Long-term Safety of Aficamten for Hypertrophic Cardiomyopathy

(FOREST-HCM Trial)

Enrolling by invitation at 106 trial locations

Overseen By Cytokinetics, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Cytokinetics

Must not be taking: Mavacamten

Disqualifiers: Atrial fibrillation, Septal reduction, 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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 5 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the long-term safety of aficamten (CK-3773274) for individuals with hypertrophic cardiomyopathy, a condition where the heart muscle thickens abnormally. The goal is to assess how well participants tolerate this medication over time. Participants will take a daily dose of aficamten, starting low and increasing to the highest dose they can handle. The trial seeks individuals who have completed a previous study with aficamten and have a heart measurement called LVEF at 55% or higher, indicating good heart function. As a Phase 2, Phase 3 trial, this research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, allowing participants to contribute to significant advancements in treatment.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot have taken mavacamten within 56 days before starting the trial. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that aficamten appears safe for people with hypertrophic cardiomyopathy, a condition where the heart muscle thickens excessively. In a 48-week study, patients taking aficamten tolerated it well and experienced significant relief from heart blockage and symptoms without major safety issues. Other findings support these results, showing a consistent safety record over time. This indicates that aficamten has not caused unexpected or severe side effects in past studies. While researchers continue to study the long-term safety of aficamten, these early results are promising for those considering joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for hypertrophic cardiomyopathy?

Unlike the standard treatments for hypertrophic cardiomyopathy, which typically include beta-blockers, calcium channel blockers, and disopyramide, aficamten offers a unique approach by targeting cardiac myosin. This new mechanism of action allows aficamten to directly modulate the heart muscle's contraction, potentially providing more precise control over the heart's function. Researchers are excited about aficamten because it could offer improved management of symptoms with a tailored dosing strategy, potentially leading to better outcomes for patients with this condition.

What evidence suggests that aficamten might be an effective treatment for hypertrophic cardiomyopathy?

Research has shown that aficamten is promising for treating hypertrophic cardiomyopathy, particularly the obstructive type (oHCM). Patients who took aficamten for 24 weeks showed noticeable improvements in symptoms and exercise capacity. A 48-week study found that aficamten provided lasting relief from heart blockage and reduced symptoms. This treatment reduces the heart's workload by slowing the contraction of the heart muscle. Overall, evidence suggests that aficamten could improve life for those with hypertrophic cardiomyopathy. ^{1 5 6 7 8}

Who Is on the Research Team?

Cytokinetics, MD

Principal Investigator

Cytokinetics

Are You a Good Fit for This Trial?

This trial is for individuals who have completed a previous Cytokinetics study with CK-3773274 and have a left ventricular ejection fraction (LVEF) of 55% or higher. It's not open to those who've had certain heart treatments, recent atrial fibrillation, or an investigational drug/device within the last month.

Inclusion Criteria

You have already taken part in a Cytokinetics study involving CK-3773274.

Your heart function is good, with a measurement of at least 55% at the screening visit.

Exclusion Criteria

I received a necessary shock from my defibrillator within the last 30 days.

I've had heart surgery or a procedure to reduce heart muscle thickness after my last CK-3773274 trial.

I recently developed a type of irregular heartbeat and started treatment for it less than 30 days ago.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a daily dose of aficamten, titrated to their maximum tolerated dose

Up to 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Open-label extension

Participants continue to receive aficamten to collect long-term safety and tolerability data

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• CK-3773274

Trial Overview The trial is focused on gathering long-term safety data for Aficamten (CK-3773274), which will be administered in doses ranging from 5 to 20 mg. This is an open-label study where all participants receive the drug.

How Is the Trial Designed?

Group I: Aficamten up to 20 mg Experimental Treatment 1 Intervention

Patients in this arm take daily dose of aficamten. Each patient will start at the lowest prespecified dose and titrate up to their maximum tolerated dose.

Who Is Running the Clinical Trial?

Cytokinetics

Lead Sponsor

Trials

44

Recruited

17,500+

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

Citations

1. 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, ...

2. 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 ...

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. nejm.org nejm.org/doi/full/10.1056/NEJMoa2401424

Aficamten for Symptomatic Obstructive Hypertrophic ... Aficamten is an oral selective cardiac myosin inhibitor that reduces left ventricular outflow tract gradients by mitigating cardiac hypercontractility.

5. 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 ...

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

Safety and Efficacy of Mavacamten and Aficamten in ... Cumulative long‐term efficacy and safety of mavacamten treatment in nonobstructive hypertrophic cardiomyopathy: updated interim analysis ...

7. ir.cytokinetics.com ir.cytokinetics.com/press-releases/press-release-details/2025/Cytokinetics-Presents-New-Data-Related-to-Aficamten-at-the-European-Society-of-Cardiology-Congress-2025/default.aspx

Cytokinetics Presents New Data Related to Aficamten at ... Longer-Term Data Presented Consistent with Previously Reported Safety Profile of Aficamten ... cardiac death in hypertrophic cardiomyopathy ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04848506

NCT04848506 | Open-label Extension Study to Evaluate ... Open-label Extension Study to Evaluate the Long-term Safety and Tolerability of Aficamten in Adults With HCM (FOREST-HCM). ClinicalTrials.gov ID NCT04848506.