Sarepta adds experimental gene therapy to its pipeline

MD Matters

Sarepta Therapeutics has licensed an experimental gene therapy for a type of muscular dystrophy developed by scientists at Nationwide Children's Hospital in Columbus, Ohio. Nationwide Children's Hospital (formerly Columbus Children's Hospital) is a nationally ranked pediatric acute care teaching hospital.

Sarepta struck the deal with Nationwide two years ago to secure an exclusive option for the gene therapy. The agreement came after the completion of preclinical and safety studies that Sarepta said had demonstrated "early proof of concept" for the treatment.

As Ned Pagliarulo reported in BioPharma Dive, “The gene therapy is designed to treat a common form of limb-girdle muscular dystrophy, a severe neuromuscular disease that leads to progressive weakness in the limbs and around the hips and shoulders. The type targeted by Nationwide's treatment, Type 2A, is caused by mutations in the CAPN-3 gene and is considered the most common form of limb-girdle.”

Sarepta, which has one of the larger pipelines in biotech, has 42 different programs listed by the developer. Of those, twenty-six are gene replacement therapies for a range of muscular dystrophies as well as lysosomal storage disorders and diseases of the nervous system. Most of these programs are in the preclinical or early clinical stages of development.

Nationwide Children's Hospital has been involved as a partner and source for those programs, including the Duchenne muscular dystrophy treatment that is at the present time the most valued and closely watched gene therapy Sarepta is developing. Nationwide, which has been a hub for gene therapy research, has spun out several biotech companies, including AveXis, the developer of the spinal muscular atrophy treatment Novartis now sells as Zolgensma, and Myonexus, a startup acquired by Sarepta in 2019. 

The Ohio hospital has also built out its manufacturing capabilities, starting a subsidiary called Andelyn Biosciences that has the objective of producing gene therapy components for biotech and pharmaceutical companies. In creating Andelyn, Nationwide aims to build on its decade-long experience in developing, testing and manufacturing gene therapies for deadly inherited diseases like spinal muscular atrophy and Duchenne muscular dystrophy.

Zarife Sahenk, a neruologist at Nationwide, led the preclinical research supporting the limb-girdle gene therapy Sarepta has licensed. The prospective treatment is built around the same type of uninfectious virus that Sarepta uses to deliver functional genes with its Duchenne treatment and five others that it is developing for different forms of limb-girdle muscular dystrophy. By licensing the treatment, Sarepta hopes to "build off the knowledge we gained" from those other programs, according to Louise Rodino-Klapac, the company's chief scientific officer and the former head of a gene therapy lab at Nationwide. 

Sarepta said that more than 70 percent of limb-girdle muscular dystrophy cases would be addressed by the six gene therapies it now owns and is developing. The most advanced of those candidates, which is known as SRP-9003, targets Type 2E. Early results from a handful of patients demonstrate that treatment has led to increased production of the protein missing in the disease and resulted in functional gains in the therapy.