Drug development within the rare disease space can be tricky. In many cases, there is a general lack of research and understanding around these conditions; as a result, many companies choose to develop therapies for better-known conditions. The Orphan Drug Act sought to mitigate this by creating Orphan Drug Designation. This status, granted to drugs or biologics intended to treat, prevent, or diagnose rare conditions, comes alongside incentives such as fee waivers, tax credits, and seven years of market exclusivity upon drug approval. According to recent reporting from Muscular Dystrophy News, the FDA granted Orphan Drug and Rare Pediatric Disease designations to DYNE-251 for the treatment of Duchenne muscular dystrophy (DMD).
DYNE-251 is an exon-skipping therapy (allowing for the skipping of exon 51) that consists of phosphorodiamidate morpholino oligomers (PMOs) that promote exon skipping in the nucleus and provide more targeted muscle delivery. Developed by Dyne Therapeutics, DYNE-251 was created using the proprietary FORCE platform. The therapy helps to create a truncated but still functional version of dystrophin—the protein that is missing or deficient in DMD—to halt or even reverse disease progression. In both murine and non-human primate models, DYNE-251 achieved exon skipping, improved muscle strength and function, and reduced muscle damage.
Now, Dyne Therapeutics is evaluating the safety, efficacy, tolerability, and pharmacokinetics of DYNE-251 in the Phase 1/2 DELIVER study. 46 boys with DMD have enrolled. Within the study, participants will receive either varying DYNE-251 doses or a placebo for a 24-week period with an open-label period of 24-weeks.
What is Duchenne Muscular Dystrophy (DMD)?
As described above, people with Duchenne muscular dystrophy have missing or deficient dystrophin protein. This protein normally plays a role in muscle strength and function. When it is missing or deficient, the muscle becomes weakened and atrophied. It is exceedingly rare for females to have DMD; only around 1 in every 50 million females are born with this condition. It occurs in 1 in every 3,500 males as the disease is inherited in an X-linked recessive pattern and passed on maternally. Symptoms of DMD often appear before a child’s 6th birthday. Because it is progressive, symptoms will worsen over the years; many people use mobility aids such as wheelchairs by the time they are teenagers. Symptoms of DMD may include:
- Difficulty walking, climbing, standing from a seated position, or moving positions
- Progressive muscle weakness that often manifests in the legs, thighs, and pelvis
- Abnormal enlargement of the calves
- A waddling gait
- Frequent falling
- Joint contractures
- Increased risk of bone fractures
- Learning disabilities
- Scoliosis or lordosis (abnormal spinal curvature)