The FDA has extended the priority review period for the Biologics License Application (BLA) of Kresladi, an investigational gene therapy designed to treat severe Leukocyte Adhesion Deficiency-I (LAD-1). The initial deadline of March 31, 2024, has been pushed to June 30, 2024, to allow regulators to review additional information related to chemistry, manufacturing, and controls (CMC).
Severe Impacts of LAD-1 and Current Treatment Challenges
LAD- 1 is a rare, autosomal recessive pediatric disease resulting from mutations in the ITGB2 gene. CD18, a key protein encoded by ITGB2, plays a crucial role in the immune response, and its deficiency leads to severe and life-threatening infections, especially in infancy.
LAD-1 patients face recurrent and life-threatening bacterial and fungal infections during infancy, often unresponsive to antibiotics. Survival beyond childhood without a successful bone marrow transplant is rare, and the current potential curative treatment, an allogeneic hematopoietic stem cell transplant, poses significant morbidity and mortality risks. With an estimated 800 to 1,000 individuals impacted in the U.S. and Europe, there is a high unmet medical need for effective treatments for severe LAD-1.
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RP-L201: A One-Time Investigational Gene Therapy
Kresladi, also known as marnetegragene autotemcel or RP-L201, is a lentiviral vector-based gene therapy designed to address LAD-1. RP-L201 offers a potential breakthrough as a one-time investigational gene therapy. It involves modifying patient-derived hematopoietic stem cells with a lentiviral vector to deliver a functional copy of the ITGB2 gene, addressing the deficiency of the CD18 protein. The therapy has received various designations, including FDA Regenerative Medicine Advanced Therapy (RMAT), Rare Pediatric, and Fast Track designations in the U.S., and PRIME and Advanced Therapy Medicinal Product (ATMP) designations in the EU.
RP-L201's lentiviral vector resulted from a collaboration between University College London (UCL) and the Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT).
Priority Review Voucher Eligibility and Positive Clinical Data
The pharmaceutical company could be eligible for a Priority Review Voucher if RP-L201 gains approval. The submission is supported by data from a global phase 1/2 study, demonstrating 100% overall survival at 12 months post-infusion for all nine patients with 12 to 24 months of available follow-up. The study also revealed significant decreases in infection rates, resolution of LAD-I-related skin lesions, and restoration of wound repair capabilities.
The promising data were presented at the 26th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT) in May 2023, indicating a positive trajectory for the gene therapy in addressing the challenges of severe LAD-1.