RARE Daily

Duchenne Patient Groups Collaborate on Re-Dosing Gene Therapy for DMD

June 16, 2023

Rare Daily Staff

CureDuchenne, the Muscular Dystrophy Association, and Parent Project Muscular Dystrophy are collaborating on a clinical trial grant to test repurposing of Argenx’s FDA-approved drug Vyvgart for its potential to reduce antibodies to adeno-associated virus in patients with Duchenne muscular dystrophy.

The three organizations provided $100,000 each to sponsor a one-year clinical study to assess the safety and efficacy of Vyvgart to lower AAV antibodies precluding DMD patients from gene therapy.

Duchenne muscular dystrophy (DMD) is a rare and progressive genetic muscle disease caused by the lack of a critical membrane-stabilizing protein called dystrophin, which results in muscle degeneration and weakness. DMD symptom onset is in early childhood, usually between ages 2 and 3. The disease primarily affects boys, but in rare cases it can affect girls. In Europe and North America, the prevalence of DMD is approximately six per 100,000 individuals. Doctors often diagnose the disease between ages 3 and 6 when children show early signs of significant muscle weakness, such as delayed ability to sit, stand, or walk and difficulties learning to speak. Over time, DMD becomes fatal as muscle degeneration disrupts lung and heart function. There is no cure for DMD, however, lifespans have been extended and quality of life has been improved for many through physical therapy and medications to address certain symptoms.

Gene replacement therapy for DMD has long been an attractive therapeutic prospect in targeting the root cause of the disease, with the aim of restoring dystrophin protein function. Several companies including Sarepta, Solid Biosciences, Pfizer, and Regenxbio have undertaken clinical trials with truncated dystrophin constructs for gene therapy. This co-funded clinical trial aims to suppress anti-AAV antibodies in a subset of DMD patients who are currently not eligible for gene therapy due to pre-existing AAV antibodies from natural infections. The trial will also explore the potential for reducing in DMD patients anti-AAV antibodies acquired from previous participation in gene therapy trials in order to enable future redosing efforts.

Vyvgart is an approved drug currently used to treat autoimmune diseases by reducing overall levels of circulating IgG antibodies. The FDA approved Vyvgart to treat generalized myasthenia gravis. The study will investigate whether Vyvgart has the ability to reduce AAV antibodies to levels compatible with safe and effective delivery of gene therapies in DMD patients. Positive results from this study may be applicable to the translation of AAV gene therapies for other neuromuscular diseases.

The trial is an open-label, single center, multi-arm, phase II study to take place at Powell Center for Rare Disease Research and Therapy, located in Gainsville, Florida. A total of 12 DMD patients will participate in the study – six with elevated anti-AAV titers prior to gene therapy and six with elevated titers post-gene therapy. The primary outcome of the study will be to assess the ability of Vyvgart to lower anti-AAV capsid antibody pre and post exposure to AAV. The secondary outcome of the study will be to determine safety and tolerability of Vyvgart in boys with DMD.

“We are just beginning to realize the impact of gene therapies that can treat the underlying root cause of genetic diseases,” said study leader Barry Byrne, MDA chief medical advisor, associate chair of pediatrics, and director of the Powell Gene Therapy Center at the University of Florida. “Disease-modifying therapies are no longer a thing of the future. Our goal now is to figure out how to best maximize and achieve the biggest impact with the technology in our hands.”

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