EDG-5506 for Becker Muscular Dystrophy

(ARCH Trial)

Overseen By Edgewise Therapeutics

Age: 18 - 65

Sex: Male

Trial Phase: Phase 1

Sponsor: Edgewise Therapeutics, Inc.

Must not be taking: CYP3A4 inhibitors, Corticosteroids

Disqualifiers: Suicidal ideation, Psychiatric condition, others

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

Compensation: Varies

Number of Visits: 12

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called EDG-5506, which aims to protect and improve muscle function in those with Becker muscular dystrophy (BMD). The main goal is to determine the drug's safety and behavior in the body. The trial seeks men aged 18 to 55 who can walk with or without assistance and have a BMD diagnosis. Those who participated in a previous related study might be suitable candidates. Participants must also meet specific health criteria, such as having a healthy heart and no recent substance abuse issues. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects on people.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you cannot take certain drugs like moderate or strong CYP3A4 inhibitors or inducers. If you're on oral corticosteroids, you must not have taken more than 5 mg per day for over 5 days in the past 6 months.

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

Research has shown that sevasemten (EDG-5506) is being tested for its safety and effects on muscle function in people with Becker muscular dystrophy (BMD). In studies with BMD patients, sevasemten has helped stabilize muscle function by protecting muscle fibers from damage during physical activity.

Previous studies have examined how well participants can handle sevasemten. Participants have generally tolerated the treatment well, and monitoring safety remains a key part of the study. As this is an early-phase trial, researchers are closely observing for safety and side effects. This phase typically involves a small number of participants to ensure the treatment's safety before progressing to larger studies.

While the treatment is still under investigation, no major safety concerns have been reported so far. Please note that sevasemten is not yet approved by the FDA, and its use is currently limited to clinical trials. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Becker Muscular Dystrophy, which primarily focus on managing symptoms and slowing disease progression, EDG-5506 offers a new approach by targeting muscle protection directly. Researchers are excited about EDG-5506 because it uses a novel mechanism to stabilize muscle fibers, potentially reducing muscle damage and improving muscle function. This innovative approach could offer improved outcomes and quality of life for patients, setting it apart from existing therapies that don't directly address muscle fiber protection.

What evidence suggests that EDG-5506 might be an effective treatment for Becker muscular dystrophy?

Studies have shown promising results for EDG-5506 in treating Becker muscular dystrophy (BMD). Early findings suggest that EDG-5506 protects muscles by reducing the use of fast muscle fibers during activity, preventing damage. Research has also found a significant decrease in substances indicating muscle injury in patients taking the drug. Patients experienced physical improvements, and their muscle function remained stable, showing no decline. These results suggest EDG-5506 could effectively improve muscle health and function in people with BMD. ^{1 2 6 7 8}

Who Is on the Research Team?

Sam Collins, MBBS, PhD

Principal Investigator

Edgewise Therapeutics, Inc.

Are You a Good Fit for This Trial?

This trial is for adult males aged 18-55 with Becker Muscular Dystrophy who can walk at least 100 meters. They must have completed a prior EDG-5506 study, weigh over 50 kg, and have a BMI of 20-34 kg/m2. Those on recent investigational drugs, with certain medical conditions or taking high doses of corticosteroids are excluded.

Inclusion Criteria

I can walk 100 meters by myself or with help.

Participants who have completed Study EDG-5506-001

Body mass index (BMI) between 20 and 34 kg/m2 inclusive

Exclusion Criteria

Medical history or other medical or psychiatric condition including recent or active suicidal ideation/behavior or laboratory result or abnormality that may increase the risk of study participation or, in the Investigator's judgment, make the participant inappropriate for the study. Includes venous access that would be too difficult to facilitate repeated blood sampling.

I am taking medication that strongly affects liver enzymes.

I have taken high-dose oral steroids for more than 5 days in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sevasemten to assess safety and pharmacokinetics

24 months

Monthly visits for the first 12 months, then every 3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• EDG-5506

Trial Overview

The ARCH study is testing EDG-5506 in adults with Becker muscular dystrophy to see if it's safe and how the body processes it. It aims to protect and improve muscle function in patients by administering this experimental drug in an open-label, single-center Phase 1b setting.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 1 Intervention

Drug: Sevasemten

Who Is Running the Clinical Trial?

Edgewise Therapeutics, Inc.

Lead Sponsor

Trials

13

Recruited

1,000+

Medpace, Inc.

Industry Sponsor

Trials

98

Recruited

30,400+

Dr. August J. Troendle

Medpace, Inc.

Chief Executive Officer since 1992

MD from the University of Maryland, School of Medicine; MBA from Boston University

Dr. Reinilde Heyrman

Medpace, Inc.

Chief Medical Officer since 2017

MD

Published Research Related to This Trial

In a phase 3 study involving 79 patients aged 7-16 with Duchenne muscular dystrophy, eteplirsen treatment for 96 weeks resulted in a significant increase in dystrophin production (7-fold) and exon skipping (18.7-fold), indicating its efficacy in addressing the underlying cause of the disease.

