FDA Assigns Review Date for Gene Therapy for Rare Immune Disorder

The FDA has granted priority review for Rocket Pharmaceuticals’ biologics license application (BLA) for marnetegragene autotemcel (RP-L201) to treat the rare, autosomal recessive pediatric disease leukocyte adhesion deficiency-I (LAD-I). Regulators set a Prescription Drug User Fee Act (PDUFA) date set of March 31, 2024.

Severe leukocyte adhesion deficiency-I is a 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.

Marnetegragene autotemcel 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 of marnetegragene autotemcel 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.

Donald B. Kohn, M.D.,

“As the principal investigator in the United States, I oversaw treatment of six of the nine LAD-I patients in this trial. In my opinion, the results are remarkable. All of these children have been in good health with no significant LAD-I-related infections or inflammatory skin lesions since treatment,” Donald B. Kohn, M.D., distinguished professor of Microbiology, Immunology & Molecular Genetics, Pediatrics, and Molecular & Medical Pharmacology at University of California, Los Angeles (UCLA) and director of the UCLA Human Gene and Cell Therapy Program, said in a press release.

Data also showed large decreases compared with pretreatment history in the incidences of significant infections, combined with evidence of resolution of LAD-I-related skin lesions and restoration of wound repair capabilities. It was very well tolerated in all patients with no treatment-related adverse events.