Aficamten for Hypertrophic Cardiomyopathy

(ACACIA-HCM Trial)

Recruiting at 134 trial locations

Overseen By Cytokinetics MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Cytokinetics

Must not be taking: Aficamten, Mavacamten

Disqualifiers: Valvular heart disease, Coronary artery stenosis, others

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: 72 weeks

500 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you have been treated with mavacamten within 3 months prior to screening, this must be discussed with the medical monitor.

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

Research shows that Aficamten, a cardiac myosin inhibitor, can safely reduce heart obstruction and improve heart failure symptoms in patients with obstructive hypertrophic cardiomyopathy. Studies have demonstrated significant improvements in heart function and symptoms within weeks of starting treatment, with effects lasting up to 48 weeks. ^{1 2 3 4 5}

Is aficamten safe for humans?

Aficamten has been shown to be safe and well-tolerated in healthy adults, with no serious side effects reported in a study involving both single and multiple doses. Mild side effects were noted, but there were no significant adverse effects on heart function. ^{1 2 3 5 6}

How is the drug Aficamten different from other treatments for hypertrophic cardiomyopathy?

Aficamten is unique because it is a cardiac myosin inhibitor that directly targets the heart muscle's contractility, helping to reduce the obstruction in the heart's outflow tract. Unlike traditional treatments like beta-blockers and calcium channel blockers, Aficamten has fewer drug interactions and a shorter half-life, making it potentially more effective and easier to manage. ^{1 2 3 6 7}

What is the purpose of this trial?

This trial is testing aficamten, a medication that may help people with a thickened heart muscle condition. It aims to improve their quality of life and ability to exercise. The drug works by making the heart muscle less stiff, which could help the heart pump blood better.

Research Team

Cytokinetics MD

Principal Investigator

Cytokinetics

Eligibility Criteria

Adults aged 18-85 with non-obstructive hypertrophic cardiomyopathy (nHCM), specifically those who are somewhat limited in physical activity but not bedridden. They must have a body mass index under 40, no recent heart surgeries or treatments with similar drugs, and be able to exercise on a treadmill or bicycle.

Inclusion Criteria

Your NT-proBNP levels meet certain requirements.

My heart condition mildly or moderately affects my daily activities.

You can join the study if you have not had a blockage in a body cavity.

Exclusion Criteria

I have a condition that causes thickening of the heart muscle, similar to nHCM.

My heart's pumping strength is below normal.

I have low oxygen levels without extra oxygen or severe lung/blood pressure issues.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive aficamten or placebo with dose levels guided by echocardiography assessments

72 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Aficamten
• Placebo

Trial Overview The trial is testing Aficamten against a placebo to see if it improves life quality, exercise ability, and health outcomes for people with nHCM. Participants will either receive the actual drug or a placebo without knowing which one they're getting.

Participant Groups

Group I: Aficamten Experimental Treatment 1 Intervention

Participants in this arm will receive a single daily oral dose of 5 mg, 10 mg, 15 mg, or 20 mg of aficamten with dose levels guided by echocardiography assessments, for up to 72 weeks.

Group II: Placebo Placebo Group 1 Intervention

Participants in this arm will receive placebo, for up to 72 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

Bayer

Industry Sponsor

Trials

2,291

Recruited

25,560,000+

Founded

1863

Headquarters

Leverkusen, Germany

Known For

Pharmaceutical Innovations

Top Products

Aspirin, Aleve, Yaz, Nexavar

Bill Anderson

Bayer

Chief Executive Officer since 2023

BSc in Chemical Engineering from the University of Texas, MSc in Chemical Engineering and Management from MIT

Michael Devoy

Bayer

Chief Medical Officer since 2014

MD, PhD

Findings from Research

Aficamten is a new cardiac myosin inhibitor that effectively lowers left ventricular outflow tract (LVOT) gradients and improves heart failure symptoms in patients with obstructive hypertrophic cardiomyopathy (HCM), showing significant results within 2 weeks and sustained effects for up to 48 weeks based on the REDWOOD-HCM study.

Compared to traditional treatments like beta-blockers and calcium channel blockers, aficamten directly targets the underlying disease mechanism by reducing hypercontractility and improving diastolic function, while also having a shorter half-life and fewer drug interactions, making it a safer and more convenient option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aficamten: A Breakthrough Therapy for Symptomatic Obstructive Hypertrophic Cardiomyopathy. Sebastian, SA., Padda, I., Lehr, EJ., et al.[2023]

A single oral dose of the myosin inhibitor aficamten (2 mg/kg) in five cats with hypertrophic cardiomyopathy (HCM) led to significant changes in cardiac function, including reduced left ventricular fractional shortening and improved left ventricular dimensions without major side effects.

