Mavacamten for Hypertrophic Cardiomyopathy

Recruiting at 101 trial locations

Overseen By BMS Study Connect Contact Center www.BMSStudyConnect.com

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Bristol-Myers Squibb

Disqualifiers: Phenocopy diseases, LVEF <50%, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 9 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 200 weeks

40 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the efficacy, safety, and pharmacokinetics of mavacamten in adolescent patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but it mentions that you should not have any planned increases in your HCM medication dose. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Mavacamten for treating hypertrophic cardiomyopathy?

Research shows that Mavacamten, a drug that helps the heart muscle work better, improves symptoms and exercise ability in people with hypertrophic cardiomyopathy. It also reduces the need for certain heart surgeries and is well-tolerated by patients. ^{1 2 3 4 5}

Is Mavacamten safe for humans?

Mavacamten, also known as Camzyos or MYK-461, has been studied in clinical trials for hypertrophic cardiomyopathy and was generally well tolerated, with some patients experiencing serious adverse events. It was approved by the FDA in April 2022, indicating that its benefits outweigh the risks for its intended use. ^{1 3 4 6 7}

How is the drug Mavacamten unique in treating hypertrophic cardiomyopathy?

Mavacamten is unique because it is a first-of-its-kind drug that directly targets the heart's muscle fibers to reduce excessive contraction, unlike other treatments that mainly focus on symptom relief. It works by inhibiting myosin, a protein involved in muscle contraction, which helps improve heart function in people with hypertrophic cardiomyopathy. ^{1 2 6 8 9}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

This trial is for adolescents with obstructive hypertrophic cardiomyopathy (HCM) who show symptoms. Specific details about eligibility criteria are not provided, but typically participants must meet certain health standards and may be required to have a specific level of disease severity.

Inclusion Criteria

I have been diagnosed with hypertrophic cardiomyopathy (HCM).

My heart has a blockage in the outflow tract.

I am experiencing symptoms.

Exclusion Criteria

Evidence of LVEF <50% in prior 6 months

My heart muscle thickening is not due to sarcomere dysfunction.

I am scheduled for a major heart procedure or an increase in my heart condition medication.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive mavacamten or placebo from day 1 to end of treatment at week 200

200 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• Mavacamten

Trial Overview The study tests the effectiveness and safety of a drug called Mavacamten compared to a placebo in young patients with HCM. It also looks at how the body processes the drug.

Participant Groups

Group I: Placebo Experimental Treatment 1 Intervention

Participants assigned to this arm will receive mavacamten (1 mg to 15 mg) from week 28 to end of treatment at week 200.

Group II: Mavacamten Experimental Treatment 1 Intervention

Participants assigned to this arm will receive mavacamten (1 mg to 15 mg) from day 1 to end of treatment at week 200.

Mavacamten is already approved in United States, European Union, Canada, Switzerland, Brazil for the following indications:

Approved in United States as Camzyos for:

• Symptomatic obstructive hypertrophic cardiomyopathy (oHCM)

Approved in European Union as Camzyos for:

• Symptomatic obstructive hypertrophic cardiomyopathy (oHCM)

Approved in Canada as Camzyos for:

• Symptomatic obstructive hypertrophic cardiomyopathy (oHCM)

Approved in Switzerland as Camzyos for:

• Symptomatic obstructive hypertrophic cardiomyopathy (oHCM)

Approved in Brazil as Camzyos for:

• Symptomatic obstructive hypertrophic cardiomyopathy (oHCM)

Who Is Running the Clinical Trial?

Bristol-Myers Squibb

Lead Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Findings from Research

Mavacamten (Camzyos) is a newly approved treatment for obstructive hypertrophic cardiomyopathy (HCM) that works by selectively inhibiting myosin, a key protein in the heart's muscle cells, to improve heart function directly at the sarcomere level.

This treatment addresses the underlying causes of HCM, unlike current options that mainly provide symptomatic relief, potentially leading to better outcomes for patients with this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mavacamten, a precision medicine for hypertrophic cardiomyopathy: From a motor protein to patients. Nag, S., Gollapudi, SK., Del Rio, CL., et al.[2023]

Mavacamten effectively reduces left ventricular outflow obstruction and improves heart function in patients with obstructive hypertrophic cardiomyopathy, offering a new treatment option for those who do not respond to standard therapies.

Despite its efficacy, mavacamten is not considered cost-effective, with a high acquisition cost leading to significant expenses for additional quality-adjusted life years, and its role in treating nonobstructive hypertrophic cardiomyopathy remains unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mavacamten, a First-in-Class Cardiac Myosin Inhibitor for Obstructive Hypertrophic Cardiomyopathy. Dalo, JD., Weisman, ND., White, CM.[2023]

Mavacamten is a targeted cardiac-specific myosin inhibitor approved for treating adults with symptomatic obstructive hypertrophic cardiomyopathy (oHCM), showing significant efficacy in reducing left ventricular outflow tract gradients and improving exercise capacity in Phase 2 and 3 clinical trials.

