FDA Approval of Kresladi Expands Gene Therapy in Pediatric Rare Diseases

FDA’s March 2026 approval of marnetegragene autotemcel (brand name Kresladi) for treating severe leukocyte adhesion deficiency type I (LAD-I) signifies an inflection point for rare disease gene therapy and reinforces how regulatory flexibility and surrogate endpoints are accelerating the path to market for ultra-rare pediatric conditions.¹ The decision highlights movement in the cell and gene therapy landscape toward earlier intervention and scalable development strategies in diseases with high unmet need.²

Developed by Cranbury, NJ-based Rocket Pharmaceuticals, marnetegragene autotemcel is the first gene therapy approved for LAD-I, a rare inherited immune disorder caused by mutations in the ITGB2 gene. The condition prevents white blood cells from effectively combating infections, leading to recurrent, life-threatening bacterial and fungal infections, often beginning in early childhood.³

The therapy is indicated for pediatric patients with severe LAD-I who lack a human leukocyte antigen-matched sibling donor for allogeneic hematopoietic stem cell transplant, which has historically been the only potentially curative option. Transplantation carries significant risks, including high morbidity and mortality, particularly in patients without suitable donors.¹

How does this gene therapy address the underlying biology of LAD-I?

The gene therapy uses a patient’s own hematopoietic stem cells, which are genetically modified to introduce functional copies of the ITGB2 gene, according to FDA. Following conditioning, a single intravenous infusion is administered to restore expression of CD18 and CD11a proteins on the surface of white blood cells, enabling improved immune function.

This autologous approach is designed to directly correct the genetic defect driving disease pathology, offering the potential for durable benefit after a one-time treatment. By restoring the function of key adhesion molecules required for immune cell trafficking, the therapy targets the root cause of immune dysfunction rather than managing downstream complications.

“[The] accelerated approval provides a breakthrough treatment for pediatric patients with severe leukocyte adhesion deficiency type I—the first FDA-approved gene therapy to treat this disease,” said Vinay Prasad, MD, chief medical and scientific officer and director of FDA’s Center for Biologics Evaluation and Research (CBER).

What clinical evidence supported accelerated approval?

The approval was based on data from a single-arm, open-label, multicenter study evaluating biomarker-driven endpoints. Patients treated with marnetegragene autotemcel demonstrated increased expression of CD18 and CD11a on neutrophils at 12 months, with sustained effects through 24 months.¹ These biomarkers are considered indicative of improved immune activity and were used as surrogate endpoints reasonably likely to predict clinical benefit.

Why is this approval important for the gene therapy landscape?

Marnetegragene autotemcel’s approval reflects a convergence of scientific innovation and regulatory adaptation that impacts the gene therapy field. The therapy received multiple expedited designations, including orphan drug, rare pediatric disease, regenerative medicine advanced therapy, and fast track, which highlight FDA’s willingness to accelerate development in high-need indications, the agency stated in a press release.¹

More broadly, the decision signals growing confidence in autologous gene therapies targeting hematologic and immunologic disorders. It also reinforces the role of surrogate endpoints and smaller, focused clinical datasets in enabling earlier access to transformative therapies.

References

1. FDA. FDA Approves First Gene Therapy for Severe Leukocyte Adhesion Deficiency Type I. Published 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
2. Barrett D, Cannon PM, Mingozzi F, Porteus M, Rivière I, Flotte TR. Overcoming barriers to commercially pre-viable gene and cell therapies for rare and ultra-rare diseases. Mol. Ther. 2025;33(11):5316-5326. doi: 10.1016/j.ymthe.2025.09.049
3. Novoa EA, Kasbekar S, Thrasher AJ, et al. Leukocyte adhesion deficiency-I: A comprehensive review of all published cases. J. Allergy Clin. Immunol.:Pract. 2018;6(4):1418-1420.e10. doi: 10.1016/j.jaip.2017.12.008