Mavacamten for Hypertrophic Cardiomyopathy

Recruiting at 159 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: MyoKardia, Inc.

Must not be taking: Disopyramide, Ranolazine

Disqualifiers: ECG abnormalities, Syncope, Cardiac arrest, others

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

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: Long-term

282 Participants Needed

Trial Summary

What is the purpose of this trial?

Approximately 30 sites that enrolled participants in the MAVERICK-HCM (MYK-461-006) study in the United States (US) will initiate this study. Approximately 90 sites that enrolled participants in the EXPLORER-HCM (MYK-461-005) study in the US, Europe, and Israel will initiate this study. Note: Approximately 30 centers overlap between MAVERICK and EXPLORER.

Will I have to stop taking my current medications?

The trial requires that you stop taking disopyramide or ranolazine at least 14 days before the screening. Other medications are not specifically mentioned, so it's best to discuss your current medications with the study 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, is effective for treating hypertrophic cardiomyopathy. It improves symptoms, exercise capacity, and heart function, and has been shown to be better than a placebo in clinical trials. ^{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. ^{2 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 by inhibiting myosin, a protein responsible for muscle contraction, to reduce excessive heart muscle contraction in hypertrophic cardiomyopathy. Unlike other treatments that focus on symptom relief, Mavacamten addresses the underlying cause of the condition. ^{1 2 6 8 9}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

This trial is for adults over 45 kg who completed the MAVERICK-HCM or EXPLORER-HCM studies, have a left ventricular ejection fraction (LVEF) of ≥50%, and can undergo accurate heart scans. Women must not be pregnant, breastfeeding, and use effective birth control if sexually active. Exclusions include certain ECG abnormalities, recent serious cardiac events or arrhythmias, current treatment with specific drugs like disopyramide or ranolazine, significant other diseases that could affect study results or compliance.

Inclusion Criteria

I weigh more than 45 kg.

Your blood and urine test results are within the normal range according to the lab's standards.

I am not pregnant or breastfeeding and will use effective birth control during and 90 days after the trial.

Exclusion Criteria

Is unable to comply with the study requirements, including the number of required visits to the clinical site.

I have developed a significant cancer since joining the initial study.

Has any acute or serious comorbid condition (eg. major infection or hematologic, renal, metabolic, gastrointestinal, or endocrine dysfunction) that, in the judgment of the Investigator, could lead to premature termination of study participation or interfere with the measurement or interpretation of the efficacy and safety assessments in the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive active treatment with Mavacamten, with dosing adjusted based on target trough concentration or clinical response

Long-term

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants continue to receive Mavacamten to assess long-term safety

Long-term

Treatment Details

Interventions

• Mavacamten

Trial Overview The study tests the long-term safety of Mavacamten in patients with Hypertrophic Cardiomyopathy who previously participated in related trials. It will take place across approximately 90 sites globally including some locations from previous studies to ensure continuity and reliability of data.

Participant Groups

Group I: Group 3 Experimental Treatment 1 Intervention

Active Treatment for participants dose titrated to clinical response

Group II: Group 2 Experimental Treatment 1 Intervention

Active Treatment for participants with higher target trough concentration

Group III: Group 1 Experimental Treatment 1 Intervention

Active Treatment for participants with base target trough concentration

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?

MyoKardia, Inc.

Lead Sponsor

Trials

13

Recruited

1,000+

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 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 (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 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 First-in-Class Cardiac Myosin Inhibitor for Obstructive Hypertrophic Cardiomyopathy. [2023]

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

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