The US Food and Drug Administration (FDA) has granted accelerated approval for Kresladi (marnetegragene autotemcel), an autologous haematopoietic stem cell-based gene therapy. 

It is indicated for the treatment of paediatric patients with severe leukocyte adhesion deficiency-I (LAD-I) due to biallelic variants in ITGB2 without an available human leukocyte antigen-matched sibling donor for allogeneic haematopoietic stem cell transplant.  

This indication is approved under accelerated approval based on increase in neutrophil CD18 and CD11a surface expression.  

Rocket Pharmaceuticals and the regulator have agreed that confirmation of clinical benefit will be based on the evaluation of longer-term follow-up data of treated patients in the ongoing clinical study and through a post-marketing registry. 

The FDA also granted Rocket a Rare Pediatric Disease Priority Review Voucher (PRV), a programme designed to encourage development of therapies for rare paediatric diseases. 

“The approval of Kresladi represents an important milestone for the severe LAD-I community,” said Gaurav Shah, Chief Executive Officer, Rocket Pharmaceuticals. “This approval reflects the dedication of patients, families, investigators, and regulators who have worked together to advance research of this ultra-rare disease. We look forward to making Kresladi available to eligible patients in the United States.” 

What is leukocyte adhesion deficiency-I? 

LAD-I is an ultra-rare genetic paediatric disease caused by mutations in the ITGB2 gene encoding for CD18, a key protein that is expressed along CD11 integrins to facilitate leukocyte adhesion to the blood vessel wall and migration to tissues to confine and clear infections and orchestrate wound repair.  

Patients with severe LAD-I typically show very diminished CD11a expression. Infants with severe LAD-I suffer from recurrent, life-threatening bacterial, and fungal infections that respond poorly to antimicrobials and require frequent hospitalisations.  

In the US, the incidence of LAD-I is estimated to range from approximately one in 100,000 to one in 200,000 live births, with roughly two-thirds of affected patients classified as having the severe form of the disease. 

“As a clinician, I have seen firsthand the serious impact that severe LAD-I can have on young children and their families,” said Dr Donald Kohn, Principal Investigator of the Phase I/II study and Distinguished Professor of Microbiology, Immunology & Molecular Genetics at the University of California, Los Angeles (UCLA). “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.”