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U.S. Full Prescribing Information, including Boxed WARNING

For patients with NYHA class II–III
obstructive HCM,

Primary composite functional endpoint

To achieve the primary composite functional endpoint, patients needed to achieve either ≥1 NYHA class improvement and an increase of ≥1.5 mL/kg/min in peak oxygen consumption (pVO2) or no worsening NYHA class and an increase of ≥3.0 mL/kg/min in pVO2.1,2

At week 30, 37% (n=45/123) of patients taking CAMZYOS® achieved the primary composite functional endpoint vs 17% (n=22/128) with placebo (95% CI: 9, 30; P=0.0005).1,2

Secondary endpoint: mean change in post-exercise LVOT peak gradient
from baseline to week 301,2

CAMZYOS
Significantly
Reduced LVOT
Obstruction vs
Placebo1,2

LVOT obstruction was assessed by post-exercise LVOT peak gradient. Treatment difference (95% CI): -35 mmHg (-43, -28);P<0.0001
Secondary Endpoint LVOT Mean Change CAMZYOS® (mavacamten) vs Placebo, Chart Secondary Endpoint LVOT Mean Change CAMZYOS® (mavacamten) vs Placebo, Chart

Guideline-based threshold for surgery consideration (>50 mmHg)2

Guideline-based diagnostic criteria for obstruction (>30 mmHg)2

Data based on all randomized patients who received ≥1 dose of study treatment. LVOT gradient was analyzed with all available data without imputation.2

CI=confidence interval; LVOT=left ventricular outflow tract obstruction; SD=standard deviation.

The efficacy of CAMZYOS was evaluated in EXPLORER-HCM, a phase 3, double-blind, randomized, placebo-controlled trial that enrolled 251 adult patients with symptomatic (New York Heart Association [NYHA] class II and III) obstructive HCM, with left ventricular outflow tract (LVOT) peak gradient ≥50 mmHg, and left ventricle ejection fraction (LVEF) ≥55% at rest or with provocation.1 Patients were randomized in a 1:1 ratio to receive CAMZYOS (n=123) or placebo (n=128) once daily for 30 weeks.1

All subjects were initiated on CAMZYOS 5 mg (or matching placebo) once daily, and the dose was periodically adjusted to optimize patient response (decrease in LVOT gradient with Valsalva maneuver), maintain LVEF ≥50%, and was further informed by plasma concentrations of CAMZYOS.1,2

Select Important Safety Information

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%).
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.

Please see additional Important Safety Information below, including Boxed WARNING.

Prespecified exploratory analysis of post-exercise LVOT gradient

Exploratory endpoints: proportion of patients achieving post-exercise LVOT peak gradient <50 mmHg or <30 mmHg at week 302

74% (n=75/101) of patients on CAMZYOS had
a post-exercise LVOT gradient <50 mmHg
and 21% (n=22/106) in the placebo arm2*

57% (n=64/113) of patients on CAMZYOS had
a post-exercise LVOT gradient <30 mmHg
and 7% (n=8/114) in the placebo arm2†

While these exploratory endpoints were prespecified, they were not powered for significance.3

  • *Only patients with baseline post-exercise LVOT peak gradient of at least 50 mmHg were assessed.2
  • †Only patients with baseline post-exercise LVOT peak gradient of at least 30 mmHg were assessed.2
Select Important Safety Information

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%).
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.

Please see additional Important Safety Information below, including Boxed WARNING.

Read the EXPLORER-HCM reprint >
Secondary endpoint: peak
oxygen consumption

For patients with NYHA class II–III
obstructive HCM,

Primary composite functional endpoint

To achieve the primary composite functional endpoint, patients needed to achieve either ≥1 NYHA class improvement and an increase of ≥1.5 mL/kg/min in peak oxygen consumption (pVO2) or no worsening NYHA class and an increase of ≥3.0 mL/kg/min in pVO2.1,2

At week 30, 37% (n=45/123) of patients taking CAMZYOS® achieved the primary composite functional endpoint vs 17% (n=22/128) with placebo (95% CI: 9, 30; P=0.0005).1,2

