Breakthrough Clinical Results
Edgewise Therapeutics reported positive results from its sevasemten program for Becker and Duchenne muscular dystrophies. In Becker MD, open-label data from the MESA trial showed sustained disease stabilization for up to three years. A Type C meeting with the FDA provided a clear path to registration for Becker MD. Encouraging Phase 2 data from Duchenne MD trials (LYNX and FOX) identified a potential beneficial dose (10mg) for Phase 3. Edgewise plans to meet with the FDA in Q4 2025 to discuss a Phase 3 design for Duchenne MD and initiate the pivotal study in 2026.
Key Highlights
- Sustained disease stabilization in Becker MD patients for up to three years in the MESA open-label extension trial.
- Successful Type C meeting with the FDA providing a clear path to sevasemten registration for Becker MD.
- Encouraging Phase 2 data in Duchenne MD identifying a potential beneficial dose for Phase 3.
- Plans to meet with the FDA in Q4 2025 to discuss Phase 3 design for Duchenne MD and initiate the study in 2026.
Incidence and Prevalence
Global Epidemiology of Becker Muscular Dystrophy
Prevalence Rates
Becker muscular dystrophy (BMD) prevalence varies significantly across different regions:
- In the Northern Health Region of England, prevalence is 2.38/100,000 population
- North-West Tuscany, Italy showed an increase from 1.06 × 10⁻⁵ to 2.42 × 10⁻⁵ inhabitants after implementing molecular diagnostic methods
- A larger Italian population study reported a prevalence rate of 13.1 × 10⁻⁶
- Puerto Rico has an estimated prevalence of 2.84 per 100,000 males, which is noted to be higher than reported worldwide
Most neuromuscular disorders (NMDs) including BMD show prevalence rates between 1 and 10 per 100,000 population. Compared to 1991, prevalence rates of BMD have shown an increase, yet with highly overlapping ranges according to a world survey of neuromuscular disorders.
Incidence Rates
The available data on BMD incidence includes:
- In the Italian population study, the incidence rate was 5.5 × 10⁻⁵ live-born males
- The cumulative birth incidence in the Northern Health Region of England was at least 1 in 18,450 male live births, approximately one-third that of Duchenne muscular dystrophy
Genetic Profile and Mutation Rates
- The mutation rate for BMD was estimated at about 6.0 × 10⁻⁶ in the Italian population study
- Deletion is the most common form of mutation (66.7%) in the dystrophin gene
- Exons in segment 45 to 47 are the most frequently affected according to the Puerto Rico study
- A Hong Kong Chinese patient study found that the percentage of DMD exon deletions was significantly lower than the commonly quoted 60%, indicating an ethnic or regional difference
Regional Distribution and Demographics
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In Japan (Remudy registry study from July 2009 through September 2015):
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192 participants with dystrophinopathy had registered
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138 (71.9%) had BMD and 54 (28.1%) had intermediate muscular dystrophy
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Mean participant age was 34.80±13.3 years (range: 17-78)
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52.1% of participants were ambulant
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50.5% had cardiomyopathy and 35.9% had respiratory failure
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In the United States, 7% (20/299) of individuals with dystrophinopathy were classified as childhood-onset Becker muscular dystrophy
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In Lebanon, Duchenne and Becker muscular dystrophy combined were the second most frequently diagnosed NMDs (17% of patients)
Disease Progression and Clinical Heterogeneity
A 3-year longitudinal study of 83 BMD patients (aged 5-75 years at baseline) showed variable progression of outcomes resulting in significant heterogeneity of the clinical phenotype. Disease progression in BMD is largely manifest in adulthood, with relative stability or improved median function through childhood and adolescence.
Overall Prevalence of Neuromuscular Disorders
A conservative estimate of the overall prevalence of disabling inherited neuromuscular diseases (including BMD) among both sexes is around 286 × 10⁻⁶, or 1 in 3500 of the population. If severe disorders and rare forms are included, the overall prevalence could exceed 1 in 3000.
Study Design Parameters
Study Design Parameters and Endpoints in Key Becker Muscular Dystrophy Trials
Study Design Parameters
Several key studies have been conducted to investigate Becker muscular dystrophy (BMD):
- A 3-year, longitudinal, prospective study followed 83 patients with confirmed Becker muscular dystrophy (5-75 years at baseline) with annual assessments
- Age-stratified statistical analysis and modeling were conducted to analyze cross-sectional data, time-to-event data, and longitudinal data
- A qualitative study based on interviews with clinical investigators and parents of sons with Duchenne and Becker muscular dystrophy who participated in the phase IIa or IIb ataluren clinical trial in the United States
- A prospective study involving ten healthy volunteers and 30 patients suffering from Becker muscular dystrophy to evaluate the repeatability, precision and sensitivity of T1-mapping
- Implementation of a T1-mapping sequence dedicated to skeletal muscle imaging with 10s scan time per slice
Key Endpoints and Assessments
The studies utilized various endpoints to assess disease progression and treatment effects:
Primary Endpoints
- Muscle and pulmonary function outcomes were primary measurements in the longitudinal study
Secondary and Exploratory Endpoints
- Intramuscular fat fraction (FF) measured using a standard three-point Dixon method
- T1 values in muscles evaluated as a potential biomarker for monitoring fatty infiltrations
- North Star Ambulatory Assessment (showed a ceiling effect in cross-sectional binning analysis)
- Percentage predicted forced vital capacity (showed a decline over the life span)
- Motor functional outcomes (showed relative stability or improved median function through childhood and adolescence and decreasing function with age thereafter)
Patient Experience Measures
- Parental expectations and motivations for clinical trials
- Secondary benefits including hopefulness and powerful feelings associated with active efforts to affect the disease course
- Strong relationships between parents and clinical investigators reported as mutually important
Genetic Characteristics and Disease Progression
- Deletion mutations of dystrophin exons 45-47 or 45-48 were most common in BMD patients
- Variable progression of outcomes resulted in significant heterogeneity of the clinical phenotype
- Disease progression is largely manifest in adulthood
Emerging Approaches
- Human induced pluripotent stem cell (iPSC) technologies emerging as useful models for mechanistic studies, drug discovery, and cell-based therapy
- Genome editing technologies enabled correction of genetic mutations in cells in culture
Challenges in Clinical Trials
- Trial termination led to loss of engagement, distress, and feeling unprepared for participants
- High trial expectations were reported by parents and many clinicians
The studies demonstrate the complexity of BMD progression and highlight the importance of comprehensive assessment approaches that capture both objective measures of muscle function and patient/caregiver experiences. The variability in disease progression and genetic characteristics presents challenges for clinical trial design, emphasizing the need for age-stratified analyses and long-term follow-up to accurately assess treatment effects.
Drug used in other indications
Sevasemten Clinical Trials Beyond Becker Muscular Dystrophy
Based on the provided information, there is no evidence that sevasemten (EDG-5506) is currently undergoing clinical trials for any clinical indications beyond Becker muscular dystrophy (BMD).
The available information only describes sevasemten as "an orally administered, investigational small molecule that selectively modulates fast muscle fiber contraction by inhibiting fast myosin ATPase."
The only clinical trial mentioned in the information (NCT04585464) was a phase 1 study that assessed "the safety, tolerability, and pharmacokinetics (PK)/pharmacodynamics (PD) of sevasemten in healthy adult volunteers (HVs) and adults with Becker muscular dystrophy (BMD)."
No other disease indications or ongoing trials for other conditions are mentioned in relation to sevasemten. Similarly, there is no information available about intervention models for trials in indications other than Becker muscular dystrophy.