Earlier this week, Sarepta Therapeutics announced that the FDA approved a New Drug Application (NDA) for Casimersen (SRP-4045). The treatment, for patients with exon 45 amenable Duchenne muscular dystrophy (DMD), would benefit the 8% of patients with this specific form of DMD. With Sarepta seeking accelerated approval, the FDA will fully respond with further regulatory action by February 25, 2021.
Duchenne Muscular Dystrophy (DMD)
Duchenne muscular dystrophy (DMD) is one of nine forms of muscular dystrophy, a genetic disorder causing muscle weakness and movement difficulties. In particular, patients with DMD lack dystrophin, a protein that plays a role in connecting muscle fibers to an extracellular matrix. Dystrophin also strengthens these fibers, protecting patients from injury. With an inability to create dystrophin, patients with DMD experience severe muscle weakness, heart and respiratory weakness, and quadriplegia. It occurs in males at a significantly higher rate than females. In most cases, symptom onset occurs in early childhood. Unfortunately, DMD is often fatal by mid- to late-20s. Symptoms include:
- Walking, moving, and balance difficulties
- Progressive muscle weakness that begins in the legs, pelvis, and thighs
- Heart disease
- Respiratory failure
- Muscle pain and stiffness
- Learning disabilities
- Difficulty swallowing
- Enlarged calf muscles
Learn more about DMD.
If approved, Sarepta Therapeutics will market casimersen under the name AMONDYS 45. The drug therapy is a phosphorodiamidate morpholino oligomer (PMO) specifically designed for patients with DMD whose genetic mutations are amenable to exon 45. It works by binding to dystrophin pre-mRNA and later excluding exon 45. As a result, patients can start producing some form of dystrophin.
Researchers explored the efficacy, safety, and tolerability of casimersen, as well as golodirsen (VYONDYS 53) in the Phase 3 ESSENCE study. Where patients with exon 45 amenable DMD received casimersen, those with exon 53 amenable DMD received golodirsen. The ESSENCE study is still ongoing. However, current data suggests casimersen significantly improves dystrophin production. Participants receive either a placebo or 300mg/kg intravenous casimersen or golodirsen for a 96 week (22 month) period. After, all patients will receive treatment for 48 weeks (11 months).
Currently, data on casimersen is still being collected. However, some adverse reactions were found for VYONDYS 53, suggesting researchers should keep an eye on the same potential problems for casimersen. These adverse reactions include:
- Abdominal pain
- Common cold
- Administration site and back pain
- Nausea, vomiting, and diarrhea
- Reduced renal function and/or renal toxicity
- Intense itching
- Ear infections