Aficamten vs Metoprolol for Hypertrophic Cardiomyopathy

(MAPLE-HCM Trial)

No longer recruiting at 74 trial locations

Overseen By Cytokinetics MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Cytokinetics

Must not be taking: Disopyramide, Beta blockers

Disqualifiers: Hypertension, Atrial fibrillation, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness and safety of two treatments for hypertrophic cardiomyopathy, a condition where the heart muscle thickens, hindering blood flow. The trial compares aficamten, a new potential drug, with metoprolol, both of which may ease symptoms and improve heart function. Participants will receive either aficamten or metoprolol, along with a placebo, to determine which treatment is more effective. The trial seeks individuals currently experiencing symptoms of hypertrophic cardiomyopathy and diagnosed with left ventricular outflow tract obstruction, a blockage in the heart. As a Phase 3 trial, this study is the final step before FDA approval, offering participants the opportunity to contribute to the development of a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you have a medical need for beta blockers or calcium-channel blockers that you can't stop. If you've taken mavacamten, you must stop it for at least 8 weeks before joining.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that aficamten is generally well-tolerated. In studies, patients using aficamten for up to 48 weeks experienced significant symptom relief and maintained a good safety record. Another study found that the treatment improved exercise ability, which is encouraging.

Metoprolol succinate, a common medication for heart problems, has a well-established safety record and is well-tolerated by most patients.

Both treatments are under study to ensure safety and effectiveness for people with hypertrophic cardiomyopathy, a condition where the heart muscle becomes too thick. The testing of aficamten in a later research phase suggests existing confidence in its safety for human use. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about aficamten for hypertrophic cardiomyopathy because it offers a novel approach compared to traditional beta-blockers like metoprolol. Unlike standard treatments that primarily reduce heart rate and blood pressure, aficamten works by directly targeting the cardiac myosin, which helps to decrease excessive heart muscle contraction. This mechanism could lead to improved heart function and symptom relief, offering hope for better outcomes in patients with this condition.

What evidence suggests that this trial's treatments could be effective for hypertrophic cardiomyopathy?

This trial will compare Aficamten with Metoprolol for treating hypertrophic cardiomyopathy. Research shows that Aficamten can greatly improve exercise ability and relieve symptoms in people with obstructive hypertrophic cardiomyopathy (oHCM). In one study, patients taking Aficamten exercised better, both at their hardest and at easier levels. Another study found that Aficamten provided long-lasting relief from heart blockage and symptoms for up to 48 weeks. These results suggest that Aficamten could effectively manage oHCM symptoms. Meanwhile, Metoprolol, another treatment option in this trial, is a well-known medication often used to treat heart issues by lowering heart rate and blood pressure, which can also help with symptoms. Both treatments have potential, but recent studies highlight Aficamten's promising results for oHCM. ^{1 3 4 6 7}

Who Is on the Research Team?

Scientific Leadership

Principal Investigator

Cytokinetics

Are You a Good Fit for This Trial?

Adults aged 18-85 with symptomatic hypertrophic cardiomyopathy and obstruction in the heart's left ventricle can join. They should have a BMI under 35, be class II or III for heart symptoms, and meet specific heart imaging criteria. Exclusions include high blood pressure at rest, certain other heart conditions, intolerance to beta blockers, recent severe arrhythmias or fainting episodes.

Inclusion Criteria

You need to have a specific type of heart test that shows certain results.

My heart condition was confirmed by a heart scan or ultrasound.

My heart condition mildly or moderately affects my daily activities.

Exclusion Criteria

I am scheduled for a heart procedure that can't be postponed.

I have a history of irregular heartbeats.

I have taken disopyramide in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either aficamten or metoprolol succinate with dose levels guided by echocardiography assessments for up to 24 weeks

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Aficamten (CK-3773274)
• Metoprolol succinate

Trial Overview The trial is testing Aficamten against Metoprolol Succinate to see which is better for adults with obstructive hypertrophic cardiomyopathy. Participants will receive varying doses of either drug or matching placebos to compare effectiveness and safety.

How Is the Trial Designed?

Group I: Aficamten up to 20 mg plus placebo for metoprolol Experimental Treatment 2 Interventions

Patients will receive doses of 5 mg, 10 mg, 15 mg or 20 mg of aficamten (CK-3773274) plus placebo for metoprolol succinate with dose levels guided by echocardiography assessments for up to 24 weeks.

