FDA Extends Review of Gene Therapy for Rare Immune Disorder

The FDA has extended the priority review period for Rocket Pharmaceuticals’ biologics license application (BLA) for Kresladi (marnetegragene autotemcel or RP-L201) to treat the rare, autosomal recessive pediatric disease leukocyte adhesion deficiency-I (LAD-I). The application is being delayed by three months for regulators to review clarifying chemistry, manufacturing, and controls (CMC) information submitted by Rocket. The new Prescription Drug User Fee Act (PDUFA) date is now June 30, 2024.

Severe leukocyte adhesion deficiency-I is caused by mutations in the ITGB2 gene that encodes for CD18, a key protein that facilitates the immune response against infections. As a result, white blood cells (leukocytes) do not function normally. Children with this disease experience life-threatening bacterial and fungal infections that respond poorly to antibiotics. Children who survive infancy experience recurrent severe infections including pneumonia, gingival ulcers, necrotic skin ulcers, and septicemia. LAD-I is estimated to impact an estimated 800 to 1,000 children in the United States and Europe.

Kresladi is a lentiviral vector-based investigational gene therapy. It contains autologous hematopoietic stem cells that have been genetically modified to deliver a functional copy of the ITGB2 gene. Data from the global phase 1/2 study demonstrated 100% overall survival at 12 months post-infusion (and for the entire duration of follow-up) for all nine LAD-I patients with 12 to 24 months of available follow-up.

Data also showed large decreases compared with pre-treatment history in the incidences of significant infections. All primary and secondary endpoints were met, and the therapy was well tolerated in all patients with no treatment related serious adverse events.