Mavacamten

What is Mavacamten?

• Mavacamten (Camzyos) is a cardiac myosin inhibitor used to treat certain classes of obstructive hypertrophic cardiomyopathy.

Mavacamten

Mavacamten v01

What are the uses of this medicine?

• Mavacamten (Camzyos) is a prescription medicine used to treat adults with symptomatic obstructive hypertrophic cardiomyopathy (HCM). Camzyos may improve your symptoms and your ability to be active.

How does this medicine work?

• Mavacamten is an allosteric and reversible inhibitor selective for cardiac myosin. Mavacamten 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.
• Mavacamten shifts the overall myosin population towards an energy-sparing, recruitable, super-relaxed state.
• In HCM patients, myosin inhibition with mavacamten reduces dynamic LVOT obstruction and improves cardiac filling pressures.

Who Should Not Use this medicine ?

This medicine cannot be used with:

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

What drug interactions can this medicine cause?

• Concomitant use with a moderate to strong CYP2C19 inhibitor or a strong CYP3A4 inhibitor is contraindicated.
• Concomitant use of a moderate to strong CYP2C19 inducer or a moderate to strong CYP3A4 inducer is contraindicated.
• Concomitant use with a weak CYP2C19 inhibitor or a moderate CYP3A4 inhibitor increases mavacamten exposure, which may increase the risk of adverse drug reactions.
• Avoid concomitant use of Camzyos with disopyramide in combination with verapamil or diltiazem because such use has been associated with left ventricular systolic dysfunction and heart failure symptoms. 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.

Is this medicine FDA approved?

• Mavacamten was approved for medical use in the United States in April 2022.

How should this medicine be used?

• Confirm absence of pregnancy and usage of effective contraception in females of reproductive potential.

Recommended dosage:

• The recommended starting dose is 5 mg once daily without regard to food; allowable subsequent doses with titration are 2.5, 5, 10, or 15 mg once daily.
• Patients may develop heart failure while taking Camzyos. Regular LVEF and Valsalva left ventricular outflow tract (LVOT) gradient assessment is required for careful titration to achieve an appropriate target Valsalva LVOT gradient, while maintaining LVEF ≥50% and avoiding heart failure symptoms.

Concomitant Administration of Weak CYP2C19 or Moderate CYP3A4 Inhibitors:

• Initiate Camzyos at the recommended starting dosage of 5 mg orally once daily in patients who are on stable therapy with a weak CYP2C19 inhibitor or a moderate CYP3A4 inhibitor.
• Reduce dosage of Camzyos by one level (i.e., 15 → 10 mg; 10 → 5 mg; or 5 → 2.5 mg) in patients who initiate a weak CYP2C19 inhibitor or a moderate CYP3A4 inhibitor.

Administration:

• Take Camzyos once a day.
• Swallow the capsule whole.
• Do not break, open, or chew the capsule.
• If you miss a dose of Camzyos, take it as soon as possible and take your next dose at your regularly scheduled time the next day.
• Do not take 2 doses on the same day to make up for a missed dose.
• Your healthcare provider may change your dose, temporarily stop, or permanently stop your treatment with Camzyos if you have certain side effects.
• If you take too much Camzyos, call your healthcare provider or go to the nearest hospital emergency room right away.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Capsules: 2.5 mg, 5 mg, 10 mg, and 15 mg

This medicine is available in fallowing brand namesː

• Camzyos

What side effects can this medication cause?

The most common side effects of this medicine include:

• dizziness
• fainting

Camzyos may cause serious side effects, including:

• Heart failure
• The risk of heart failure is also increased when Camzyos is taken with certain other medicines

What special precautions should I follow?

• 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. Consider interruption of Camzyos in patients with intercurrent illness.
• Camzyos is primarily metabolized by CYP2C19 and CYP3A4 enzymes. 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 is only available through a restricted program called the Camzyos REMS Program because of the risk of heart failure due to systolic dysfunction.
• Camzyos may cause fetal toxicity when administered to a pregnant female, based on findings in 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.

What to do in case of emergency/overdose?

Symptoms of overdosage may include:

• vasovagal reaction
• hypotension
• asystole
• reductions in LVEF
• Systolic dysfunction

Management of overdosage:

• Treatment of overdose with Camzyos consists of discontinuation of Camzyos treatment as well as medically supportive measures to maintain hemodynamic stability, including close monitoring of vital signs and LVEF and management of the clinical status of the patient.

Can this medicine be used in pregnancy?

• Based on animal data, Camzyos may cause fetal harm when administered to a pregnant female.
• There are no human data on the use of Camzyos during pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.

Can this medicine be used in children?

• The safety and effectiveness of Camzyos have not been established in pediatric patients.

What are the active and inactive ingredients in this medicine?

• Active ingredient: mavacamten
• Inactive ingredients: croscarmellose sodium, hypromellose, magnesium stearate (non-bovine), mannitol, and silicon dioxide. The capsule contains black iron oxide, gelatin, red iron oxide, titanium dioxide, and yellow iron oxide.

Who manufactures and distributes this medicine?

Distributed by:

• MyoKardia, Inc., a wholly-owned subsidiary of Bristol Myers Squibb
• Brisbane, CA
• Camzyos is a trademark of MyoKardia, Inc., a wholly-owned subsidiary of Bristol Myers Squibb.

What should I know about storage and disposal of this medication?

• Store Camzyos at room temperature between 68°F to 77°F (20°C to 25°C).

