Gene Therapy for Rare Immune Disorder Gets FDA Review Date

The FDA has accepted the biologics license application (BLA) and granted priority review for RP-L201 (marnetegragene autotemcel) to treat children with severe Leukocyte Adhesion Deficiency-I (LAD-I). The agency has assigned a review date of March 31, 2024.

Severe Leukocyte Adhesion Deficiency-I (LAD-I) is a rare genetic immune disorder that can lead to serious and life-threatening bacterial and fungal infections beginning shortly after birth. Many children don’t survive past infancy. It occurs in about one per 1 million people worldwide. LAD-I is estimated to impact an estimated 800 to 1,000 children in the United States and Europe.

LAD-I is caused by mutations in the ITGB2 gene, which provides instructions for making the protein beta-2 integrin component CD18. CD18 is a key protein that contributes to immune response to infections. Currently the only potential curative treatment is an allogeneic hematopoietic stem cell transplant,

Developed by Rocket Pharmaceuticals, RP-L201 is a one-time gene therapy that contains autologous (patient-derived) hematopoietic stem cells that have been genetically modified with a lentiviral vector to deliver a functional copy of the ITGB2 gene. Rocket holds FDA regenerative medicine advanced therapy (RMAT), rare pediatric, and Fast track designations.

The submission is based on data from the global phase 1/2 study, which demonstrated 100% overall survival at 12 months post-infusion of RP-L201 for all nine 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, as well as resolution of LAD-I-related skin lesions and restoration of wound repair capabilities. RP-L201 was very well tolerated in all patients with no treatment-related serious adverse events.

Donald B. Kohn, M.D.

These data were presented at the 26th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT) in May 2023.

“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. Based on what I see, they are all experiencing a normal childhood life, which is the goal of this type of potentially curative gene therapy,” Donald B. Kohn, M.D., said in a press release. He is 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.

This story first appeared on Formulary Watch.