMZYOS >

EXPLORER-LTE: LVOT Obstruction

In the pivotal EXPLORER-HCM trial, -49 (34) mmHg mean change (SD) in Valsalva LVOT gradient with CAMZYOS (n=123) vs -12 (31) mmHg with placebo (n=128) from baseline to Week 30.2

Interim analysis from EXPLORER-LTE

CAMZYOS Demonstrated Consistent and Sustained Reductions in Mean Valsalva LVOT Gradient to Week 1801

Exploratory objective (interim data): Mean Valsalva LVOT gradient from baseline* to Week 1801,2

Mean Valsalva LVOT Gradient from Baseline to Week 180 Chart
Mean Valsalva LVOT Gradient from Baseline to Week 180 Chart Mean Valsalva LVOT Gradient from Baseline to Week 180 Chart

Swipe left for full chart

While this exploratory endpoint was prespecified, it was not powered for significance

Important LVOT gradient thresholds3:

  • A resting or provoked LVOT gradient of ≥50 mmHg is the obstructive criteria for SRT in patients with drug-refractory symptoms.1,3

Additional EXPLORER-LTE LVOT data1:

  • An LVOT peak gradient of ≥30 mmHg is indicative of obstruction
  • Overall, 83% (n=191) of patients achieved a reduced Valsalva LVOT gradient of ≤30 mmHg, or below obstructive levels at the time of analysis (data cutoff)
  • *Baseline is defined as last non-missing measurement before the first dose of CAMZYOS in MAVA- LTE.1
  • †Based on the results of the 91 patients who have reached Week 180.1
  • LVOT=left ventricular outflow tract; SRT=septal reduction therapy.

Interim analysis from EXPLORER-LTE

Overall, ~83% of Patients No Longer Had Obstruction‡ at the Time of Analysis (Data Cutoff; n=191)1,3§

Proportion of patients who achieved a Valsalva LVOT gradient of ≤30 mmHg by visit1,3

Proportion of Patients Who No Longer Had Obstruction at Time of Analysis Chart Proportion of Patients Who No Longer Had Obstruction at Time of Analysis Chart

Swipe left for full chart

This exploratory endpoint was derived from a post-hoc analysis and was not powered for significance.

  • ‡Based on the AHA/Multisociety Guideline for HCM, obstruction is considered present if peak LVOT gradient is ≥30 mmHg.3
  • §Centrally read.1

EXPLORER-LTE: NYHA Class

In the pivotal EXPLORER-HCM trial, 65% of patients (n=80/123) taking CAMZYOS improved by ≥1 NYHA class vs 31% (n=40/128) taking placebo from baseline to Week 30. Approximately 73% of the randomized patients were NYHA class II and 27% were NYHA class III at baseline.3

Interim analysis from EXPLORER-LTE

~78% of Patients Improved by ≥1 NYHA Class From Baseline to Week 1801||

Secondary objective: Proportion of patients with at least 1 NYHA class improvement from baseline to Week 180 (n=95)1

NYHA Class improvement with CAMZYOS® (mavacamten) in Explorer-LTE NYHA Class improvement with CAMZYOS® (mavacamten) in Explorer-LTE

While this endpoint was prespecified, it was not powered for significance.

Of the patients (n=95) at the Week 180 visit1:

  • 63 patients (66%) were NYHA Class I
  • 29 patients (31%) were NYHA Class II
  • 3 patients (3%) were NYHA Class III

Additional EXPLORER-LTE NYHA class data1:

  • One patient worsened from NYHA Class II to NYHA Class III at Week 180 and had ongoing atrial fibrillation unrelated to CAMZYOS during this time
  • ||Time points for NYHA functional class assessments included Weeks 12, 48, 108, 120, 132, 144, 156, and 180 as per the trial protocol.
  • Baseline is defined as last non-missing measurement before the first dose of CAMZYOS in MAVA-LTE.
  • #Percentage of patients who achieved improvement of ≥2 classes were also included in the percentage of those who improved by ≥1 class.

NYHA class distribution over time1

NYHA Class Distribution from Baseline to Week 180 Graphic NYHA Class Distribution from Baseline to Week 180 Graphic

While this exploratory endpoint was prespecified, it was not powered for significance.

EXPLORER-LTE: Cardiac Biomarker

In the pivotal EXPLORER-HCM trial, the proportion of geometric mean ratio of NT-proBNP between the CAMZYOS group and placebo group was 0.20 (95% CI: 0.17, 0.24) from baseline to Week 30.2

Interim analysis from EXPLORER-LTE

Normalized NT-proBNP Observed in More Than Half of Patients on CAMZYOS at Week 1801

Exploratory objective (interim data): Median NT-proBNP from baseline** to Week 1801

Median Change in NT-proBNP from Baseline to Week 180 Chart
Median Change in NT-proBNP from Baseline to Week 180 Chart Median Change in NT-proBNP from Baseline to Week 180 Chart

Swipe left for full chart

While this exploratory endpoint was prespecified, it was not powered for significance. The clinical significance of the NT-proBNP findings is unknown.1

  • At baseline, ~10% (n=22/230) of patients presented with a NTproBNP concentration of <124 ng/L, indicative of normal range1
  • The proportion of patients with NT-proBNP levels in the normal range increased to ~28% at Week 4 (n=62/218), and ~54% at Week 180 (n=50/93)1
  • At Week 180, the median (IQR) plasma concentration of NT-proBNP was 118 (58, 304) ng/L1

**Baseline is defined as last non-missing measurement before the first dose of CAMZYOS in MAVA-LTE.1

EXPLORER-LTE: Cardiac Structure

In the pivotal EXPLORER-HCM trial, the mean (SD) reduction from baseline in left atrial volume index (LAVI) in the CAMZYOS group (-7.5 [7.8] mL/m2) versus no change in the placebo group (-0.1 [8.7] mL/m2).2