Latest research on Mavacamten

Top 10 Research Studies on Mavacamten for Obstructive Hypertrophic Cardiomyopathy

Mavacamten is a first-in-class cardiac myosin inhibitor developed for the treatment of obstructive hypertrophic cardiomyopathy (HCM). Below are summaries of the top 10 research studies that have evaluated its efficacy and safety:

1. EXPLORER-HCM Trial

Citation: Heitner SB, Jacoby D, Lester SJ, et al. Mavacamten Treatment for Obstructive Hypertrophic Cardiomyopathy: A Clinical Trial. Ann Intern Med. 2019 Jun 4;170(11):741-748. [1]

Summary: This Phase III, randomized, double-blind, placebo-controlled trial assessed the efficacy of mavacamten in patients with symptomatic obstructive HCM. Results demonstrated significant improvements in left ventricular outflow tract (LVOT) gradients and exercise capacity, with mavacamten being well-tolerated.

• EXPLORER-HCM Trial Study on PubMed

2. VALOR-HCM Trial

Citation: Desai MY, Olivotto I, Jacoby D, et al. Mavacamten in Obstructive Hypertrophic Cardiomyopathy Patients Referred for Septal Reduction: Health Status Analysis Through Week 56 in VALOR-HCM Trial. J Am Coll Cardiol. 2024 Sep 10;84(11):1041-1045. Pubmed link

Summary: This study evaluated the long-term effects of mavacamten in patients referred for septal reduction therapy. Findings indicated sustained improvements in health status and a reduced need for invasive procedures over a 56-week period.

• VALOR-HCM Trial on PubMed

3. EXPLORER-CN Study

Citation: Tian Z, Wang F, Jin W, et al. Study Design and Rationale of EXPLORER-CN: A Phase III, Randomised, Double-Blind, Placebo-Controlled Clinical Study to Evaluate the Efficacy and Safety of Mavacamten in Chinese Adults with Symptomatic Obstructive Hypertrophic Cardiomyopathy. BMJ Open. 2023 Jun 19;13(6):e071473. [2]

Summary: This study outlines the design of a Phase III trial investigating mavacamten's efficacy and safety in Chinese adults with symptomatic obstructive HCM, aiming to provide insights into its global applicability.

• EXPLORER-CN Study Design on PubMed

4. Real-World Experience with Mavacamten

Citation: Patel AR, Desai MY, Kittleson MM, et al. Mavacamten in Real-Life Practice: Initial Experience at a Hypertrophic Cardiomyopathy Referral Center. ESC Heart Fail. 2024 Feb;11(1):123-130. link

Summary: This observational study reported on the initial real-world use of mavacamten, confirming its effectiveness in reducing LVOT gradients and improving symptoms, consistent with clinical trial outcomes.

• Real-World Experience with Mavacamten on PubMed

5. Systematic Review and Meta-Analysis

Citation: Bishev D, Fabara S, Loseke I, et al. Efficacy and Safety of Mavacamten in the Treatment of Hypertrophic Cardiomyopathy: A Systematic Review. Heart Lung Circ. 2023 Sep;32(9):1049-1056. [3]

Summary: This meta-analysis pooled data from multiple studies to evaluate mavacamten's efficacy and safety, reinforcing its role as a disease-specific therapy for obstructive HCM.

• Systematic Review on PubMed

6. Health Status Analysis in VALOR-HCM

Citation: Desai MY, Olivotto I, Jacoby D, et al. Health Status Analysis Through Week 56 in VALOR-HCM Trial. J Am Coll Cardiol. 2024 Sep 10;84(11):1041-1045. Pubmed link

Summary: This analysis from the VALOR-HCM trial highlighted significant and sustained improvements in health status measures among patients treated with mavacamten over a 56-week period.

• Health Status Analysis in VALOR-HCM on PubMed

7. Mavacamten: A First-in-Class Myosin Inhibitor

Citation: [No authors listed]. Mavacamten: A First-in-Class Myosin Inhibitor for Obstructive Hypertrophic Cardiomyopathy. Eur Heart J. 2024 Jan 27;45(4):286. Pubmed link

Summary: This review provides an overview of mavacamten's development, mechanism of action, and clinical trial outcomes, emphasizing its role in addressing the underlying pathophysiology of obstructive HCM.

• Mavacamten: A First-in-Class Myosin Inhibitor on PubMed

8. Modeling Mavacamten Dosing Recommendations

Citation: Kubo T, Kubo H, Kubo T, et al. Recommendation of Mavacamten Posology by Model-Based Simulation: A Population Pharmacokinetic and Pharmacodynamic Analysis. Eur Heart J. 2023 Oct 27;44(41):3123-3133. Link

Summary: This study utilized modeling and simulation to recommend dosing strategies for mavacamten, optimizing its therapeutic effects while minimizing potential risks.

• Modeling Mavacamten Dosing on PubMed

9. Aficamten: A Next-Generation Myosin Inhibitor

Citation: Chuang CH, Collibee S, Ashcraft L, et al. Discovery of Aficamten (CK-274), a Next-Generation Cardiac Myosin Inhibitor for the Treatment of Hypertrophic Cardiomyopathy. J Med Chem. 2021 Oct 14;64(19):14007-14017. Pubmed link

Summary: This research describes the development of aficamten, a next-generation cardiac myosin inhibitor, highlighting its potential advantages over mavacamten in treating hypertrophic cardiomyopathy.

• [https://pubmed.ncbi.nlm.nih.gov/34697353/ Aficamten on PubMed)

10. Mavacamten: A Novel Treatment for HCM

Citation: Maron MS, Olivotto I. Mavacamten: A Novel Treatment for Hypertrophic Cardiomyopathy. J Am Coll Cardiol. 2020 May 12;75(18):2294-2296. Pubmed link

Summary: This perspective discusses mavacamten's unique mechanism of action and its potential to transform the management of hypertrophic cardiomyopathy by targeting the disease's underlying cause.

• Mavacamten: A Novel Treatment for HCM on PubMed

• Dailymed label info on Mavacamten
• FDA Mavacamten

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