FDA Approves Marne-Cel, First Stem Cell-Based Gene Therapy for Pediatric Patients With LAD-I

The FDA approved marnetegragene autotemcel (marne-cel, Kresladi; Rocket Pharmaceuticals) the treatment of severe leukocyte adhesion deficiency type I (LAD-I). This approval, for pediatric patients with LAD-I due to biallelic variants in ITGB2 without an available human leukocyte antigen (HLA)-matched sibling donor for allogeneic hematopoietic stem cell transplant (HSCT), marks the first gene therapy for the treatment of this disease.^1,2

“The approval of [marne-cel] represents an important milestone for the severe LAD-I community,” Gaurav Shah, MD, CEO of Rocket Pharmaceuticals, said in a news release. “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 [marne-cel] available to eligible patients in the United States.”²

Severe LAD-I is a rare, inherited immune deficiency that is caused by mutations in the ITGB2 gene, which prevent white blood cells from effectively fighting infections. Patients who have severe LAD-I experience recurrent, life-threatening bacterial and fungal infections with substantial morbidity and mortality in their first decade of life. Allogeneic HSCT is considered in some patients; however, it is associated with significant morbidity and mortality, especially for those who do not have an HLA-matched sibling donor.¹

Marne-cel consists of the patient’s own hematopoietic stem cells, which are genetically modified to introduce functional copies of the ITGB2 gene. Following conditioning, a single dose of the gene therapy is infused intravenously, and it restores CD18 and CD11a cell surface expression in white blood cells, including neutrophils.¹

The safety and effectiveness of marne-cel were established in an open-label, single-arm, multicenter phase 1/2 clinical trial (NCT03812263)³. These findings, which were published in the New England Journal of Medicine, evaluated the outcomes of 9 children with LAD-I who were treated with marne-cel. Of note, none of the 9 patients had graft failure. HSCT-free survival was 100% (95% CI, 66–100) at 1 year after infusion (P < .001). All of the patients who were enrolled at younger than 1 year of age were alive beyond 2 years of age. Pretreatment neutrophilia and skin abnormalities related to LAD-I resolved.^3,4

Further, the annualized incidence of infection-related hospitalizations beyond 90 days after engraftment through 24 months following marne-cel infusion was approximately 74.45% lower than the incidence prior to marne-cel infusion. In addition, the annualized incidence of prolonged infection-related hospitalizations was 81.95% lower, and the annualized incidence of prespecified serious infections was 84.90% lower.⁴

The data indicated that serious adverse events (AEs) related to myeloablative busulfan conditioning were observed, and no AEs attributed to gene therapy were reported.⁴ The most common AEs identified during the trial included anemia, low platelet and white blood cell counts, mouth sores, upper respiratory infections, viral infections, fever, febrile neutropenia, nausea, vomiting, skin infection, rash, vascular device-related infection, and increased liver enzymes.¹

“The approval of [marne-cel] represents a significant development for individuals affected by severe LAD-I and the broader primary immunodeficiency community,” said Vanessa Tenembaum, CEO of the Jeffrey Modell Foundation, in the news release. “For families impacted by this rare and serious disease, this approval underscores the importance of continued efforts to improve outcomes for patients with primary immunodeficiencies.”²

REFERENCES

1. FDA Approves First Gene Therapy for Severe Leukocyte Adhesion Deficiency Type I. FDA. News release. March 26, 2026. Accessed March 27, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-severe-leukocyte-adhesion-deficiency-type-i

2. Rocket Pharmaceuticals Announces FDA Approval of KRESLADI™ for Pediatric Patients with Severe Leukocyte Adhesion Deficiency-I (LAD-I). Businesswire. News release. March 27, 2026. Accessed March 27, 2026. https://www.businesswire.com/news/home/20260326279809/en/Rocket-Pharmaceuticals-Announces-FDA-Approval-of-KRESLADI-for-Pediatric-Patients-with-Severe-Leukocyte-Adhesion-Deficiency-I-LAD-I

3. A Clinical Trial to Evaluate the Safety and Efficacy of RP-L201 in Subjects With Leukocyte Adhesion Deficiency-I. ClinicalTrials.gov identifier: NCT03812263. Updated November 15, 2023. Accessed March 27, 2026. https://clinicaltrials.gov/study/NCT03812263

4. Booth C, Sevilla J, Almarza E, et al. Lentiviral Gene Therapy for Severe Leukocyte Adhesion Deficiency Type 1. New J Engl Med. 2025;392(17):1698-1709. doi:10.1056/NEJMoa2407376