The results suggest that while aficamten can effectively alter cardiac function in HCM, a lower dose may be more optimal, indicating the need for further studies to refine dosing strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of a single dose of Aficamten (CK-274) on cardiac contractility in a A31P MYBPC3 hypertrophic cardiomyopathy cat model. Sharpe, AN., Oldach, MS., Kaplan, JL., et al.[2023]

Aficamten was found to be safe and well-tolerated in a phase 1 study involving 28 healthy Chinese adults, with no serious adverse events reported and only mild treatment-emergent adverse events occurring in 50% of participants.

The pharmacokinetics of aficamten were dose-proportional and similar to those observed in Western populations, supporting its potential for further clinical trials in patients with obstructive hypertrophic cardiomyopathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple doses of aficamten in healthy Chinese participants: a randomized, double-blind, placebo-controlled, phase 1 study. Zhao, X., Liu, H., Tian, W., et al.[2023]

Aficamten significantly reduced left ventricular outflow tract (LVOT) gradients in patients with obstructive hypertrophic cardiomyopathy (oHCM), showing mean differences of -40 mm Hg and -43 mm Hg at rest, and -36 mm Hg and -53 mm Hg with Valsalva, compared to placebo.

The treatment was well-tolerated with no interruptions, and while there were modest reductions in ejection fraction, aficamten led to a 62% reduction in the cardiac biomarker N-terminal pro-B-type natriuretic peptide, indicating potential improvements in heart function and symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 Study of Aficamten in Patients With Obstructive Hypertrophic Cardiomyopathy. Maron, MS., Masri, A., Choudhury, L., et al.[2023]

The SEQUOIA-HCM trial, involving 282 participants, is evaluating the safety and efficacy of aficamten compared to placebo in patients with obstructive hypertrophic cardiomyopathy (oHCM) over a 24-week period, aiming to improve functional capacity and reduce symptoms.

Despite advancements in managing oHCM that have lowered hospitalization and mortality rates, patients still experience significant quality of life issues, highlighting the need for effective new therapies like aficamten.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise Capacity in Patients With Obstructive Hypertrophic Cardiomyopathy: SEQUOIA-HCM Baseline Characteristics and Study Design. Coats, CJ., Maron, MS., Abraham, TP., et al.[2023]

Aficamten (CK-274) is a novel cardiac myosin inhibitor designed to treat hypercontractility in genetic hypertrophic cardiomyopathies, showing a predicted human half-life suitable for once-daily dosing and achieving steady state within two weeks.

In a phase I clinical trial, aficamten confirmed its predicted pharmacokinetic properties, indicating a wide therapeutic window and minimal interaction with cytochrome P450 enzymes, which suggests a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discovery of Aficamten (CK-274), a Next-Generation Cardiac Myosin Inhibitor for the Treatment of Hypertrophic Cardiomyopathy. Chuang, C., Collibee, S., Ashcraft, L., et al.[2021]

Mavacamten has been approved by the FDA as a novel treatment for symptomatic obstructive hypertrophic cardiomyopathy (HCM), showing improved clinical outcomes by targeting cardiac contractility at the sarcomere level.

Aficamten, another cardiac myosin inhibitor currently in phase III clinical trials, represents a promising new therapy for HCM, indicating a shift in management strategies from traditional negative inotropic agents to more targeted treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aficamten-A Second in Class Cardiac Myosin Inhibitor for Hypertrophic Cardiomyopathy. Patel, J., Wang, A., Naidu, SS., et al.[2023]

References

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

Aficamten: A Breakthrough Therapy for Symptomatic Obstructive Hypertrophic Cardiomyopathy. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of a single dose of Aficamten (CK-274) on cardiac contractility in a A31P MYBPC3 hypertrophic cardiomyopathy cat model. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple doses of aficamten in healthy Chinese participants: a randomized, double-blind, placebo-controlled, phase 1 study. [2023]

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

Phase 2 Study of Aficamten in Patients With Obstructive Hypertrophic Cardiomyopathy. [2023]

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

Exercise Capacity in Patients With Obstructive Hypertrophic Cardiomyopathy: SEQUOIA-HCM Baseline Characteristics and Study Design. [2023]

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

Discovery of Aficamten (CK-274), a Next-Generation Cardiac Myosin Inhibitor for the Treatment of Hypertrophic Cardiomyopathy. [2021]

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

Aficamten-A Second in Class Cardiac Myosin Inhibitor for Hypertrophic Cardiomyopathy. [2023]