Clinical-stage biotechnology company PepGen Inc. has been working to make a difference for people living with severe neuromuscular and neurological diseases. One of the conditions that PepGen is studying is Duchenne muscular dystrophy (DMD). The company has developed PGN-EDO51, in investigational compound described by Parent Project Muscular Dystrophy (PPMD) as:

an exon skipping therapy bound to a peptide to help the therapy reach the muscle cells. PGN-EDO51 targets those amenable to exon 51 skipping.

Exon 51 skipping is a therapeutic target for around 13% of all people living with Duchenne muscular dystrophy. So far, the therapy showed promise in preclinical studies. PGN-EDO51 led to greater exon skipping, which could lead to heightened dystrophin production. Further, a Phase 1 clinical study using healthy volunteers also showed significantly heightened exon skipping when compared to other oligonucleotide therapies. PGN-EDO51 is still being evaluated in the Phase 2 CONNECT1 study and will move into the Phase 2 CONNECT2 study at some point in 2024.

The U.S. Food and Drug Administration (FDA) seems to see the potential benefits of PGN-EDO51. A news release in Markets Insider shared that the FDA recently granted both Orphan Drug and Rare Pediatric Disease designations to PGN-EDO51 for DMD. Orphan Drug designation is granted to drugs or biologics intended to treat rare conditions affecting fewer than 200,000 people nationwide. Rare Pediatric Disease designation is granted to therapies designed for rare conditions in pediatric populations (ages 0-18). Both of these designations come alongside benefits for drug developers. Orphan Drug designation comes alongside fee waivers, tax credits, increased FDA communication, and 7 years of market exclusivity if/when the drug is approved. Rare Pediatric Disease designation comes with eligibility for a Priority Review Voucher (PRV).

What to Know: Duchenne Muscular Dystrophy (DMD)

Duchenne muscular dystrophy is a rare genetic disorder that leads to progressive muscle weakness and wasting. DMD results from mutations on the X chromosome. These mutations prevent the body from creating enough dystrophin, a protein that maintains the structure and membrane of muscle cells. Because DMD is an X-linked condition, it occurs significantly more frequently in males than females. DMD occurs in 1 in every 3,500 male births and 1 in every 50 million female births. Symptoms of Duchenne muscular dystrophy typically manifest in early childhood between ages three and six. These symptoms may include:

• Progressive muscle weakness that begins in the legs, thighs, and pelvis before moving throughout the rest of the body
• Enlarged calf muscles
• Toe-walking
• Frequent tripping and falling
• Difficulty moving positions, climbing stairs, walking, or rising from a sitting position
• Fatigue
• A “waddling” gait
• Scoliosis or lordosis
• Joint contractures
• Cardiomyopathy
• Reduced bone density and increased risk of fractures
• Learning disabilities
• Progression to respiratory failure and heart disease

There are a number of treatments available for DMD. Elevidys is a gene therapy approved for children with DMD variants between ages 4-5. Amondys 45 is approved for people with DMD whose variant is amenable to exon 45 skipping. Additional treatments include Emflaza (for patients ages 5+), Vyondys 53 and Viltepso (for people whose condition is amenable to exon 53 skipping), Exondys 51 (for those whose condition is amenable to exon 51 skipping), corticosteroids, and supportive treatments such as physical therapy, surgery, and mobility aids.