What Is Kresladi, and Why Does It Matter?
Kresladi (marnetegragene autotemcel) is a gene therapy approved by the FDA to treat a rare and serious immune condition called leukocyte adhesion deficiency type I (LAD-I). It is used for children with severe forms of this genetic disease caused by changes in the ITGB2 gene inherited from both parents (biallelic), especially when they do not have a closely matched sibling donor for a stem cell transplant.
Severe LAD-I makes it hard for white blood cells to fight infections. Children with this condition often have repeated, serious bacterial and fungal infections that can be life threatening, especially in early life. A stem cell transplant from a donor may be an option for some patients, but it can have health risks, particularly when a closely matched sibling donor is not available.
Kresladi gene therapy is made from the patient’s own blood-forming stem cells. In the lab, a working copy of the ITGB2 gene is added to these cells. After pretreatment to prepare your body, you receive a single intravenous (IV) infusion. The goal is to restore two proteins on white blood cells, namely CD18 and CD11a, to help your immune system fight infections better.
Kresladi uses your child’s stem cells, which are collected in advance and changed outside the body before being given back. This approach aims to fix the underlying cause of the disease rather than only managing infections.
This accelerated approval is important as it is the first gene therapy for LAD-I in the U.S. for children with severe LAD-I and their families. It offers the hope of fewer infections, more opportunities to take part in daily activities, and an improved quality of life.
Why Was It Approved?
Kresladi received accelerated approval after it was shown to be safe and effective in children with severe LAD-I in a clinical trial.
In that study, nine children with severe LAD-I were treated with Kresladi. After treatment, the biomarkers CD18 and CD11a on white blood cells increased by month 12 and stayed higher through month 24, indicating the immune cells were working better. The FDA accepted these markers as an indirect (surrogate) endpoint that is reasonably likely to predict clinical benefit in LAD-I.
The most common side effects were low red blood cells, low platelets, and low white blood cells; mouth sores; upper respiratory and viral infections; fever; nausea and vomiting; skin infections and rash; infections related to vascular devices; and higher liver enzymes.
Because this decision used the FDA’s accelerated approval pathway and relied on a surrogate measure rather than direct clinical outcomes, confirmatory studies are required to verify and describe benefit. The results of those studies will guide continued approval.
What Do I Need to Know?
Kresladi is given one time by IV after full myeloablative conditioning, which is a pretreatment to prepare your or your child’s body. It is for use with the patient’s own cells only (autologous use). Patients receive the infusion soon after conditioning is complete.
Because the risk of infection is higher around the time of treatment, you or your child’s health care provider will closely watch for fever, mouth sores, cough, or other signs of infection and treat them as needed.
After treatment with Kresladi, your or your child’s white blood cell count will be low for a while until the transplanted cells attach and start working properly (engraftment).
Some children may develop a serious liver problem called veno-occlusive disease, white blood cells may take longer to recover (engraftment failure), and platelets may return slowly. There is also a long-term risk of blood cancers from the gene therapy process. You or your child will need regular blood tests and long-term follow-up to monitor their health.
Before you or your child receives Kresladi, do not use medicines for viral infections for at least a month before stem cell collection and until all collection cycles are complete, as these medicines can interfere with the therapy’s manufacturing.
Live vaccines have not been studied with this treatment. Avoid vaccinations from six weeks before Kresladi treatment until recovery. Childhood vaccines should be given before the conditioning process when possible.
Kresladi should not be used during pregnancy because its treatment process carries serious risks to both mother and baby. Breastfeeding should also be stopped during treatment, as it’s not known whether the therapy passes into breast milk or could harm the infant.
After therapy, some blood tests may show a false-positive result for HIV, so always tell your health care provider before any testing. You or your child should never donate blood, organs, tissues, or cells in the future.
Kresladi is expected to become commercially available by the end of 2026.