Kresladi

Kresladi (marnetegragene autotemcel) is a one-time gene therapy for the treatment of severe leukocyte adhesion deficiency-I (LAD-I) in children. LAD-I is an ultra-rare genetic immune disorder that prevents white blood cells from fighting infections, often leading to fatal outcomes in early childhood without a bone marrow transplant.

LAD-1 is caused by mutations in the ITGB2 gene, resulting in a lack or severe reduction of CD18, a key protein on the surface of white blood cells that helps them stick to blood vessel walls, move into tissues, and fight infections.

Kresladi works by delivering a functional copy of the ITGB2 gene into a patient’s own stem cells, allowing the body to produce CD18, a protein essential for normal immune function.

Kresladi is an autologous hematopoietic stem cell-based gene therapy FDA-approved for pediatric patients with severe leukocyte adhesion deficiency-I (LAD-I) due to biallelic variants in ITGB2 without an available human leukocyte antigen (HLA)-matched sibling donor for allogeneic hematopoietic stem cell transplant.

Kresladi received accelerated approval on March 26, 2026, based on increased neutrophil CD18 and CD11a surface expression, with continued approval dependent on positive clinical benefit in follow-up study data.

Pregnancy

Kresladi can cause fetal harm when administered to a pregnant woman. Kresladi must not be administered during pregnancy because of the risk associated with conditioning.

A negative serum pregnancy test must be confirmed before the start of mobilization and reconfirmed before conditioning procedures and before administration of Kresladi in females of childbearing potential.

Planning a future pregnancy. There are insufficient exposure data to provide a precise recommendation on the duration of contraception following treatment with Kresladi. Consult the Prescribing Information of the mobilization and conditioning agents for information on the need for effective contraception.

Infertility. There is no data available on the effects of Kresladi on fertility. Data is available on the risk of infertility with myeloablative conditioning. Advise patients of the option to cryopreserve semen or ova before treatment, if appropriate.

Breastfeeding

Tell your healthcare provider if you are breastfeeding or planning to breastfeed. There is no available data regarding the presence of Kresladi in human milk, the effect on the breastfed infant, and the effects on milk production.

Discontinue breastfeeding during myeloablative conditioning due to the potential risks.

The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Kresladi and any potential adverse effects on the breastfed child from Kreslai or from the underlying maternal condition.

Kresladi was studied in a small clinical trial of 9 children with severe LAD-I caused by ITGB2 gene changes. The study was open-label, single-arm, and multicenter, which means all patients received Kresladi and there was no comparison group (RP-L201- 0318; NCT03812263).

The study assessed whether treatment increased CD18 and CD11a levels on neutrophils, two proteins that help white blood cells function properly.

Study results

• In the 7 patients who had very low CD18 levels before treatment, all 7 showed increased CD18 expression after Kresladi.
• Median CD18 expression was 54% at Month 12 and 50% at Month 24.
• CD18 expression remained detectable through at least Month 42 in all 7 evaluable patients.
• All 9 patients showed increased CD11a expression after treatment.
• Median CD11a expression was 45% at Month 12 and 39% at Month 24.
• CD11a expression was sustained through at least Month 42 in all 9 patients.

Kresladi increased CD18 and CD11a, key white blood cell surface proteins linked to improved immune function, and those increases were maintained over time. These biomarker improvements supported the drug’s accelerated approval.

The most common side effects of Kresladi include mouth sores, cold-like infections, viral infections, fever, fever with low white blood cell counts, nausea, vomiting, rash, skin problems, skin infections, and infections related to a medical device such as a catheter or central line.

Blood tests may also show low red blood cells, low platelets, low neutrophils, low white blood cells, and increased liver enzymes.

This is not a complete list of side effects, and others may occur.

Tell your doctor or treatment team right away if you notice any side effects after treatment. You may also report side effects to Rocket Pharmaceuticals at 1-800-982-2410 or to the FDA at 1-800-FDA-1088

Serious Infections

Serious infections have occurred with Kresladi administration, which may be due the administration of myeloablative conditioning before Kresladi infusion.

Monitor patients for signs and symptoms of infection before and after Kresladi infusion and treat appropriately. Administer prophylactic antimicrobials according to institutional guidelines.

Avoid administration of Kresladi in patients with active bloodstream infections or other serious, untreated infections.

Any blood products required after Kresladi infusion should be irradiated.

Veno-Occlusive Disease

Veno-occlusive disease has occurred with Kresladi treatment. Increased susceptibility to veno-occlusive disease may occur due to the administration of myeloablative conditioning prior to Kresladi infusion. Monitor patients for signs and symptoms of veno-occlusive disease, including assessment of liver function tests during the first month following Kresladi infusion.

Neutrophil Engraftment Failure

Neutrophil engraftment failure may occur after treatment with Kresladi. Neutrophil engraftment failure is defined as failure to achieve three consecutive absolute neutrophil counts (ANC) ≥ 500 cells/microliter obtained on different days by Day 43 after infusion of Kresladi. Monitor neutrophil counts until engraftment has been achieved. If neutrophil engraftment failure occurs in a patient treated with Kresladi, provide rescue treatment with the back-up collection of CD34+ cells.

