Kresladi: the first FDA-approved gene therapy for Severe Leukocyte Adhesion Deficiency Type I
The FDA’s approval of Kresladi (marnetegragene autoemcel) marks a major milestone for pediatric patients with severe Leukocyte Adhesion Deficiency Type I (LAD-I), a rare immune disorder that affects 1 in 1 million people each year. It is the first FDA-approved gene therapy for this condition.
LAD-I is an inherited, life-threatening immune deficiency disorder caused by mutations in the ITGB2 gene, resulting in defective or deficient CD18 (also known as the beta-2 integrin subunit), a key component of leukocyte adhesion molecules. These molecules allow white blood cells to stick to blood vessel walls and travel to sites of infection. Without functional CD18, patients with severe LAD-I cannot effectively fight bacteria and other pathogens. They experience recurrent infections and face a grim prognosis, with approximately 75% dying by 2 years of age. Historically, the only curative option has been allogeneic hematopoietic stem cell transplantation, with success largely dependent on the availability of a suitable human leukocyte antigen (HLA)-matched sibling donor.
On March 26, 2026, the FDA approved Kresladi for treatment of pediatric patients with severe LAD-I who do not have an available HLA-matched sibling donor for stem cell transplantation.
This newly approved therapy is manufactured from the patient’s own cells, which are collected by apheresis. The autologous collection is then enriched for stem cells, and a lentiviral vector is introduced to deliver working copies of the ITGB2 gene, enabling expression of functional CD18. Before infusion, the patient undergoes a conditioning regimen to support engraftment of the corrected cells.
After a one-time infusion, the corrected cells begin producing normal CD18. This newly made CD18 pairs with the patient’s native CD11a protein to form stable leukocyte adhesion molecules, restoring the ability of white blood cells to adhere to blood vessel walls and reach sites of infection and inflammation. By addressing the underlying genetic defect, this targeted therapy offers the potential for a dramatically improved prognosis for affected children.
Resources:
FDA approves first gene therapy for severe leukocyte adhesion deficiency type I. News release. US Food and Drug Administration; March 26, 2026. Accessed March 30, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-severe-leukocyte-adhesion-deficiency-type-i
Justiz Vaillant AA, Ahmad F. Leukocyte Adhesion Deficiency. In: StatPearls [Internet]. StatPearls Publishing; 2026. Updated July 3, 2023. Accessed March 30, 2026. https://www.ncbi.nlm.nih.gov/books/NBK539770/
Kresladi [package insert]. Rocket Pharmaceuticals, Inc; 2026. Accessed March 30, 2026. https://www.fda.gov/media/191722/download?attachment