The study also demonstrated a favorable safety profile, with most adverse events being mild to moderate and unrelated to the treatment, while showing a notable slowing of disease progression compared to untreated controls.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-Label Evaluation of Eteplirsen in Patients with Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping: PROMOVI Trial. McDonald, CM., Shieh, PB., Abdel-Hamid, HZ., et al.[2022]

The bmx mouse model, created using CRISPR/Cas9 technology, successfully mimics Becker muscular dystrophy (BMD) by expressing a common mutation in the dystrophin gene, allowing for the study of muscle and heart dysfunction associated with the disease.

This model shows significant muscle weakness and heart dysfunction compared to wild-type mice, with increased muscle damage and inflammation, making it a valuable tool for understanding BMD and testing potential therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The X-linked Becker muscular dystrophy (bmx) mouse models Becker muscular dystrophy via deletion of murine dystrophin exons 45-47. Heier, CR., McCormack, NM., Tully, CB., et al.[2023]

Edasalonexent (CAT-1004) is a promising treatment for Duchenne muscular dystrophy (DMD) that works by inhibiting the NF-κB pathway, which is linked to inflammation and muscle degeneration, showing significant effects in reducing NF-κB activity in a study with 79 adult participants.

The treatment was found to be safe and well tolerated, with mild side effects like diarrhea and headache, indicating its potential for therapeutic use in DMD and other diseases related to NF-κB activation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Novel NF-κB Inhibitor, Edasalonexent (CAT-1004), in Development as a Disease-Modifying Treatment for Patients With Duchenne Muscular Dystrophy: Phase 1 Safety, Pharmacokinetics, and Pharmacodynamics in Adult Subjects. Donovan, JM., Zimmer, M., Offman, E., et al.[2018]

In a phase 3 study involving 131 children aged 4 to under 8 years with Duchenne muscular dystrophy, edasalonexent was generally well-tolerated and had a manageable safety profile, with most side effects being mild gastrointestinal issues like diarrhea.

While edasalonexent did not show statistically significant improvements in overall muscle function compared to placebo, younger patients (6 years or younger) demonstrated more promising results, suggesting that early treatment may help slow disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized, Double-Blind, Placebo-Controlled, Global Phase 3 Study of Edasalonexent in Pediatric Patients with Duchenne Muscular Dystrophy: Results of the PolarisDMD Trial. Finkel, RS., McDonald, CM., Lee Sweeney, H., et al.[2021]

Citations

1.

edgewisetx.com

edgewisetx.com/wp-content/uploads/2024/08/WMS_Symposium_Donovan_ARCH_6_mos_FINAL_SLIDES_for_pdf.pdf

EDG-5506

pharmacokinetics (PK) of EDG-5506 in adults with Becker muscular dystrophy. (BMD). —12 patients enrolled, ambulatory with BMD, including all from Phase 1 study.

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05291091

NCT05291091 | Phase 2 Study of EDG-5506 in Becker ...

The EDG-5506-201 CANYON study was expanded to include an additional 120 adult participants in a cohort called GRAND CANYON, that is a multicenter, randomized, ...

3.

institut-myologie.org

institut-myologie.org/en/2025/07/17/edg-5506-sevasemten-stabilises-functional-scores-in-beckers-myopathy/

EDG-5506 (sevasemten) stabilises functional scores in ...

EDG-5506 limits the recruitment of fast muscle fibres during muscular effort, protecting the muscle from possible mechanical damage.

4.

parentprojectmd.org

parentprojectmd.org/https-investors-edgewisetx-com-news-news-details-2022-edgewise-therapeutics-announces-positive-2-month-interim-results-from-the-arch-open-label-study-of-edg-5506-in-adults-with-becker-muscular-dystr/

Edgewise Announces Positive 2-Month Interim Results ...

Treatment with EDG-5506 led to a significant decrease in key biomarkers of muscle damage when assessed by laboratory assays. Importantly, ...

5.

neurologylive.com

neurologylive.com/view/therapeutic-potential-edg-5506-treating-becker-muscular-dystrophy-joanne-donovan

Therapeutic Potential of EDG-5506 in Treating Becker ...

The results so far have been highly encouraging, with reductions in muscle damage biomarkers and physical improvements seen in patients." Becker ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05160415?cond=Becker%20muscular%20dystrophy&rank=3

A Study of EDG-5506 in Adult Males With Becker Muscular ...

This open-label study evaluated the safety, tolerability, and pharmacokinetics (PK) of sevasemten in participants with BMD who completed the ...

7.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40452637/

A Phase 1, Double-Blind, Placebo-Controlled Trial of ...

Sevasemten (EDG-5506) is an orally administered, investigational small molecule that selectively modulates fast muscle fiber contraction by inhibiting fast ...

8.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0960896622004424

P.124 EDG-5506 targets fast skeletal myosin and reduces ...

To assess safety, pharmacokinetics (PK), pharmacodynamics and biomarkers of muscle damage in healthy adults and adults with BMD.