BMS-986435 for Heart Failure

(AURORA-HFpEF Trial)

Recruiting at 173 trial locations

Overseen By BMS Clinical Trials Contact Center www.BMSClinicalTrials.com

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Bristol-Myers Squibb

Disqualifiers: Obstructive cardiomyopathy, Cardiac amyloidosis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8-12 weeks

208 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment, BMS-986435 (also known as MYK-224), to determine its safety and effectiveness for people with heart failure who have normal pumping ability but still experience symptoms. The goal is to assess the treatment's efficacy and the body's response. Participants will receive either the actual treatment or a placebo (a harmless pill with no active ingredients) for comparison. Ideal candidates are adults with stable heart failure symptoms whose hearts can still pump normally. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important medical advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the study team for more details.

Is there any evidence suggesting that BMS-986435/MYK-224 is likely to be safe for humans?

Research shows that BMS-986435, also known as MYK-224, is being tested for safety in people with heart failure with preserved ejection fraction (HFpEF). Earlier studies have examined how well people tolerate this treatment, and it appears to be generally well-tolerated. These studies have not reported any major safety issues.

This treatment is now in a Phase 2 trial. In clinical trials, reaching this phase usually indicates that the treatment has already passed initial safety tests in humans. While this is encouraging, more research is needed to fully understand all possible effects and risks. Those considering joining a trial should consult their doctor, who can provide more information based on the latest research and help determine the best course for their health. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for heart failure?

Unlike the standard treatments for heart failure, which often include medications like ACE inhibitors, beta-blockers, and diuretics that mainly address symptoms and prevent disease progression, BMS-986435 offers a fresh approach. Researchers are excited because BMS-986435 works by targeting specific pathways related to the heart's muscle function, potentially offering a more direct and effective intervention. This new mechanism of action sets it apart from existing therapies and holds promise for improved outcomes in managing heart failure.

What evidence suggests that BMS-986435 might be an effective treatment for heart failure?

Research has shown that BMS-986435, also known as MYK-224, might help treat heart failure with preserved ejection fraction (HFpEF). Early studies suggest that this drug aids the heart muscle in relaxing and functioning better, potentially improving symptoms for people with HFpEF, a type of heart failure where the heart pumps normally but doesn't fill with blood properly. Recent scientific data have consistently shown positive results, supporting the potential benefits of this treatment for heart conditions. In this trial, participants will receive either BMS-986435 or a placebo to further study its effectiveness for HFpEF. Although the effectiveness for HFpEF is still under investigation, these findings are promising. ^{1 3 6 7 8}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

This trial is for adults with stable, symptomatic heart failure but whose hearts can still pump normally (HFpEF). People with obstructive or genetic heart muscle issues, storage disorders like cardiac amyloidosis, or any serious condition that could affect the study or be risky can't join.

Inclusion Criteria

I have stable heart failure with preserved ejection fraction.

Exclusion Criteria

Participants must not have any other acute or serious condition that could interfere with assessments during the study or may pose a risk to the participant

I do not have a known heart condition involving thickened heart muscles.

I do not have a condition like cardiac amyloidosis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BMS-986435/MYK-224 or placebo to evaluate safety, tolerability, and exposure-response

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BMS-986435/MYK-224

Trial Overview The study tests BMS-986435/MYK-224's safety and how well it's tolerated in people with HFpEF. It also looks at how drug levels relate to its effects. Participants will either receive this new drug or a placebo for comparison.

How Is the Trial Designed?

Group I: BMS-986435 Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

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

Published Research Related to This Trial

In a study comparing 4 donor hearts and 12 failing hearts from patients with heart failure, it was found that the activities of JNKs and p38-MAPKs were significantly higher in the failing hearts, suggesting their involvement in heart disease pathology.

While the total amounts of certain MAPKs were similar between donor and failing hearts, the reduced levels of the 46-kDa JNK in failing hearts indicate a potential alteration in MAPK signaling that could contribute to heart failure mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activation of c-Jun N-terminal kinases and p38-mitogen-activated protein kinases in human heart failure secondary to ischaemic heart disease. Cook, SA., Sugden, PH., Clerk, A.[2009]

The pro-drug DMX-10001, designed to inhibit cardiomyocyte death in myocardial infarction, was tested in a study involving 36 swine, but it did not significantly reduce infarct size despite achieving drug concentrations that were effective in mouse models and human stem cell-derived cardiomyocytes.

