FDA OKs Trial of NGN-101 Gene Therapy in CLN5 Patients

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by Steve Bryson, PhD |

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The U.S. Food and Drug Administration (FDA) has cleared Neurogene’s request to conduct a Phase 1/2 clinical trial to evaluate the safety, tolerability, and efficacy of NGN-101, an investigational gene therapy to treat CLN5, a form of late-infantile Batten disease.

The therapy uses a harmless adeno-associated virus (AAV) to deliver a functional copy of the CLN5 gene, which is faulty in people with CLN5 Batten. Although the exact function of CLN5 is unclear, mutations in this gene lead to the buildup of waste products inside cells, causing damage. This can trigger seizures, progressive loss of motor and intellectual abilities, visual impairment, and premature death.

“NGN-101 is the first investigational gene therapy developed to address the devastating consequences of both neurodegeneration and vision loss in patients living with Batten disease,” Rachel McMinn, PhD, founder and CEO of Neurogene, said in a press release.

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“Importantly, we believe our preclinical data strongly support the potential of NGN-101 to stop the progression of CLN5 Batten disease, including the associated vision, motor, cognitive, and behavioral declines,” McMinn added.

According to the company, the trial — expected to begin in the first half of 2022 — will be an open-label, single-arm study to assess a single dose of NGN-101 delivered via injection into the fluid that surrounds the brain (intracerebroventricular administration) or into the eye (intravitreal administration). Neurogene also noted that the study will be the first to investigate a treatment for both neurodegeneration and vision loss in Batten.

The trial will be led by Jonathan W. Mink, MD, PhD, director of the University of Rochester Batten Center, in New York, which will serve as the primary trial site in the U.S.

“CLN5 is a devastating and rapidly progressive neurodegenerative disease in children that leads to vision loss, cognitive and motor impairment, seizures, and, ultimately, premature death,” Mink said. “This trial of NGN-101 will move research forward in developing a potentially disease-modifying treatment for CLN5 disease, providing hope to individuals and families where currently none exists.”

FDA clearance was supported by preclinical data demonstrating that NGN-101 treatment has the potential to slow or halt key features of disease progression, including vision loss, as well as motor, cognitive, and behavioral declines.

NGN-101 has received orphan drug designations by the FDA and European regulatory agencies. These designations provide incentives for therapy development, including assistance with trial protocols, lower regulatory fees, and a period of market exclusivity if approved.

“FDA clearance of our first [application] is an incredibly significant milestone for Neurogene and moves us one step closer to delivering on our mission to bring transformative treatments to patients living with rare neurologic diseases,” McMinn concluded.

Neurogene also is conducting a natural history study (NCT03822650) of CLN5, as well as CLN7, another form of late infantile Batten disease. This study, which is still enrolling CLN5 patients, is assessing the natural course of these diseases to determine the most important outcomes to measure in clinical trials.