GRAND CANYON: Clinical Study in Becker Muscular Dystrophy (Becker)
A Pivotal Study Investigating the Safety and Efficacy of Sevasemten (EDG-5506) in Ambulatory Adults with a Mutation in the Dystrophin Gene and a Phenotype in Becker.
ABOUT BECKER
A devastating neuromuscular disease causing progressive weakness and loss of function in skeletal and cardiac muscles.
ABOUT SEVASEMTEN (EDG-5506)
An investigational small molecule designed to selectively bind to fast skeletal muscle myosin to reduce contraction-induced muscle injury.
ABOUT GRAND CANYON
A pivotal randomized, double-blind placebo-controlled study in adults with Becker.
ABOUT BECKER MUSCULAR DYSTROPHY (BECKER)
Becker muscular dystrophy (also known as Becker) is an X-linked genetic, neuromuscular disorder that causes progressive weakness and loss of function of the skeletal and cardiac muscles, predominantly in males. Mutations in the dystrophin gene resulting in Becker lead to contraction-induced muscle damage, which is the primary driver of muscle loss and impaired motor function. Functional decline can begin at any age; once that loss begins, the decline is irreversible and continues throughout the rest of the patient’s life. Some individuals living with Becker experience heart failure from cardiomyopathy, which may result in the need for heart transplantation or early death. The North Star Ambulatory Assessment (NSAA) is a multi-item scale utilized to measure changes in function in Becker.
Human skeletal muscle consists of both fast (type IIa, IIx) and slow (type I) myofibers defined by isoforms of myosin, a protein integral for muscle contraction. In Becker, fast (type II) myofibers are particularly susceptible to contraction-induced damage, ultimately leading to the irreversible loss of muscle function. Affected individuals may develop severe disability and potentially, early death. Muscle damage can be assessed in patients with Becker by measuring biomarkers like creatine kinase (CK) and fast skeletal muscle troponin I (TNNI2) in the blood.
Preventing this contraction-induced damage of fast myofibers may prevent myofiber degeneration and preserve skeletal muscle function in Becker.
ABOUT SEVASEMTEN (EDG-5506)
Sevasemten (EDG-5506) is designed to selectively bind to fast muscle myosin to reduce contraction-induced injury caused by the absence or truncation of dystrophin. Sevasemten (EDG-5506) is being studied to see if it limits muscle breakdown and disease progression in Becker.
Sevasemten (EDG-5506) is an investigational therapy that has not been approved for use in Becker Muscular Dystrophy by any regulatory agency, as its safety and effectiveness have not been established for the treatment of this disease.
ARCH is an open label, single-center study evaluating the safety, tolerability, impact on muscle damage biomarkers, and pharmacokinetics (PK) of varying doses of sevasemten (EDG-5506) orally dosed daily over 24 months in 12 adults with Becker.
Positive results of top-line data from the study, recently released, showed that over the two years of sevasemten treatment, participants’ NSAA scores stabilized and continued to diverge relative to functional declines reported across multiple Becker natural history studies, in which two-year mean decreases of 2.4 NSAA points were reported3,4,5. In addition, significant decreases in key biomarkers of muscle damage including CK and TNNI2 were observed in participants treated with sevasemten, which are consistent with prior observations.
The same study demonstrated that sevasemten was well tolerated over the 24 months of treatment in all participants with no discontinuations or dose reductions due to adverse events.
Clinical Experience with Sevasemten (EDG-5506) in the ARCH Study
Edgewise Therapeutics Figure 1. NSAA Shows Stabilization and Trend Toward Improvement After 24 Months of Dosing with sevasemten (EDG-5506)
ABOUT GRAND CANYON
GRAND CANYON is a study investigating the safety and efficacy of sevasemten (EDG-5506) in ambulatory adults with a mutation in the dystrophin gene and a phenotype of Becker.
PRIMARY OBJECTIVE
To assess efficacy of treatment with sevasemten (EDG-5506) in adults with Becker
To assess the safety and tolerability of sevasemten (EDG-5506)
STUDY DESIGN
This study will use a double-blind, randomized, placebo-controlled design to investigate the safety and efficacy of sevasemten (EDG-5506) dosed for 18 months in participants with Becker.
Approximately 120 adult participants with Becker are planned to be enrolled.
KEY ELIGIBILITY CRITERIA
INCLUSION CRITERIA
Adults 18 to 50 years old (inclusive) at the time of screening visit, with a documented dystrophin mutation and phenotype consistent with Becker, and history of being ambulatory beyond 16 years of age without steroids or a history of being ambulatory beyond 18 years of age with steroids.
Male sex at birth.
Able to complete the 100-meter timed test in <200 seconds with or without use of mobility aid devices.
EXCLUSION CRITERIA
History of neoplastic disease (except for adequately treated non-melanomatous skin carcinoma).
Echocardiogram ejection fraction <40%.
Predicted forced vital capacity (FVC) <60% or using daytime (mechanical or noninvasive) ventilatory support.
Moderate or severe renal or hepatic impairment, eGFR <60 mL/min/1.73 m2).
Positive test for hepatitis C antibody (unless negative hepatitis C virus polymerase chain reaction), hepatitis B surface antigen, or human immunodeficiency virus antibody.
PRIOR/CONCOMITANT THERAPY
Receipt of oral corticosteroids for the treatment of Becker in the previous 6 months.
Receiving moderate or strong cytochrome P450 CYP3A4 inhibitors or inducers.
Receipt of an investigational drug within 30 days or 5 half-lives (whichever is longer) of the screening visit in the present study.
Please see clinicaltrials.gov NCT05291091 for more information about the study.
CONTACT US
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SOURCES
Data on file, Edgewise Therapeutics; 2024.
Edgewise Therapeutics, Inc. Phase 2 study of sevasemten (EDG-5506) in Becker Muscular Dystrophy (GRAND CANYON). ClinicalTrials.gov identifier: NCT05291091. Updated November 3, 2023. Accessed November 20, 2023. https://clinicaltrials.gov/study/NCT05291091.
Phan H, et al. Treatment of Adults with Becker Muscular Dystrophy (Becker) with Sevasemten (EDG-5506), an Investigational Fast Myosin Inhibitor, Results in Reduction of Biomarkers of Muscle Damage and Improvement in Functional Stabilization. Poster presented at the 8th International Myology Congress; April 22-25, 2024; Paris, FR.
Bello L, et al. Sci Rep. 2016;6:32439. doi:10.1038/srep32439.
Van de Velde NM, et al. Neurology. 2021;97(5):e513-22.
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