FDA
FDA greenlights Kresladi for severe leukocyte adhesion deficiency type I (LAD-I)
Brand name: Kresladi
Generic name: marnetegragene autotemcel
Manufacturer: Rocket Pharmaceuticals, Inc.
Approval date: March 26, 2026
Kresladi (marnetegragene autotemcel) is approved for the treatment of pediatric patients with severe leukocyte adhesion deficiency I (LAD-I) due to biallelic variants in ITGB2 without an available human leukocyte antigen (HLA)-matched sibling donor for allogeneic hematopoietic stem cell transplant.
Severe LAD-I is a rare, inherited immune deficiency caused by mutations in the ITGB2 gene, which prevent leukocytes from effectively fighting infections. Kresladi is an autologous hematopoietic stem cell (HSC)-based gene therapy that adds functional copies of the ITGB2 gene into the patient's HSCs. Apheresis is used to collect HSCs, then the autologous cells are enriched for CD34+ cells and transduced ex vivo with a vector encoding for the CD18 β-subunit of human β2 integrins (ITGB2). After Kresladi infusion, transduced CD34+ HSCs engraft in the bone marrow and differentiate into various cell types, including leukocytes capable of expressing functional CD18 protein. Functional CD18 protein enables formation of the CD18/CD11a heterodimer (Leukocyte Function-Associated Antigen-1, LFA-1) which facilitates leukocyte adhesion to endothelial surfaces and extravasation to infectious and inflammatory sites.
"As a clinician, I have seen firsthand the serious impact that severe LAD-I can have on young children and their families," investigator Donald Kohn, MD of the University of California Los Angeles, said in a press release from the manufacturer. "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."
Efficacy
Kresladi was granted accelerated approval based on surrogate endpoints: increase in neutrophil CD18 and CD11a surface expression at month 12 and sustained expression through month 24 post-infusion. Continued approval is contingent upon verification and description of clinical benefit in an ongoing clinical study and through a post-marketing registry.
Approval was supported by an open-label, single-arm, multicenter study in 9 pediatric patients with molecularly confirmed ITGB2-associated severe LAD-I. Severe LAD-I was defined as having neutrophil CD18 expression <2% or CD11a and/or CD11b expression <2% (if neutrophil CD18 expression ≥2%), documented biallelic ITGB2 mutations, and clinical history consistent with severe LAD-I or a known family history. All participants received Kresladi via IV infusion.
Of the 9 patients enrolled, 7 patients had baseline neutrophil CD18 expression <2% and thus were eligible for post-treatment CD18 assessment. After Kresladi infusion, CD18 expression increased in all 7 patients with median CD18 surface expression at month 12 and month 24 post-infusion of 54% (range, 20-87%) and 50% (range, 16-82%), respectively. Neutrophil CD18 expression was sustained through at least month 42 post-infusion in all 7 patients.
Neutrophil CD11a surface expression increased after Kresladi infusion in all 9 patients. Median CD11a surface expression at month 12 and month 24 post-infusion were 45% (range, 18-75%) and 39% (range, 17-65%), respectively. Neutrophil CD11a surface expression was sustained through at least month 42 post-infusion in all 9 patients.
None of the 9 patients received allogeneic hematopoietic stem cell transplant after Kresladi treatment. The median duration of follow-up after Kresladi infusion was 4.2 years (range, 3.6-5.7 years).
Safety
According to the Kresladi prescribing information, the most common adverse reactions (≥ 30%) are mucositis, upper respiratory tract infection, viral infection, febrile neutropenia, skin lesion, nausea/vomiting, rash/dermatitis, pyrexia, device related infection, and skin infection; decreased hemoglobin, decreased platelet count, decreased neutrophil count, decreased leukocyte count, and increased ALT and AST.
The label also includes warnings regarding serious infections, veno-occlusive disease, neutrophil engraftment failure, delayed platelet engraftment, LVV-mediated insertional oncogenesis, and hypersensitivity reactions.
Source: FDA News Release. (2026, March 26). FDA Approves First Gene Therapy for Severe Leukocyte Adhesion Deficiency Type I