#313 Becker Muscular Dystrophy Clinical Trials with Edgewise Therapeutics

2024/11/1

DNA Today: A Genetics Podcast

Joanne Donovan

Joanne Donovan: Edgewise Therapeutics是一家专注于肌肉生物学的公司，致力于研发治疗贝克尔型和杜氏型肌营养不良症的药物。公司正在进行一项关键性III期临床试验（Grand Canyon研究），以评估sevasemten治疗贝克尔型肌营养不良症的疗效和安全性。Sevasemten是一种快速肌球蛋白抑制剂，通过轻微抑制肌球蛋白收缩来防止肌肉过度损伤，从而保护肌肉。早期研究显示sevasemten可以改善贝克尔型肌营养不良症患者的某些症状，例如痉挛和耐力，并能使North Star步行评估结果稳定甚至有所改善。Grand Canyon研究是一项为期18个月的双盲、随机、安慰剂对照试验，旨在评估sevasemten的疗效和安全性，纳入18-50岁、具有肌营养不良蛋白基因突变且North Star步行评估分数在一定范围内的男性患者。研究的排除标准包括：左心室射血分数低于40%、正在服用其他研究药物、肺功能差等。Sevasemten的常见副作用包括头晕和嗜睡，通常在服药几周后减轻。Edgewise Therapeutics提供旅行和其它费用支持以方便患者参与研究。公司与学术机构和倡导组织合作，开展社区教育和参与活动，以提高人们对贝克尔型肌营养不良症的认识。

Deep Dive

Key Insights

What is Becker Muscular Dystrophy (Becker)?

Becker is a genetic, progressive disease causing muscle degeneration and weakness due to dysfunctional dystrophin protein, which protects muscles during contraction. Symptoms typically begin in middle childhood, around age 9, and lead to loss of muscle function over time.

How does Becker Muscular Dystrophy differ from Duchenne Muscular Dystrophy (DMD)?

In Becker, the dystrophin protein is present but dysfunctional, while in DMD, it is entirely absent. Becker is often considered milder, but it still leads to significant muscle weakness and loss of function, with 30-40% of patients requiring a wheelchair by their late 40s.

What role does sevasemten play in treating Becker Muscular Dystrophy?

Sevasemten is an investigational fast myosin inhibitor designed to reduce contraction-induced muscle injury by slightly limiting muscle contraction. This helps protect muscle fibers from damage, potentially stabilizing or improving muscle function.

What are the key findings from Edgewise Therapeutics' earlier trials with sevasemten?

In a two-year open-label study, patients treated with sevasemten showed stabilization of muscle function, as measured by the North Star Ambulatory Assessment. Some patients even improved, and biomarkers of muscle damage decreased, indicating reduced muscle deterioration.

What is the Grand Canyon Study, and who is eligible to participate?

The Grand Canyon Study is a pivotal Phase 2 trial enrolling ambulatory adult men (18-50 years) with Becker Muscular Dystrophy. Participants must have a mutation in the dystrophin gene and a North Star score within a specific range to ensure the study can detect meaningful differences.

What are the inclusion and exclusion criteria for the Grand Canyon Study?

Inclusion criteria include having Becker Muscular Dystrophy, a dystrophin gene mutation, and a North Star score within a specific range. Exclusion criteria include low ejection fractions (below 40%), use of other investigational agents, or poor pulmonary function.

What are the common side effects of sevasemten observed in clinical trials?

The most common side effects reported are dizziness and sleepiness, which typically occur in the first few weeks of treatment and tend to diminish over time.

How does Edgewise Therapeutics support patients participating in their clinical trials?

Edgewise offers a concierge travel service to cover travel costs and other expenses, aiming to make participation cost-neutral for patients. They also provide a small stipend and support for childcare if needed.

Why is it important to have a placebo-controlled study for sevasemten?

A placebo-controlled study is crucial to determine if sevasemten is effective in slowing or reversing muscle deterioration. Without a placebo group, it would be difficult to attribute any improvements to the drug rather than natural disease progression or other factors.

