Repurposed Myasthenia Gravis Drug May Allow for Redosing of AAV Vector-Based Gene Therapies

This is the second part of an interview with Barry J Byrne, MD, PhD. For the first part, click here.

Barry J Byrne, MD, PhD
Credit: MDA

One of the drawbacks of adeno-associated virus (AAV) vector-based gene therapies is that patients may have preexisting immunity to the vectors used, thus posing potential risks to the safety and efficacy of the product for these patients. Furthermore, patients may develop antiAAV antibodies after treatment with current AAV vector-based gene therapies, preventing potential future redosing or treatment with other AAV vector-based gene therapies.

Barry J Byrne, MD, PhD, the chief medical advisor of the Muscular Dystrophy Association (MDA) and a physician-scientist at the University of Florida, and his colleagues are currently researching a solution to this obstacle. In the context of a larger interview about the upcoming 2024 MDA Clinical & Scientific Conference, which will be held from March 3-6 in Orlando, Florida, CGTLive™ asked Byrne about the details of this research.

CGTLive: What is your current focus in research?

Barry J Byrne, MD, PhD: Since the beginning of the MDA there has been a strong emphasis on research, with a total of over $1 billion in research funding to investigatorssince the formation of the association. Particularly in the area of gene therapy, there's been a very strong commitment of the MDA with over 80 new grant awards in 2022 and a significant amount of funding towards gene therapy research. One of the things that we've been investigating with the support of the MDA is how to sustain the effect of what are transformative therapies, particularly in Duchenne muscular dystrophy. That involves mechanisms to minimize immune response and improve safety of gene therapy products, as well as the potential to top off the effects or potentially make accessible for patients new therapies when they become available.

Can you tell us more about your redosing trial?

We've been particularly interested in understanding the eligibility for gene therapy and the relationship of antibody levels—preexisting antibodies and those that develop after exposure to gene therapy—to maximize the effect, enhance safety, and improve eligibility for access to gene therapy treatments. One of the concerns in the patient communityis that the gene therapy may be inaccessible to them because of prior environmental exposure to AAV or related parvoviruses. Therefore, we've been able to test the idea that a drug used for myasthenia gravis known as Vyvgart or efgartigimod alfa can be used to lower total Immunoglobulin G levelsand therefore reduce the AAV-specific antibodies or anticapsid antibodies that might exclude someone from access to gene therapy.

This study is supported by the MDA, Parent Project Muscular Dystrophy, and CureDuchenne. We've been working with the sponsor who manufactures Vyvgart to file additional documents with the FDA to begin the study in the next few months.

This transcript has been edited for clarity.

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