Secondary endpoint: mean change in pVO2 consumption from baseline
to week 301,2

Significant Improvement in pVO2 in Patients Receiving CAMZYOS vs Placebo1,2

Treatment difference (95% CI): 1.4 (0.6, 2.1); P<0.0006
Secondary Endpoint pVO2 Consumption Mean Change CAMZYOS® (mavacamten) vs Placebo, Chart Secondary Endpoint pVO2 Consumption Mean Change CAMZYOS® (mavacamten) vs Placebo, Chart

Mean change in pVO2 from baseline to week 30 was 1.4 mL/kg/min (SD, 3.1) for patients taking CAMZYOS and -0.1 mL/kg/min (SD, 3.0) for patients taking placebo.1

pVO2 measures peak oxygen consumption during cardiopulmonary exercise testing. Data based on all randomized patients who received ≥1 dose of study treatment.2,3

  • Data based on all randomized patients who received ≥1 dose of study treatment.2

CI=confidence interval; SD=standard deviation.

The efficacy of CAMZYOS was evaluated in EXPLORER-HCM, a phase 3, double-blind, randomized, placebo-controlled trial that enrolled 251 adult patients with symptomatic (New York Heart Association [NYHA] class II and III) obstructive HCM, with left ventricular outflow tract (LVOT) peak gradient ≥50 mmHg, and left ventricle ejection fraction (LVEF) ≥55% at rest or with provocation.1 Patients were randomized in a 1:1 ratio to receive CAMZYOS (n=123) or placebo (n=128) once daily for 30 weeks.1

All subjects were initiated on CAMZYOS 5 mg (or matching placebo) once daily, and the dose was periodically adjusted to optimize patient response (decrease in LVOT gradient with Valsalva maneuver), maintain LVEF ≥50%, and was further informed by plasma concentrations of CAMZYOS.1,2

Select Important Safety Information

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%).
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.

Please see additional Important Safety Information below, including Boxed WARNING.

Read the EXPLORER-HCM reprint >
Secondary endpoint:
NYHA class

For patients with NYHA class II–III
obstructive HCM,

Primary composite functional endpoint

To achieve the primary composite functional endpoint, patients needed to achieve either ≥1 NYHA class improvement and an increase of ≥1.5 mL/kg/min in peak oxygen consumption (pVO2) or no worsening NYHA class and an increase of ≥3.0 mL/kg/min in pVO2.1,2

At week 30, 37% (n=45/123) of patients taking CAMZYOS® achieved the primary composite functional endpoint vs 17% (n=22/128) with placebo (95% CI: 9, 30; P=0.0005).1,2

Secondary endpoint: proportion of patients with ≥1 NYHA class improvement from baseline to week 301,2

Significantly More Patients Improved by ≥1 NYHA Class With CAMZYOS vs Placebo1,2

Treatment difference (95% CI): 34% (22, 45); P=0.0001

At baseline, approximately 73% of the randomized patients were NYHA class II and 27% were NYHA class III.1

Data based on all randomized patients who received ≥1 dose of study treatment. Missing NYHA class data at week 30 were imputed with the week 26 value for NYHA response. Patients with a nonevaluable NYHA secondary endpoint were considered nonresponders.2

The efficacy of CAMZYOS was evaluated in EXPLORER-HCM, a phase 3, double-blind, randomized, placebo-controlled trial that enrolled 251 adult patients with symptomatic (New York Heart Association [NYHA] class II and III) obstructive HCM, with left ventricular outflow tract (LVOT) peak gradient ≥50 mmHg, and left ventricle ejection fraction (LVEF) ≥55% at rest or with provocation.1 Patients were randomized in a 1:1 ratio to receive CAMZYOS (n=123) or placebo (n=128) once daily for 30 weeks.1

All subjects were initiated on CAMZYOS 5 mg (or matching placebo) once daily, and the dose was periodically adjusted to optimize patient response (decrease in LVOT gradient with Valsalva maneuver), maintain LVEF ≥50%, and was further informed by plasma concentrations of CAMZYOS.1,2

Select Important Safety Information

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%).
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.

Please see additional Important Safety Information below, including Boxed WARNING.

NYHA class changes from baseline to week 30 in CAMZYOS and placebo2

The data below were used to calculate the secondary endpoint related to NYHA class but were exploratory in nature and not evaluated for significance to compare between the treatment groups.2,3

Data used to Calculate Secondary Endpoint NYHA Class Changes CAMZYOS® (mavacamten) vs Placebo, Chart Data used to Calculate Secondary Endpoint NYHA Class Changes CAMZYOS® (mavacamten) vs Placebo, Chart

CI=confidence interval; NYHA=New York Heart Association.