What is the North Star Ambulatory Assessment, and why is it used in the Grand Canyon Study?

The North Star Ambulatory Assessment is a functional test that evaluates 17 daily living activities, such as climbing stairs, running speed, and getting up from a chair. It is used to measure changes in muscle function over time in the Grand Canyon Study.

Chapters

Becker muscular dystrophy is a genetic disease causing progressive muscle degeneration and weakness. Symptoms vary but can be debilitating, impacting daily life and mobility. The condition is caused by dysfunctional dystrophin, a protein crucial for muscle protection during contraction.

Becker MD is a genetic disease affecting dystrophin protein function.
Symptoms usually appear in the middle childhood years.
The disease leads to progressive muscle weakness and loss of function, potentially resulting in wheelchair dependence.

Shownotes Transcript

Dr. Joanne Donovan, Chief Medical Officer at Edgewise Therapeutics, join the show to discuss Becker Muscular Dystrophy (Becker) and emerging treatments.

We dive into Dr. Donovan’s role at Edgewise and the company’s research into treatments for Becker and Duchenne Muscular Dystrophy. At the forefront of this research is sevasemten, an investigational fast myosin inhibitor designed to combat contraction-induced muscle injury, which plays a significant role in muscle deterioration for those living with Becker.

Please note that sevasemten is an investigational agent that is not approved for use by any regulatory authority in any territory. All information shared in this podcast episode is intended for healthcare providers only. This episode is for informational purposes only and should not be considered professional medical advice. Always consult your doctor or qualified medical professional for any questions that you may have regarding a medical condition, procedure, treatment or trial.

Joanne M. Donovan, M.D., Ph.D., has served as Chief Medical Officer at Edgewise Therapeutics since 2021. Most recently, Dr. Donovan served as Chief Medical Officer and Senior Vice President, Clinical Development at Catabasis Pharmaceuticals. Since 1989, she has been a staff physician at the VA Boston Healthcare System, where she was formerly Chief of Gastroenterology. Dr. Donovan has held an appointment at Harvard Medical School since 1990, most recently as associate clinical professor of medicine. From 1998 to 2011, Dr. Donovan served in positions of increasing responsibility, ultimately as vice president of clinical development, at Genzyme, a biotechnology company, which she joined through its acquisition of GelTex Pharmaceuticals. Dr. Donovan holds a Ph.D. in medical engineering and medical physics from the Massachusetts Institute of Technology, an M.D. from Harvard Medical School and an S.B. from the Massachusetts Institute of Technology. She completed residency training in internal medicine and a fellowship in gastroenterology at the Brigham and Women's Hospital.'

Key Discussion Points:

Becker Muscular Dystrophy Overview: Becker is a genetic, progressive disease that leads to muscle degeneration and weakness. Symptom onset varies and can be debilitating, with patients losing muscle function over time.

The Science Behind Becker: Muscle breakdown in Becker is driven by dysfunctional dystrophin, a protein that supports muscle fibers during contraction. Without proper dystrophin function, repeated contraction-induced injury leads to muscle fiber loss and replacement by fibrosis and fat.

Edgewise Therapeutics’ Research: The investigational therapy sevasemten has shown promising results in recent trials, including stabilization of functional assessments and reductions in muscle damage biomarkers. Dr. Donovan shares how Edgewise is progressing to the pivotal Phase 2 GRAND CANYON study, which is now enrolling ambulatory adults with Becker.

If you are a healthcare provider with patients who may benefit from this research, you can refer them to the study through the information below.

Contact our Edgewise team by email at [email protected]).
Have your patient go to beckergcstudy.com), where they can contact someone from patient support.
Or submit your contact information via beckergcstudy.com/hcp) and someone will reach out to you.

More DNA Today Episodes on Muscular Dystrophies:

#156 Rich Horgan on Duchenne Muscular Dystrophy (DMD))

#202 Duchenne Muscular Dystrophy with Ann Martin and Madhuri Hegde)

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