Group II: Metoprolol succinate up to 200 mg plus placebo for aficamten Active Control 2 Interventions

Patients will receive 50 mg, 100 mg, 150 mg or 200 mg of metoprolol succinate plus placebo for aficamten (CK-3773274) with dose levels guided by echocardiography and heart rate assessments for up to 24 weeks.

Who Is Running the Clinical Trial?

Cytokinetics

Lead Sponsor

Trials

44

Recruited

17,500+

Sanofi

Industry Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

Published Research Related to This Trial

In a study of 974 patients with heart failure and reduced left ventricular function, atenolol showed a lower unadjusted mortality rate (3.2%) compared to metoprolol tartrate (7.5%) and was comparable to carvedilol (4.2%).

After adjusting for patient characteristics, atenolol was associated with a significantly lower risk of death compared to metoprolol tartrate, suggesting it may be an effective treatment option for heart failure, warranting further randomized trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival among patients with left ventricular systolic dysfunction treated with atenolol. Kapoor, JR., Heidenreich, PA.[2016]

Carvedilol, unlike metoprolol, antagonizes multiple adrenoreceptors involved in heart failure and also reduces oxidative stress, suggesting it may offer superior benefits for patients with heart failure.

Despite the potential advantages of carvedilol, the actual use of beta-blockers like carvedilol and metoprolol in heart failure patients remains low, partly due to a lack of clinical trials directly comparing their efficacy at optimal doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Critical differences among beta-adrenoreceptor antagonists in myocardial failure: debating the MERIT of COMET. McBride, BF., White, CM.[2018]

In a meta-analysis of 30,943 patients treated with carvedilol and 69,925 patients treated with metoprolol, carvedilol was found to reduce all-cause mortality compared to metoprolol tartrate, suggesting a potential advantage for carvedilol in this specific comparison.

However, when comparing carvedilol to metoprolol succinate, there were no significant differences in all-cause mortality or hospitalizations, indicating that both medications may be equally effective for patients with heart failure with reduced ejection fraction (HFrEF).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-analysis of the effects of carvedilol versus metoprolol on all-cause mortality and hospitalizations in patients with heart failure. Briasoulis, A., Palla, M., Afonso, L.[2018]

Citations

1. ir.cytokinetics.com ir.cytokinetics.com/press-releases/press-release-details/2025/Cytokinetics-Presents-New-Data-Related-to-Aficamten-at-the-HFSA-Annual-Scientific-Meeting-2025/default.aspx

Cytokinetics Presents New Data Related to Aficamten at ... Additional Data from MAPLE-HCM Show Aficamten Significantly Improves Measures of Maximal and Submaximal Exercise Capacity and Recovery ...

2. academic.oup.com academic.oup.com/eurheartj/article/46/40/4076/8133640

Efficacy of aficamten in patients with obstructive hypertrophic ... Patients with oHCM and mild symptoms at baseline treated with aficamten over 24 weeks demonstrate significant improvement in clinical outcome measures and, ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40540987/

48-Week Results From FOREST-HCM Aficamten treatment over 48 weeks was well tolerated and associated with substantial and durable relief of obstruction and symptom burden.

4. sciencedirect.com sciencedirect.com/science/article/pii/S2666602225000382

Efficacy of aficamten in obstructive hypertrophic ... In this meta-analysis, data pertaining to the outcomes of 596 patients, with obstructive hypertrophic cardiomyopathy (oHCM) or non-obstructive hypertrophic ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05767346

Study Details | NCT05767346 | Phase 3 Trial to Evaluate ... The purpose of this study is to compare the efficacy and safety of aficamten (CK-3773274) compared with metoprolol succinate in adults with symptomatic ...

6. ahajournals.org ahajournals.org/doi/10.1161/JAHA.124.038758

Safety and Efficacy of Mavacamten and Aficamten in ... In this review, we evaluated the pharmacologic profile and clinical outcomes for mavacamten and aficamten, 2 cardiac myosin inhibitors investigated in ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1071916425004312

A 96-Week Analysis From FOREST-HCM Efficacy and safety of aficamten in symptomatic nonobstructive hypertrophic cardiomyopathy: results from the REDWOOD-HCM trial, cohort 4. J ...