Although DMX-10001 showed a 27% reduction in infarct size when measured in grams or as a percentage of left ventricular mass, it ultimately failed to demonstrate efficacy in the large-mammal model, highlighting the challenges of translating results from smaller models to larger ones.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical trial of a MAP4K4 inhibitor to reduce infarct size in the pig: does cardioprotection in human stem cell-derived myocytes predict success in large mammals? Te Lintel Hekkert, M., Newton, G., Chapman, K., et al.[2022]

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) were used to demonstrate that selective MAP4K4 inhibitors can protect heart muscle cells from death caused by the chemotherapy drug doxorubicin (DOX), enhancing cell viability and reducing apoptosis.

The MAP4K4 inhibitors did not affect the effectiveness of DOX on cancer cells, suggesting that targeting MAP4K4 could provide a safe therapeutic strategy to prevent heart damage during cancer treatment without compromising anti-cancer efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective protection of human cardiomyocytes from anthracycline cardiotoxicity by small molecule inhibitors of MAP4K4. Golforoush, PA., Narasimhan, P., Chaves-Guerrero, PP., et al.[2022]

Transgenic mice with a cardiac-specific active form of MEK5alpha showed a significant increase in BMK1 activation, which is linked to improved heart function after ischemic injury.

The study suggests that BMK1 plays a protective role in the heart during ischemia/reperfusion events, indicating its potential as a therapeutic target for cardiac injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activation of big MAP kinase 1 (BMK1/ERK5) inhibits cardiac injury after myocardial ischemia and reperfusion. Cameron, SJ., Itoh, S., Baines, CP., et al.[2009]

Beta II protein kinase C (βIIPKC) is found to accumulate on the mitochondrial outer membrane in failing hearts, where it phosphorylates mitofusin 1 (Mfn1), leading to mitochondrial dysfunction and cell death.

The peptide SAMβA, which disrupts the interaction between Mfn1 and βIIPKC, has been shown to restore mitochondrial function and improve heart contractility in rats with heart failure, indicating its potential as a treatment for heart failure in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A selective inhibitor of mitofusin 1-βIIPKC association improves heart failure outcome in rats. Ferreira, JCB., Campos, JC., Qvit, N., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06122779

NCT06122779 | Study to Evaluate Safety, Tolerability and ... The purpose of this study is to evaluate the safety, tolerability, and exposure-response (E-R) of BMS-986435/MYK-224 in participants with symptomatic Heart ...

2. news.bms.com news.bms.com/news/corporate-financial/2025/Bristol-Myers-Squibb-Showcases-New-Long-Term-and-Real-World-Data-From-Cardiovascular-Portfolio-at-the-American-Heart-Association-Scientific-Sessions-2025/default.aspx

Corporate news details “The new data we are presenting at the American Heart Association's Scientific Sessions 2025 highlight the consistent and sustained results we've seen in our ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12383798/

Cardiac Myosin Inhibitors in the Treatment of Hypertrophic ... Hypertrophic cardiomyopathy (HCM) is a prevalent and often underdiagnosed genetic cardiac disorder characterized by left ventricular hypertrophy ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05556343

NCT05556343 | A Study to Evaluate the Efficacy, Safety ... The purpose of this study is to characterize the safety, tolerability, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of MYK-224 in participants ...

5. clinicaltrials.eu clinicaltrials.eu/inn/bms-986435/

BMS-986435: A Promising New Drug in Clinical Trials These trials aim to evaluate its safety, effectiveness, and potential benefits for patients with heart conditions, particularly those with Heart Failure with ...

6. bmsstudyconnect.com bmsstudyconnect.com/mx/en/clinical-trials/NCT06122779.html

study connect - BMS Clinical Trials Study to evaluate safety, tolerability and drug levels of BMS-986435/MYK-224 in participants with heart failure with preserved ejection fraction (HFpEF).

7. bmsclinicaltrials.com bmsclinicaltrials.com/us/en/clinical-trials/NCT05556343

Trial ID CV029-009 | NCT05556343 - BMS Clinical Trials A Study to Evaluate the Efficacy, Safety, and Tolerability of MYK-224 in Participants With Symptomatic Obstructive Hypertrophic Cardiomyopathy. Warning icon.

8. sigma.larvol.com sigma.larvol.com/product.php?e1=826692&tab=newstrac

MYK-224 News While mavacamten has established efficacy, next-generation agents like aficamten may offer improved safety and versatility. Further long-term studies are needed ...