Clinical Report: FDA Approves Gene Therapy for Severe Pediatric LAD-I

Overview

The FDA has granted accelerated approval for marnetegragene autotemcel (KRESLADI) for pediatric patients with severe leukocyte adhesion deficiency-I due to biallelic ITGB2 variants who do not have a matched sibling donor for hematopoietic stem cell transplant, addressing a critical need in this rare genetic immunodeficiency.

Background

Severe leukocyte adhesion deficiency type I (LAD-I) is a rare genetic disorder caused by mutations in the ITGB2 gene, leading to severe immunodeficiency and high mortality in untreated cases during early childhood. The condition results in recurrent infections and significant healthcare burden. The approval of KRESLADI represents a significant advancement in treatment options for affected pediatric patients who lack suitable donors for traditional stem cell transplants.

Data Highlights

No numerical data available in the source material.

Key Findings

• KRESLADI is approved for pediatric patients with severe LAD-I due to biallelic ITGB2 variants.
• Approval is based on increased neutrophil CD18 and CD11a surface expression.
• Continued approval is contingent on long-term follow-up and a postmarketing registry.
• The safety profile includes risks such as serious infections, potential oncogenesis, and complications from myeloablative conditioning.
• The estimated incidence of severe LAD-I in the US is 1 in 100,000 to 1 in 200,000 live births.

Clinical Implications

Healthcare providers should consider KRESLADI as a treatment option for pediatric patients with severe LAD-I who lack a matched sibling donor. Ongoing monitoring for potential adverse effects, including serious infections and long-term outcomes, is essential following gene therapy administration.

Conclusion

The approval of KRESLADI marks a pivotal moment in the management of severe LAD-I, providing a new therapeutic avenue for patients who previously had limited options. Continued research and monitoring will be crucial to establish the long-term efficacy and safety of this gene therapy.

References

1. United States Department of Health and Human Services, WTAS, 2026 -- FDA Approves First-Ever Gene Therapy for Treatment of Genetic Hearing Loss Under National Priority Voucher Program
2. Ophthalmology Management, 2025 -- Efficacy Data on MeiraGTXs Gene Therapy for Children with AIPL1 Associated Severe Retinal Dystrophy Published in Lancet
3. Retinal Physician, 2025 -- FDA Grants RMAT Status to Gene Therapy
4. FDA, 2026 -- FDA Approves First Gene Therapy for Severe Leukocyte Adhesion Deficiency Type I
5. EBMT/ESID, 2021 -- EBMT/ESID inborn errors working party guidelines for hematopoietic stem cell transplantation for inborn errors of immunity
6. conexiant — FDA Grants Accelerated Approval for OTOF Gene Therapy
7. EBMT/ESID inborn errors working party guidelines for hematopoietic stem cell transplantation for inborn errors of immunity - PMC
8. FDA Approves First Gene Therapy for Severe Leukocyte Adhesion Deficiency Type I | FDA
9. March 26, 2026 Summary Basis for Regulatory Action - KRESLADI