NS Pharma DMD treatment gets FDA rare pediatric disease status
Exon-skipping therapy set for Phase 1/2 trial in US, Japan
The U.S. Food and Drug Administration has granted rare pediatric disease designation to NS-050/NCNP-03, an exon-skipping Duchenne muscular dystrophy (DMD) treatment from NS Pharma.
Treatments granted this designation are aimed at serious or life-threatening diseases affecting children and fewer than 200,000 U.S. patients.
“We are grateful for this designation, which can help us accelerate the development of this therapy for Duchenne,” Yukiteru Sugiyama, PhD, NS Pharma president, said in a company press release. “The journey from first symptom to diagnosis and finally treatment can be long and challenging for patients with rare diseases and their caregivers,” Sugiyama said.
DMD is caused by a lack of dystrophin, a protein that protects muscles from damage caused by contractions. The disease is characterized by progressive muscle weakness and wasting, usually first in the muscles around the hips and upper legs and later in other parts of the body.
The DMD gene contains instructions to produce dystrophin. Genes are constructed with information blocks called introns and exons. To produce a protein, an intermediary molecule called precursor messenger RNA (pre-mRNA) is formed to copy the information from the template gene. Introns are removed from the pre-mRNA, leaving the exons in the mature mRNA. Then the cell can follow the instructions in the orderly bound exons and build proteins.
DMD treatment skips exon 50
The integrity of introns and exons is crucial to obtaining correct, mature mRNA. If the necessary instructions to produce a healthy protein are incorrect or absent, the mature mRNA delivers the wrong building instructions and the cells build proteins of incorrect length and form that do not function properly.
Exon-skipping therapies get muscle cells to skip over one or more exons when the gene is read to make a protein, allowing production of a shortened, but functional, version of dystrophin. Four exon-skipping treatments are currently approved in the U.S. for DMD. One of these is Viltepso (viltolarsen), an exon 53-skipping therapy also marketed by NS Pharma.
NS-050/NCNP-03 is an antisense oligonucleotide, a short strand of genetic material. The therapy skips over exon 50, an approach amenable for about 4% of the DMD population. According to NS Pharma, NS-050/NCNP-03 aims to enable production of a functional yet slightly shorter dystrophin protein, which is expected to suppress muscle function deterioration.
The therapy will be assessed in a Phase 1/2 study called Meteor50 (NCT06053814), which will take place in Japan and the U.S. Participants will be DMD boys amenable to exon 50 skipping and able to walk. They will be treated with increasing doses of NS-050/NCNP-03 once weekly for 12 weeks, or a placebo. After this period, all boys will receive the exon-skipping therapy at a selected dose for 24 weeks (about six months).
Outcome measures include number and severity of adverse events, pharmacological assessments and quantification of dystrophin production.
As with Viltepso, NS050/NCNP-030 was discovered along with the National Center of Neurology and Psychiatry and Nippon Shinyaku, NS Pharma’s parent company.
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