Advocacy groups launch clinical trial to improve gene therapy access

The study will test whether efgartigimod would benefit more DMD patients

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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A circle of hands is shown as a show of unity.

Three advocacy organizations are teaming up to run a clinical trial to test if efgartigimod, an approved treatment for certain autoimmune diseases, might let more people with Duchenne muscular dystrophy (DMD) benefit from gene therapies.

CureDuchenne, Muscular Dystrophy Association (MDA), and Parent Project Muscular Dystrophy (PPMD) are each contributing $100,000 to run the one-year study, which will be led by MDA’s chief medical advisor Barry Byrne, MD, PhD.

“We are grateful to the Muscular Dystrophy Association, Parent Project Muscular Dystrophy, and CureDuchenne for this funding, which lets us test novel strategies to ensure that gene therapy is as inclusive as it can be,” Byrne, the director of the Powell Gene Therapy Center at the University of Florida, said in a press release.

“Our three organizations came together in recognition of the importance of strategizing for as many DMD patients to be eligible for gene therapy as possible,” said Sharon Hesterlee, PhD, chief research officer at the MDA.

DMD is caused by mutations in the gene that provides instructions for making the muscle protein dystrophin. As a result, no dystrophin is produced. With gene therapy a working copy of the gene is delivered to muscle cells, letting them make a functional version of the protein.

The U.S. Food and Drug Administration (FDA) is set to decide this week whether to grant accelerated approval to SRP-9001, a gene therapy for DMD developed by Sarepta Therapeutics. If it’s approved, it would become the first commercially available gene therapy for DMD.

“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,” Byrne said. “Our goal now is to figure out how to best maximize and achieve the biggest impact with the technology in our hands.”

Like gene therapies approved for other conditions, SRP-9001 delivers its genetic payload to cells using a modified virus, specifically a form of adeno-associated virus (AAV), which is commonly used because it’s easy to manipulate in a lab and doesn’t cause disease in humans.

As with any virus, when a person encounters AAV in the world, his immune system will make antibodies that neutralize and eliminate it. Some antibodies will stick around, so if the same virus is encountered in the future, the immune system can eliminate it more efficiently. This is the principle that makes vaccines work.

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Effect of efgartigimod on anti-AAV antibodies

When a person with preexisting antibodies against AAV receives a gene therapy with the same virus, the anti-AAV antibodies will respond to the gene therapy like it’s a virus, neutralizing it and rendering it ineffective.

As such, patients with preexisting antibodies against AAV are generally not eligible for these gene therapies. For example, the Phase 3 EMBARK (NCT05096221) trial of SRP-9001 is only open to patients who don’t have elevated levels of antibodies against the form of AAV used in this gene therapy.

“Gene therapy delivered by AAV represents a potentially transformative therapy for patients, but some individuals are barred from accessing these AAV delivered therapies due to preexisting antibodies,” said Eric Camino, PhD, vice president of research and clinical innovation at PPMD.

The upcoming trial will test whether efgartigimod can reduce levels of anti-AAV antibodies, which may let more patients access AAV-based gene therapies.

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

Efgartigimod is designed to reduce antibodies by blocking the activity of a protein that helps to stabilize their levels in the blood. It’s approved to treat myasthenia gravis, an autoimmune disorder driven by antibodies that target the communication between nerve cells and muscles. It’s marketed by Argenx under the brand name Vyvgart.

“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 preexisting antibodies to be dosed,” Camino said.

“Should an approved drug be able to reduce AAV antibodies to acceptable levels it would serve as an efficient way to open doors for patients who are currently ineligible for gene therapy,” Hesterlee added. “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.”