The FDA has issued a complete response letter to the new drug application (NDA) for drisapersen (Kyndrisa, BioMarin Pharmaceutical Inc.) for the treatment of patients with Duchenne muscular dystrophy amenable to exon 51 skipping.
The FDA issues complete response letters to indicate that an application is not ready for approval in its present form. The FDA concluded that the standard of substantial evidence of effectiveness had not been met for drisapersen.
Duchene muscular dystrophy is an x-linked genetic disorder that affects mostly boys. In the disease, boys begin to show signs of muscle weakness as early as 2 to 5 years of age. The disorder gradually weakens the skeletal or voluntary muscles in the arms, legs, and trunk. Because of progressive muscle weakness, Duchenne patients are often wheelchair bound between the ages of seven and 13 years. At a later stage, the boys’ respiratory and cardiac muscles are also affected, and for most boys, respiratory and cardiac failures are major causes of death, often prevalent by the age of 20.
Duchenne affects approximately 1 in every 3,500 to 5,000 male children, making it the most common fatal genetic disorder diagnosed in childhood. There is no FDA-approved therapy designed specifically to treat Duchenne.
Ongoing drisapersen extension studies will continue, as will ongoing clinical trials for other exon-skipping oligonucleotides (BMN 044, BMN 045, and BMN 053), while BioMarin explores the next steps for the rejected NDA. Patients currently receiving drisapersen, BMN 044, BMN 045, or BMN 053 will remain on therapy.
Drisapersen is an antisense oligonucleotide that induces exon skipping to provide a molecular patch for dystrophin transcripts produced by certain mutated dystrophin genes. Exons are the parts of a gene that contain the instructions for generating a protein. In applicable cases, skipping an exon near the mutation allows the production of a truncated but functional dystrophin protein.
Source: Biomarin Pharmaceutical; January 14, 2016.