The US Food and Drug Administration has granted accelerated approval to marnetegragene autotemcel (KRESLADI) for pediatric patients with severe leukocyte adhesion deficiency-I due to biallelic variants in ITGB2 who do not have an available human leukocyte antigen-matched sibling donor for allogeneic hematopoietic stem cell transplant, according to a press release from Rocket Pharmaceuticals.

Severe leukocyte adhesion deficiency type I is a rare genetic immunodeficiency caused by variants in the ITGB2 gene, which encodes the CD18 protein involved in leukocyte adhesion to blood vessel walls and migration into tissues. Infants with the severe form experience recurrent bacterial and fungal infections that respond poorly to antimicrobial therapy and often require repeated hospitalizations. The condition is associated with high mortality in early childhood in the absence of treatment. In the US, the estimated incidence ranges from approximately one in 100,000 to one in 200,000 live births, with about two-thirds of affected patients classified as having the severe form of the disease.

Marnetegragene autotemcel is an autologous hematopoietic stem cell–based gene therapy indicated for pediatric patients without an available human leukocyte antigen–matched sibling donor for allogeneic hematopoietic stem cell transplant. The approval was based on observed increases in neutrophil CD18 and CD11a surface expression. Continued approval remains contingent on verification of clinical benefit through longer-term follow-up in an ongoing clinical study and a postmarketing registry.

“The approval of KRESLADI represents the culmination of many years of scientific research and clinical collaboration aimed at addressing the underlying cause of this devastating disease,” said Donald B. Kohn, MD, of the University of California, Los Angeles, principal investigator of the phase 1/2 study.

The safety profile includes risks associated with myeloablative conditioning and gene therapy, including serious infections, veno-occlusive disease, neutrophil engraftment failure, delayed platelet engraftment, and potential lentiviral vector–mediated insertional oncogenesis requiring long-term monitoring. Hypersensitivity reactions and interference with polymerase chain reaction–based human immunodeficiency virus testing have also been reported.

The US Food and Drug Administration also granted a Rare Pediatric Disease Priority Review Voucher, a program intended to encourage the development of treatments for rare pediatric diseases.

Source: Rocket Pharmaceuticals