Select Important Safety Information

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%).
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.

Please see additional Important Safety Information below, including Boxed WARNING.

Read the EXPLORER-HCM reprint >
Secondary endpoint:
KCCQ-23–CSS and HCMSQ-SoB

For patients with NYHA class II–III
obstructive HCM,

Primary composite functional endpoint

To achieve the primary composite functional endpoint, patients needed to achieve either ≥1 NYHA class improvement and an increase of ≥1.5 mL/kg/min in peak oxygen consumption (pVO2) or no worsening NYHA class and an increase of ≥3.0 mL/kg/min in pVO2.1,2

At week 30, 37% (n=45/123) of patients taking CAMZYOS® achieved the primary composite functional endpoint vs 17% (n=22/128) with placebo (95% CI: 9, 30; P=0.0005).1,2

KCCQ-23–CSS and HCMSQ-SoB With CAMZYOS and Placebo1,2

Secondary endpoint: mean change in KCCQ-23–CSS from baseline to week 301,2

CAMZYOS showed significant mean improvement in KCCQ-23–CSS score (patient-reported symptom burden and physical limitations) vs placebo1,2


Treatment difference (95% CI): 9 (5, 13); P<0.0001
KCCQ-23 clinical–summary score: mean change from baseline over time1
Secondary Endpoint KCCQ-23 Clinical Summary Mean Change CAMZYOS® (mavacamten) vs Placebo, Chart Secondary Endpoint KCCQ-23 Clinical Summary Mean Change CAMZYOS® (mavacamten) vs Placebo, Chart

Mean baseline KCCQ-23 CSS (SD) was 71 (16) for the CAMZYOS group (n=99) and 71 (19) for the placebo group (n=97).1

KCCQ-23 TSS: change from baseline to week 30, mean (SD) was 12 (15) for CAMZYOS and 5 (16) for placebo.1

KCCQ-23 PL: change from baseline to week 30, mean (SD) was 15 (17) for CAMZYOS and 4 (15) for placebo.1

The KCCQ-23–CSS is composed of the physical limitations and total symptom burden scores of the KCCQ-23. The Clinical Summary Score ranges from 0 to 100, with higher scores representing less severe symptoms and/or physical limitations.1

Missing data were not imputed to summarize the baseline and change from baseline to week 30 values. Difference in mean change from baseline between treatment groups was estimated using a mixed model for repeated measures.1

Patient-reported outcomes were analyzed with all available data. Sensitivity analyses were conducted to assess the effect of the missing data. When missing data were imputed with unfavorable results for the CAMZYOS group, the estimated treatment effects of KCCQ-CSS remained significant (P<0.05).2

KCCQ-23–CSS=Kansas City Cardiomyopathy Questionnaire (23-item version)–Clinical Summary Score; LS=least squares; PL=physical limitations; SD=standard deviation; SE=standard error; TSS=total symptom score.

The Kansas City Cardiomyopathy Questionnaire (KCCQ) has been used to capture and quantify patient-reported outcomes in a disease-specific fashion.3

The efficacy of CAMZYOS was evaluated in EXPLORER-HCM, a phase 3, double-blind, randomized, placebo-controlled trial that enrolled 251 adult patients with symptomatic (New York Heart Association [NYHA] class II and III) obstructive HCM, with left ventricular outflow tract (LVOT) peak gradient ≥50 mmHg, and left ventricle ejection fraction (LVEF) ≥55% at rest or with provocation.1 Patients were randomized in a 1:1 ratio to receive CAMZYOS (n=123) or placebo (n=128) once daily for 30 weeks.1

All subjects were initiated on CAMZYOS 5 mg (or matching placebo) once daily, and the dose was periodically adjusted to optimize patient response (decrease in LVOT gradient with Valsalva maneuver), maintain LVEF ≥50%, and was further informed by plasma concentrations of CAMZYOS.1,2

Select Important Safety Information

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%).
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.

Please see additional Important Safety Information below, including Boxed WARNING.