The treatment was well tolerated and led to favorable cardiac remodeling, reducing the need for invasive septal reduction therapy in patients with drug-refractory symptoms, indicating its potential as a key option in managing oHCM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mavacamten: a first-in-class myosin inhibitor for obstructive hypertrophic cardiomyopathy. Braunwald, E., Saberi, S., Abraham, TP., et al.[2023]

Mavacamten, a new cardiac myosin inhibitor, significantly improves exercise capacity and functional status in patients with hypertrophic cardiomyopathy (HCM), achieving higher rates of primary composite endpoints compared to placebo in three randomized controlled trials involving 422 participants over a mean follow-up of 24 weeks.

While mavacamten reduces the need for septal reduction therapy (SRT), it is associated with higher rates of treatment-emergent adverse events (TEAEs), indicating a need for further research on its long-term safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mavacamten Treatment for Hypertrophic Cardiomyopathy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Ismayl, M., Abbasi, MA., Marar, R., et al.[2022]

In a study of 251 patients with symptomatic obstructive hypertrophic cardiomyopathy, mavacamten significantly improved cardiac function, with 80.9% of patients showing complete resolution of mitral valve systolic anterior motion after 30 weeks, compared to only 34.0% in the placebo group.

Mavacamten also led to significant improvements in diastolic function, as evidenced by reductions in left atrial volume index and lateral E/e', which were associated with decreased levels of a biomarker indicating myocardial wall stress, highlighting its efficacy in addressing key pathophysiological aspects of the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Mavacamten on Echocardiographic Features in Symptomatic Patients With Obstructive Hypertrophic Cardiomyopathy. Hegde, SM., Lester, SJ., Solomon, SD., et al.[2022]

Mavacamten (Camzyos™) is an oral medication specifically designed to inhibit cardiac myosin, and it was approved in April 2022 for treating adults with symptomatic obstructive hypertrophic cardiomyopathy (HCM) classified as NYHA class II-III.

The approval of mavacamten marks a significant milestone in HCM treatment, as it aims to improve both functional capacity and symptoms in affected patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mavacamten: First Approval. Keam, SJ.[2022]

Mavacamten has been shown to be effective in improving clinical responses and reducing NYHA function class in patients with hypertrophic cardiomyopathy (HCM), based on a meta-analysis of 539 patients across four clinical trials.

The drug was well-tolerated with no significant increase in serious adverse events compared to placebo, indicating its safety for use in HCM patients, particularly those with hypertrophic obstructive cardiomyopathy (HOCM).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of mavacamten for treatment of hypertrophic cardiomyopathy: a systematic review and meta-analysis of randomized clinical trials. Rabiee Rad, M., Ghasempour Dabaghi, G., Habibi, D.[2023]

Mavacamten is a new treatment option for hypertrophic cardiomyopathy (HCM), a hereditary heart condition, expanding the limited pharmacological options currently available, which include beta blockers and calcium channel blockers.

Current evidence suggests that mavacamten is particularly effective for patients with symptomatic obstructive HCM, indicating its potential to significantly improve patient outcomes in this specific group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mavacamten, an Alternative to Septal Reduction Therapy for Patients with Hypertrophic Cardiomyopathy. Desai, MY., Hajj Ali, A.[2023]

Mavacamten has shown promising efficacy in treating symptomatic hypertrophic cardiomyopathy (HCM) in Phase 2 and 3 trials, leading to significant improvements in symptoms and physiological metrics, particularly in patients with obstructive HCM.

The treatment resulted in minimal adverse events, indicating a favorable safety profile, while effectively reducing the left ventricular outflow tract (LVOT) gradient and improving quality of life measures such as the Kansas City Cardiomyopathy Questionnaire (KCCQ) scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mavacamten: a novel small molecule modulator of β-cardiac myosin for treatment of hypertrophic cardiomyopathy. Tower-Rader, A., Ramchand, J., Nissen, SE., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Mavacamten, a precision medicine for hypertrophic cardiomyopathy: From a motor protein to patients. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Mavacamten, a First-in-Class Cardiac Myosin Inhibitor for Obstructive Hypertrophic Cardiomyopathy. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Mavacamten: a first-in-class myosin inhibitor for obstructive hypertrophic cardiomyopathy. [2023]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Mavacamten Treatment for Hypertrophic Cardiomyopathy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Effect of Mavacamten on Echocardiographic Features in Symptomatic Patients With Obstructive Hypertrophic Cardiomyopathy. [2022]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Mavacamten: First Approval. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Safety and efficacy of mavacamten for treatment of hypertrophic cardiomyopathy: a systematic review and meta-analysis of randomized clinical trials. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Mavacamten, an Alternative to Septal Reduction Therapy for Patients with Hypertrophic Cardiomyopathy. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Mavacamten: a novel small molecule modulator of β-cardiac myosin for treatment of hypertrophic cardiomyopathy. [2022]