Kresladi (marnetegragene autotemcel): FDA approval, pivotal trial and safety
Approved
Type
Gene therapy · Intravenous
FDA-approved use
To treat 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 transplantWording from FDA's list of novel approvals.
Company
Rocket
Application
BLA 125806
Specialty
Hematology, Genetics
At a glance
Kresladi (marnetegragene autotemcel) is an autologous stem cell gene therapy approved under accelerated approval for pediatric patients with severe LAD-I due to biallelic ITGB2 variants who lack an HLA-matched sibling donor. In the pivotal single-arm study of 9 children, HSCT-free survival was 100% at 1 year (95% CI 66 to 100; P<0.001). Serious infections and effects of myeloablative conditioning were the main safety concerns.
What it is and how it works
Kresladi adds working copies of the ITGB2 gene to a patient's own CD34+ stem cells using a lentiviral vector. The modified cells engraft and produce leukocytes that express functional CD18, which allows leukocytes to adhere to vessel walls and move into infected or inflamed tissue. Unlike allogeneic transplant, it uses the patient's own cells, so it needs no donor and carries no graft-versus-host disease risk from a donor graft.
Open-label, single-arm, multinational phase 1-2 study with 24 months of follow-up. Patients then enrolled in a long-term follow-up study.
Patients
9 children with severe LAD-I
Compared with
None. The primary end point was tested against a null hypothesis of 39% survival.
Primary endpoint
Survival without allogeneic HSCT at least 1 year after infusion, and at 2 years of age for those younger than 1 year at enrollment.
Result
HSCT-free survival was 100% (95% CI 66 to 100) at 1 year (P<0.001). All patients enrolled before age 1 year were alive beyond 2 years of age.
Other results
Pretreatment neutrophilia and LAD-I skin abnormalities resolved. Annualized infection-related hospitalizations were 74.45% lower than before treatment, prolonged infection-related hospitalizations 81.95% lower, and prespecified serious infections 84.90% lower.
Safety in the trial
Serious adverse events related to busulfan conditioning occurred. No adverse events were attributed to the gene therapy, and no patient had graft failure. The label reports serious adverse reactions in 4 of 9 patients (44%).
How does Kresladi (marnetegragene autotemcel) compare with the alternatives (Allogeneic HSCT (matched donor), Antimicrobial prophylaxis and treatment, Granulocyte transfusions) for 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 t…? Summarize head-to-head and indirect evidence, efficacy, safety and where each fits, with citations.
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Safety signals
There is no boxed warning. Warnings cover serious infections, veno-occlusive disease, neutrophil engraftment failure, delayed platelet engraftment, hypersensitivity reactions, and the risk of insertional oncogenesis from the lentiviral vector. Patients need monitoring for hematologic malignancy at least annually for at least 15 years. Myeloablative conditioning drives much of the toxicity. Common adverse reactions included mucositis, upper respiratory tract infection, viral infection, febrile neutropenia, and cytopenias. Serious adverse reactions occurred in 4 of 9 patients (44%), including serious infections, pulmonary arterial hypertension, sensorineural deafness, and veno-occlusive disease. Irradiated blood products are required after infusion.
What it competes with
Allogeneic hematopoietic stem cell transplant from a matched donor is the established curative treatment for severe LAD-I. Until transplant, care centers on preventing and treating infections.
Allogeneic HSCT (matched donor)Curative, but limited by donor availability, graft-versus-host disease, and graft failure.
Antimicrobial prophylaxis and treatmentSupportive care that manages infections but does not correct the underlying defect.
Granulocyte transfusionsOccasionally used as a temporary supportive measure during severe infection.
Bottom line for clinicians
Kresladi is for children with severe LAD-I who have no HLA-matched sibling donor. Approval rests on a surrogate end point (neutrophil CD18 and CD11a expression), and the data come from a small single-arm study, so clinical benefit still needs confirmation. Weigh the toxicity of myeloablative conditioning and the need for long-term malignancy surveillance.
Dosing, contraindications and full warnings are in the prescribing information.
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Last updated October 28, 2026 by 2 Minute Medicine.
For healthcare professionals. A summary of public FDA documents and published trials, not medical advice. Check the full prescribing information before prescribing.
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