MDA, CureDuchenne, PPMD Collaborate to Reduce AAV Antibodies to Enable Gene Therapy


The advocacy groups are funding a 1-year study to be led by Barry Byrne, MD, PhD, at University of Florida.

CureDuchenne, Muscular Dystrophy Association (MDA), and Parent Project Muscular Dystrophy (PPMD) have just announced their collaboration on a clinical trial grant to investigate redosing of AAV gene therapies in patients with Duchenne muscular dystrophy (DMD).

“Should an approved drug be able to reduce adeno-associated virus (AAV) antibodies to acceptable levels it would serve as an efficient way to open doors for patients who are currently ineligible for gene therapy. This approach could also possibly provide re-treatment options for patients who are starting to see a reduction in drug effect, although the hurdle would be higher there,” Sharon Hesterlee, PhD, chief research officer, MDA, said in the statement.

Each organization is granting $100,000 for the 1-year clinical trial at University of Florida (UF) to be led by Barry Byrne, MD, PhD, chief medical advisor, MDA, and associate chair, pediatrics and director, Powell Gene Therapy Center, UF. The open-label, single center, multi-arm, phase 2 trial will assess the safety and efficacy of efgartigimod alfa-fcab (Vyvgart) to lower AAV antibodies in patients with DMD that have pre-existing AAV antibodies from natural infections currently ineligible for gene therapy as well as in patients that have AAV antibodies from previous gene therapies for potential redosing.

“We are hopeful that this study will support a clinical strategy to effectively administer gene therapy to individuals with pre-existing AAV-neutralizing antibodies, who are currently excluded from treatment, and to help pave a path towards re-dosing individuals who have already received an AAV-delivered gene therapy,” Debra Miller, founder and CEO, CureDuchenne, added.

READ MORE: Genetic Medicine in DMD: End Points, Assessment, and Approvals

Vyvgart is currently FDA-approved to treat autoimmune diseases and reduces overall levels of circulating IgG antibodies. In patients with myasthenia gravis, it has been shown to reduce pathogenic acetylcholine receptor antibodies. If shown to be effective in reducing AAV antibodies in patients with DMD, data from the study may be translatable to other neuromuscular diseases.

“We are thrilled to be able to collaborate with CureDuchenne and MDA in order to fund meaningful research that could impact many individuals living with Duchenne,” Eric Camino, PhD, vice president, research and clinical innovation, PPMD, added. “Gene therapy delivered by AAV representsa potentially transformative therapy for patients, but some individuals are barred from accessing these AAV delivered therapies due to pre-existing antibodies. This research could create a pathway for broadening who can access AAV-mediated gene therapy; lowering the antibodies to AAV for a window of time could allow for individuals with pre-existing antibodies to be dosed.”

The study plans to evaluate Vyvgart in 12 male patients with DMD, 6 with preexisting AAV antibodies and 6 with AAV antibodies after gene therapy. The primary outcome will assess levels of anti-AAV capsid antibody pre and post exposure to AAV. The secondary outcome will be safety and tolerability.

"We are grateful to the MDA, PPMD, and CureDuchenne for this funding, which lets us test novel strategies to ensure that gene therapy is as inclusive as it can be," Byrne added. "We are just beginning to realize the impact of gene therapies that can treat the underlying root cause of genetic diseases. 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."

CureDuchenne, Muscular Dystrophy Association, and Parent Project Muscular Dystrophy announce collaborative project to focus on re-dosing gene therapy in Duchenne Muscular Dystrophy. News release. Muscular Dystrophy Association. June 15, 2023. Accessed June 16, 2023.
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