Gene therapy SGT-003 wins FDA’s rare pediatric disease designation

INSPIRE Duchenne set to test therapy on boys, ages 4-7

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by Andrea Lobo |

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The U.S. Food and Drug Administration (FDA) has granted rare pediatric disease status to SGT-003, a next-generation gene therapy candidate for Duchenne muscular dystrophy (DMD) developed by Solid Biosciences.

The designation is given to therapies with the potential to prevent or treat rare diseases that primarily affect children and adolescents. If it’s approved, Solid may qualify for a priority review voucher when it seeks approval of another experimental treatment. The company may also sell or transfer the voucher. The decision follows the recent orphan drug designation granted to SGT-003 by the FDA.

“Solid’s receipt of Rare Pediatric Disease Designation for SGT-003 highlights the continuing need for transformational treatments for this devastating disease,” Bo Cumbo, Solid’s president and CEO, said in a company press release.

DMD is caused by mutations in the DMD gene, which provides instructions to make dystrophin, a protein that acts as a shock absorber in muscle cells, protecting muscles from damage when they contract. Lack of dystrophin leads to progressive muscle weakness and wasting.

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SGT-003 delivers a gene encoding a functional yet shorter version of the dystrophin protein, called microdystrophin, to muscle cells. Using a new viral vector that contains a specifically designed capsid, or viral shell, should improve delivery to muscle cells, but not other cell types.

Solid plans to activate study sites for a Phase 1/2 trial called INSPIRE Duchenne (NCT06138639) this month. Patient screening should soon follow and dosing is anticipated by June, at the latest. The trial will test the safety and efficacy of SGT-003 in children with DMD, ages 4-7.

Initial safety results for the first three to four enrolled patients are anticipated by midyear and efficacy data from them is expected later this year.

In INSPIRE Duchenne, which is estimated to enroll six boys, SGT-003 will be administered as a single infusion into the vein, or intravenously. All the patients will receive the experimental therapy and will be followed for five years. The trial will start by dosing a first group, ages 4-5. A second group, ages 6-7, will be dosed after a subset of the first group is monitored.

The main goal is to assess side effects that started or worsened after treatment. The levels of microdystrophin protein in muscle about three months and a year after treatment, along with patient motor function a year into gene therapy, will be evaluated as a secondary measure.

Studies using human cell lines and a mouse model of DMD have shown that SGT-003 increases the gene activity, or expression, of microdystrophin, compared with the viral shell used for the first-generation candidate SGT-001.

“Preclinical data suggests that SGT-003 has potential to significantly improve on existing treatments for Duchenne by using a muscle tropic [directed] proprietary capsid to deliver a DNA sequence encoding a shortened form of the dystrophin protein which, importantly, includes the nNOS [neuronal nitric oxide synthase] binding domain,” said Gabriel Brooks, MD, chief medical officer at Solid. “nNOS is believed to play a crucial role in both muscular function and endurance.”

Data from a Phase 1/2 trial dubbed IGNITE DMD (NCT03368742), which is evaluating SGT-001 in boys with DMD, indicates the therapy led to sustained improvements in motor and lung function.