Duchenne MD gene-editing therapy nets orphan drug designation
Study sought to see how PBGENE-DMD's preclinical results translate to humans
An experimental gene editing therapy for Duchenne muscular dystrophy (DMD) being developed by Precision Biosciences has received orphan drug status from the U.S. Food and Drug Administration (FDA).
The designation focuses on treatments for rare diseases like DMD. Its benefits include tax credits and fee exemptions, along with seven years of market exclusivity if the treatment is approved. Precision also recently won FDA rare pediatric disease status, another incentive for rare diseases.
“Receipt of orphan drug designation from the FDA for PBGENE-DMD underscores the tremendous unmet need and urgency to deliver safe treatments that significantly improve muscle function over time for boys living with Duchenne muscular dystrophy,” Cindy Atwell, chief development and business officer at Precision, said in a company press release.
DMD, the most common type of muscular dystrophy, is caused by mutations in the DMD gene that result in virtually no dystrophin, a protein that normally protects muscles from damage. Its loss leads to progressive muscle weakness and wasting, characteristic DMD symptoms.
Like many genes, DMD contains sections called exons. When strung together, exons in DMD provide cells with the instructions to make dystrophin. The aim of PBGENE-DMD is to edit genetic material to remove exons 45 to 55 from the gene. This leaves a shortened gene, but a nearly full-length version of dystrophin, according to the company. Precision estimates its therapy, which is administered once using a harmless virus to deliver its payload to muscle cells, will be applicable to up to 60% of people with DMD.
The therapy uses Precision’s gene-editing platform ARCUS that has advantages such as the type of DNA cut, its small size, and its simplicity, the company maintains.
Improved muscle function with gene-editing thrapy
In a mouse model, PBGENE-DMD produced long-term functional improvement, the company claims. Specifically, there was a significant increase in the amount of force that muscles could produce three and nine months after treatment. Between these two timepoints, the number of cells testing positive for dystrophin increased up to three times in certain muscles, including the leg, and the heart and diaphragm, which is crucial in breathing.
“This broad increase in dystrophin-positive cells, along with the increased dystrophin protein detected in tissues, further validates the improved muscle function that was observed over time,” said Cassie Gorsuch, PhD, Precision’s chief scientific officer, in a separate press release.
In satellite cells, a type of stem cell in muscle, the company found evidence PBGENE-DMD successfully edited the DMD gene. This may support long-term durability of the therapy’s impacts on muscle output and dystrophin production, according to Precision.
“We believe these results demonstrate the unique potential of the PBGENE-DMD gene-editing approach to produce a sustained functional benefit,” Gorsuch said.
The company hopes, with its orphan drug designation, to begin a clinical trial to examine how preclinical results translate to humans. “This regulatory milestone builds on our recent receipt of rare pediatric disease designation and, together with our preclinical body of evidence, gives us tremendous confidence as we move this program toward the clinic,” Atwell said. “Looking ahead, we remain in active dialogue with the FDA as we advance PBGENE-DMD toward regulatory milestones, with clinical data anticipated in 2026.”
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