Delayed Platelet Engraftment

Delayed platelet engraftment may occur after treatment with Kresladi. Monitor platelet counts and bleeding until platelet engraftment and platelet recovery are achieved.

LVV-Mediated Insertional Oncogenesis

Lentiviral vector (LVV)-mediated insertional oncogenesis may occur after treatment with Kresladi. Hematologic malignancy is a lifelong risk and patients treated with Kresladi may develop hematologic malignancy at any time following treatment.

Monitor for hematologic malignancies clinically, and with a complete blood count (with differential) at least annually and integration site analysis as warranted for at least 15 years after treatment with Kresladi and as clinically indicated. If malignancy is detected in any patient who received Kresladi, contact Rocket Pharmaceuticals, Inc. at 1-800-982-2410 for reporting and to obtain instructions on collection of samples for testing.

Hypersensitivity Reactions

Hypersensitivity reactions, including anaphylaxis, may occur with the infusion of Kresladi. The dimethyl sulfoxide (DMSO) in Kresladi may cause hypersensitivity reactions, which may occur in patients with and without prior exposure to DMSO.

Monitor patients for signs and symptoms of hypersensitivity reactions during and after Kresladi infusion. If a hypersensitivity reaction occurs, pause infusion if ongoing and manage according to clinical practice.

Anti-Retroviral Use

Anti-retroviral medications may interfere with the manufacturing of Kresladi. If a patient requires anti-retrovirals for HIV prophylaxis, mobilization and apheresis of CD34+ cells for Kresladi manufacturing should be delayed until HIV infection is adequately ruled out. Patients should not take anti-retroviral medications for at least one month prior to mobilization, or for the expected duration required for the elimination of the anti-retroviral medications, and until all cycles of apheresis are completed.

Interference with Serology Testing

Patients who have received Kresladi are likely to test positive by polymerase chain reaction (PCR) assays for HIV due to LVV provirus insertion, resulting in a false-positive test for HIV. Therefore, patients who have received Kresladi should not be screened for HIV infection using a PCR-based assay.

Blood, Organ, Tissue, and Cell Donation

Patients treated with Kresladi should not donate blood, organs, tissues, or cells for transplantation at any time in the future.

Kresladi treatment starts by collecting the patient’s blood stem cells through a process called apheresis. The cells are then genetically modified in a lab to add a working copy of the ITGB2 gene, after which the patient receives conditioning chemotherapy and the modified cells are given back as a one-time IV infusion. These cells then travel to the bone marrow, where they can grow and begin making white blood cells with the CD18 protein.

Kresladi treatment process:

• Stem Cell Collection (Apheresis): Hematopoietic stem cells (CD34+ cells) are collected from the patient's blood through a process called apheresis.
• Genetic Modification (Manufacturing): These cells are sent to a laboratory where a lentiviral (LV) vector is used to insert a functional ITGB2 gene into the cells' DNA.
• Conditioning: Before the modified cells are returned, the patient receives myeloablative conditioning (typically chemotherapy). This clears out the old, defective stem cells in the bone marrow to make room for the new ones.
• Reinfusion: The modified cells (now the Kresladi drug product) are administered back to the patient as a one-time intravenous (IV) infusion.
• Engraftment & Recovery: The new stem cells migrate to the bone marrow and begin producing healthy white blood cells that express the CD18 protein. Patients are monitored for engraftment (the successful growth of new cells), which typically occurs within several weeks.

The recommended minimum Kresladi dose is 2.8 × 106 CD34+ cells/kg as a single intravenous infusion. The dose is calculated based on the patient’s weight before the first apheresis.

The time for infusion will vary, but will usually be less than 10 minutes.

If two infusion bags are provided, administer the contents of the first infusion bag completely before proceeding to thaw and infuse the contents of the second infusion bag. Wait 1 to 2 hours after administration of the first bag before thawing and infusion of the second bag.

Tell your healthcare provider about all medications you take, including prescription and over-the-counter medicines, vitamins, and herbal products.

Anti-retrovirals: Patients should not take anti-retroviral medications for one month before mobilization, or for the expected duration required for elimination of the anti-retroviral medications, and until all cycles of apheresis are completed

Live Vaccines: The safety and effectiveness of immunization with live viral vaccines during or following Kresladi treatment have not been studied. Vaccination is not recommended during the 6 weeks preceding the start of myeloablative conditioning, and until hematological recovery following treatment with Kresladi. Where feasible, administer childhood vaccinations before myeloablative conditioning for this treatment.

Not all possible drug interactions are listed here

Manufacturing failure. Kresladi is made from the patient’s own stem cells, but in some cases, the treatment cannot be successfully manufactured. If that happens, another stem cell collection and another round of manufacturing may be needed.

Rocket Pharmaceuticals, Inc. 9 Cedarbrook Drive Cranbury, NJ 08512