The US FDA has granted accelerated approval to KRESLADI (marnetegragene autotemcel), an autologous hematopoietic stem cell-based gene therapy developed by Rocket Pharmaceuticals for pediatric patients with severe leukocyte adhesion deficiency-I (LAD-I) caused by biallelic variants in the ITGB2 gene. The approval, announced on March 27, 2026, makes KRESLADI the first gene therapy cleared by the FDA for this ultra-rare primary immunodeficiency. The agency also granted Rocket a Rare Pediatric Disease Priority Review Voucher. LAD-I affects an estimated one in 100,000 to one in 200,000 live births in the US, with roughly two-thirds of cases classified as severe. Without treatment, infants with the severe form face recurrent life-threatening bacterial and fungal infections and high early-childhood mortality.
KRESLADI is indicated specifically for pediatric patients with severe LAD-I who lack an available human leukocyte antigen (HLA)-matched sibling donor for allogeneic hematopoietic stem cell transplant, the only previously established curative option. The approval was granted under the accelerated approval pathway, based on a surrogate endpoint: increases in neutrophil CD18 and CD11a surface expression following treatment. Continued approval may be contingent on verification of clinical benefit through longer-term follow-up of treated patients in the ongoing clinical study and through a post-marketing registry. The prescribing information carries warnings for serious infections, veno-occlusive disease, neutrophil engraftment failure, delayed platelet engraftment, lentiviral vector-mediated insertional oncogenesis requiring monitoring for at least 15 years, and hypersensitivity reactions.
The approval was supported by data from a Phase I/II clinical study led by Donald B. Kohn at the University of California, Los Angeles. The source material does not disclose specific patient numbers or quantitative efficacy data from the trial. The surrogate endpoint of restored CD18 and CD11a expression on neutrophils reflects the underlying biology of LAD-I, in which mutations in ITGB2 prevent production of functional CD18 protein, impairing leukocyte adhesion and migration to sites of infection. Research supporting KRESLADI's development was funded in part by the California Institute for Regenerative Medicine.
For the small population of children with severe LAD-I, the approval addresses a defined gap. Allogeneic hematopoietic stem cell transplant from an HLA-matched sibling donor has been the standard curative approach, but most patients lack such a donor. Without transplant, management has been limited to antimicrobial prophylaxis and treatment of acute infections, neither of which corrects the underlying immune defect. The development landscape for LAD-I remains narrow, consistent with the disease's rarity. A separate lentiviral gene therapy program using a distinct vector backbone (TYF-ITGB2) is in Phase I/II development at the Shenzhen Geno-Immune Medical Institute in China. Academic groups are also pursuing gene editing strategies, including CRISPR/Cas9-based correction of ITGB2 mutations at University College London and adenine base editing approaches at US academic institutions, though these remain in preclinical or early investigational stages. Separately, NIH-sponsored trials are evaluating haploidentical transplant protocols as an alternative for patients without matched sibling donors. The accelerated approval of KRESLADI establishes a regulatory precedent in this space, and the requirement for confirmatory long-term data will be closely watched given the lentiviral vector platform's associated risk of insertional oncogenesis, a concern that gene editing approaches aim to circumvent.
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