Secondary endpoint: mean change in HCMSQ-SoB from baseline to
week 301,2

CAMZYOS showed significant mean improvement in HCMSQ-SoB (patient-reported frequency and severity of shortness of breath) vs placebo1,2

Treatment difference: -2 (-2, -1); P<0.0001

HCMSQ shortness of breath domain: mean change from baseline over time1

Exploratory Endpoint HCMSQ-SoB Mean Change CAMZYOS® (mavacamten) vs Placebo, Chart Exploratory Endpoint HCMSQ-SoB Mean Change CAMZYOS® (mavacamten) vs Placebo, Chart

Mean baseline HCMSQ-SoB domain score (SD) was 5 (3) for both CAMZYOS (n=108) and placebo (n=109) groups.1The HCMSQ-SoB domain score measures the frequency and severity of shortness of breath. The HCMSQ-SoB scale score ranges from 0 to 18 with lower scores representing less shortness of breath.1 Missing data were not imputed to summarize the baseline and change from baseline to week 30 values. Difference in mean change from baseline between treatment groups was estimated using a mixed model for repeated measures.1 Patient-reported outcomes were analyzed with all available data. Sensitivity analyses were conducted to assess the effect of the missing data. When missing data were imputed with unfavorable results for the CAMZYOS group, the treatment effects of HCMSQ-SoB remained significant (P<0.05).2

  • HCMSQ-SoB=Hypertrophic Cardiomyopathy Symptom Questionnaire-Shortness of Breath subscore.

The HCMSQ-SoB is an assessment created expressly for the EXPLORER-HCM
study that measures the frequency and severity of shortness of breath.4

Select Important Safety Information

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%).
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.

Please see additional Important Safety Information below, including Boxed WARNING.

Read the EXPLORER-HCM reprint >
Exploratory endpoint:
cardiac biomarkers

For patients with NYHA class II–III
obstructive HCM,

Primary composite functional endpoint

To achieve the primary composite functional endpoint, patients needed to achieve either ≥1 NYHA class improvement and an increase of ≥1.5 mL/kg/min in peak oxygen consumption (pVO2) or no worsening NYHA class and an increase of ≥3.0 mL/kg/min in pVO2.1,2

At week 30, 37% (n=45/123) of patients taking CAMZYOS® achieved the primary composite functional endpoint vs 17% (n=22/128) with placebo (95% CI: 9, 30; P=0.0005).1,2

Exploratory Endpoint: Mean Change in NT-proBNP Over the 30-Week Treatment Period1,2

Changes in NT-proBNP Levels for Patients Receiving CAMZYOS and Placebo1,2

The reduction in NT-proBNP was 80% greater with CAMZYOS than for placebo. The clinical significance of these findings is unknown.1,2

Treatment difference (95% CI): 0.20 (0.17, 0.24)

While this endpoint was prespecified, it was not powered for significance.3

Exploratory Endpoint NT-proBNP Mean Change CAMZYOS® (mavacamten) vs Placebo, Chart Exploratory Endpoint NT-proBNP Mean Change CAMZYOS® (mavacamten) vs Placebo, Chart

NT-proBNP is a marker for negative cardiac outcomes in patients with obstructive hypertrophic cardiomyopathy.4

CI=confidence interval; NT-proBNP=N-terminal pro B-type natriuretic peptide.

The efficacy of CAMZYOS was evaluated in EXPLORER-HCM, a phase 3, double-blind, randomized, placebo-controlled trial that enrolled 251 adult patients with symptomatic (New York Heart Association [NYHA] class II and III) obstructive HCM, with left ventricular outflow tract (LVOT) peak gradient ≥50 mmHg, and left ventricle ejection fraction (LVEF) ≥55% at rest or with provocation.1 Patients were randomized in a 1:1 ratio to receive CAMZYOS (n=123) or placebo (n=128) once daily for 30 weeks.1

All subjects were initiated on CAMZYOS 5 mg (or matching placebo) once daily, and the dose was periodically adjusted to optimize patient response (decrease in LVOT gradient with Valsalva maneuver), maintain LVEF ≥50%, and was further informed by plasma concentrations of CAMZYOS.1,2

Select Important Safety Information

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%).
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.

Please see additional Important Safety Information below, including Boxed WARNING.

Read the EXPLORER-HCM reprint >
See the select safety profile

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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. [draft package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2023.
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References:

  1. CAMZYOS. [draft package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2023.
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