FDA Approves Kresladi, First Gene Therapy for Severe LAD-I

The U.S. Food and Drug Administration (FDA) has approved Kresladi, the first gene therapy for severe leukocyte adhesion deficiency-I (LAD-I). This rare genetic immune disorder affects approximately one in one million children worldwide and often leads to early mortality. The approval follows a clinical trial at UCLA where all nine children treated with the therapy saw their immune function restored. LAD-I is caused by mutations in the ITGB2 gene, which disrupt the production of two proteins, CD11 and CD18. These proteins are necessary for white blood cells to reach and respond to infections. Without them, children face a high risk of life-threatening bacterial and fungal infections, making medical intervention vital for survival.

The clinical trial was a collaboration between Rocket Pharmaceuticals and UCLA investigators led by Dr. Donald Kohn. Because the condition is so rare, the trial enrolled nine patients ranging in age from 5 months to 9 years. Six patients received treatment at UCLA, while three others were treated in London and Spain. The therapy uses a one-time procedure to add a healthy copy of the ITGB2 gene to a child’s blood stem cells. Once these modified cells are returned to the patient, the body can produce functional immune cells, improving the child's ability to fight off illness.

Kresladi has shown promising results in terms of both safety and efficacy. All nine trial participants survived without the need for bone marrow transplants, and there were no reports of graft failure or immune rejection. This therapy was associated with fewer toxicities than traditional bone marrow transplantation, which typically requires intensive chemotherapy and immunosuppressive drugs. The trial results showed a significant reduction in infections that required hospitalization. Researchers also noted consistent improvements in the children's leukocytosis and an increase in the proteins essential for immune function.

For Dr. Kohn, who has worked on gene therapies for over three decades, this FDA approval is a landmark achievement. Kresladi was developed by Rocket Pharmaceuticals and is expected to be available at specialized treatment centers equipped for ex vivo gene therapy. The approval is also a significant result for the California Institute for Regenerative Medicine, which co-funded the clinical trials. Dr. Kohn hopes this milestone will encourage more investment in treatments for rare diseases as he continues to conduct trials for other severe immune disorders, demonstrating the capacity for gene therapy to change lives.