Interim analysis from EXPLORER-LTE

Changes in LAVI Over the 180 Week Treatment Period With CAMZYOS1,5

Exploratory objective (interim data): Mean LAVI from baseline†† to Week 1801,5

Mean LAVI from Baseline to Week 180 Chart Mean LAVI from Baseline to Week 180 Chart
Mean LAVI from Baseline to Week 180 Chart

While this exploratory endpoint was prespecified, it was not powered for significance. The clinical significance of the LAVI findings is unknown.1

††Baseline is defined as last non-missing measurement before the first dose of CAMZYOS in MAVA-LTE.1

The EXPLORER-LTE cohort of the MAVA-LTE trial sought to evaluate the safety and efficacy of CAMZYOS starting at 5 mg in adults who had completed the EXPLORER-HCM trial.* The EXPLORER-LTE cohort (n=231) is a single-arm study without an active comparator.1,5,6

Dose adjustments could be made at Weeks 4, 8, 12, and during subsequent visits based on the patient’s Valsalva LVOT gradient and LVEF, except for Week 24, in which the patient’s stress TTE was used.† Unscheduled dose adjustments could occur at Week 24 and every 12 weeks thereafter. Treatment was temporarily interrupted if LVEF <50%. Mean time from EXPLORER-HCM end of study to Day 1 of EXPLORER-LTE was 66.5 days (range: 3-359 days).1,5,6

  • *Patients enrolled in EXPLORER-LTE were part of either the CAMZYOS or placebo arm in the EXPLORER-HCM trial.1,5,6
  • †This is not consistent with the current approved dosing schedule per the U.S. Full Prescribing Information.2
Read the EXPLORER-LTE reprint >
See EXPLORER-LTE
Select Safety Data

3500-US-2400470  12/24

This website is best viewed
using the horizontal display
on your tablet device.

This website is best viewed
using the vertical display
on your mobile device.

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. CHCs containing a combination of ethinyl estradiol and norethindrone may be used with CAMZYOS. However, CAMZYOS may reduce the effectiveness of certain other combined hormonal contraceptives (CHC). If these CHCs are used, advise patients to add nonhormonal contraception (such as condoms) during concomitant use and for 4 months after the last dose of CAMZYOS.

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, CYP2C9, or CYP2C19 substrates may reduce plasma concentration of these drugs. Closely monitor when CAMZYOS is used with concomitant CYP3A4, CYP2C9, or CYP2C19 substrates unless otherwise recommended in the Prescribing Information.

Certain Combined Hormonal Contraceptives (CHC): Progestin and ethinyl estradiol are CYP3A4 substrates. Concomitant use of CAMZYOS may decrease exposures of certain progestins, which may lead to contraceptive failure. CHCs containing a combination of ethinyl estradiol and norethindrone may be used with CAMZYOS, but if other CHCs are used, advise patients to add nonhormonal contraception (such as condoms) during concomitant use and 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. CHCs containing a combination of ethinyl estradiol and norethindrone may be used with CAMZYOS. However, CAMZYOS may reduce the effectiveness of certain other combined hormonal contraceptives (CHC). If these CHCs are used, advise patients to add nonhormonal contraception (such as condoms) during concomitant use and for 4 months after the last dose of CAMZYOS.

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.

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

Please see US Full Prescribing Information, including Boxed WARNING.

References:

  1. Garcia-Pavia P, Oreziak A, Masri A, et al. Long-term effect of mavacamten in obstructive hypertrophic cardiomyopathy. 2024; ehae579. doi:10.1093/eurheartj/ehae579
  2. CAMZYOS. [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2024.
  3. Ommen SR, Ho CY, Asif IM, et al. 2024 AHA/ACC/AMSSM/HRS/PACES/SCMR guideline for the management of hypertrophic cardiomyopathy: a report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. Circulation. 2024;149(23):e1239-e1311. doi:10.1161/CIR.0000000000001250
  4. Data on file. Princeton, NJ: Bristol-Myers Squibb Company; 2024.
  5. Garcia-Pavia P, Oreziak A, Masri A, et al. Long-term safety and efficacy of mavacamten in obstructive hypertrophic cardiomyopathy: up to 3.5-year follow-up results of the EXPLORER cohort of MAVA-Long-Term Extension study. Presented at European Society of Cardiology; August 30-September 2, 2024; London and online. Oral presentation 84470.
  6. 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.
Back to Top IconBack to Top IconBack to top

References:

  1. Garcia-Pavia P, Oreziak A, Masri A, et al. Long-term effect of mavacamten in obstructive hypertrophic cardiomyopathy. 2024; ehae579. doi:10.1093/eurheartj/ehae579
  2. CAMZYOS. [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2024.
  3. Ommen SR, Ho CY, Asif IM, et al. 2024 AHA/ACC/AMSSM/HRS/PACES/SCMR guideline for the management of hypertrophic cardiomyopathy: a report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. Circulation. 2024;149(23):e1239-e1311. doi:10.1161/CIR.0000000000001250
  4. Data on file. Princeton, NJ: Bristol-Myers Squibb Company; 2024.
  5. Garcia-Pavia P, Oreziak A, Masri A, et al. Long-term safety and efficacy of mavacamten in obstructive hypertrophic cardiomyopathy: up to 3.5-year follow-up results of the EXPLORER cohort of MAVA-Long-Term Extension study. Presented at European Society of Cardiology; August 30-September 2, 2024; London and online. Oral presentation 84470.
  6. 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.
Back to Top IconBack to Top IconBack to top