FDA Grants Accelerated Approval to Rocket’s Gene Therapy for LAD-1

Rare Daily Staff

The U.S. Food and Drug Administration has granted accelerated approval to Rocket Pharmaceuticals’ gene therapy to treat children with the most severe form of a rare inherited immune disorder that leaves them unable to fight off routine infections.

The Food and Drug Administration granted the approval to Kresladi for pediatric patients with severe leukocyte adhesion deficiency type 1, or LAD-1, who lack a matched sibling donor for a stem cell transplant. It is the first approved gene therapy to treat the condition.

LAD-1 is an ultra-rare, life-threatening genetic disease that appears in infancy. Children with the severe form lack sufficient levels of a protein called CD18, which works with partner molecules known as CD11 integrins to help infection-fighting white blood cells adhere to blood vessel walls and move into tissues. Without that adhesion step, white blood cells remain trapped in the bloodstream, leaving babies vulnerable to recurrent bacterial and fungal infections, poor wound healing, and a high risk of death in early childhood without effective treatment.

Kresladi is a one-time treatment made from a child’s own blood-forming stem cells that have been modified in a lab to add a working copy of the faulty ITGB2 gene. Doctors collect the patient’s stem cells, insert the healthy gene using a disabled lentiviral vector, then infuse the altered cells back after chemotherapy that clears space in the bone marrow. The goal is for the modified cells to engraft and rebuild the immune system so white blood cells can reach sites of infection and help heal wounds.

The FDA based its accelerated approval on laboratory evidence that the gene therapy restored the missing adhesion proteins, specifically increased levels of CD18 and CD11a on neutrophils, a type of white blood cell. Longer-term data from the ongoing clinical study, along with results from a postmarketing registry, will be needed to confirm that those changes translate into sustained clinical benefits, such as fewer serious infections and improved survival.

In addition to approving the therapy, the FDA granted Rocket a Rare Pediatric Disease Priority Review Voucher, a tradable credential intended to spur development of treatments for children with uncommon conditions. Rocket said it plans to evaluate options to sell the voucher, which could bring in significant nondilutive funding and bolster the company’s financial flexibility.

For families, the decision offers a new option beyond allogeneic stem cell transplant, which can cure the disease but relies on finding a well-matched donor and carries risks such as graft-versus-host disease, in which donor cells attack the recipient’s tissues. Kresladi is designed for children who do not have a human leukocyte antigen–matched sibling donor, a common barrier in this small and widely dispersed patient population.

Like other gene and cell therapies, Kresladi comes with significant safety considerations. Children must receive myeloablative conditioning chemotherapy before infusion, which temporarily wipes out their existing bone marrow and further increases their susceptibility to infections. The product label warns of serious infections, liver vein blockages known as veno-occlusive disease, failure of the modified cells to engraft, delayed platelet recovery, and a lifelong risk of blood cancers due to insertion of the viral vector into the genome.

“The approval of Kresladi represents a significant development for individuals affected by severe LAD-1 and the broader primary immunodeficiency community,” said Vanessa Tenembaum, CEO of the Jeffrey Modell Foundation, a global nonprofit organization dedicated to early diagnosis and treatment of primary immunodeficiency. “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.”