KRESLADI

KRESLADI is an FDA-registered drug product whose active ingredient is MARNETEGRAGENE AUTOTEMCEL. It is labelled by Rocket Pharmaceuticals, Inc. taken by intravenous and marketed as a cellular therapy product. Identifiers on file: NDC 83537-034, application BLA125806, label effective 20260701. This page reproduces the FDA-approved label text so you can check what a product is, who makes it and how it is supplied before discussing it with a pharmacist or prescriber.

Across FDA labelling, products containing MARNETEGRAGENE AUTOTEMCEL are most often described in connection with: hematopoietic stem, treatment pediatric, severe leukocyte, adhesion deficiency-i, lad-i due, biallelic variants, itgb without, available human. Wording differs between labels, and the full indications section on this page takes precedence when it is present.

1 INDICATIONS AND USAGE KRESLADI is indicated for the treatment of 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. This indication is approved under accelerated approval based on increase in neutrophil CD18 and CD11a surface expression [see Clinical Studies (14) ]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). KRESLADI is an autologous hematopoietic stem cell-based gene therapy indicated for the treatment of 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. ( 1 ) This indication is approved under accelerated approval based on increase in neutrophil CD18 and CD11a surface expression [see Clinical Studies (14) ] . Continued approval may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

2 DOSAGE AND ADMINISTRATION For autologous use only. For intravenous use only. Patients must undergo hematopoietic stem cell (HSC) mobilization followed by apheresis to obtain CD34+ cells for KRESLADI manufacturing. ( 2.2 ) Dosing of KRESLADI is based on the number of CD34+ cells in the infusion bag(s) per kg of body weight. ( 2.1 ) The minimum recommended dose is 2.8 × 10 6 CD34+ cells/kg. ( 2.1 ) Full myeloablative conditioning must be administered before infusion of KRESLADI. ( 2.2 ) Verify the patient's identity matches the unique patient identification information on the KRESLADI infusion bag(s) prior to infusion. ( 2.2 ) Do not sample, alter, or irradiate KRESLADI. ( 2.2 ) Do not use an in-line blood filter or infusion pump. ( 2.3 ) 2.1 Dose For autologous use only. For one-time single-dose intravenous use only. The recommended minimum dose of KRESLADI is a single intravenous infusion of 2.8 × 10 6 CD34+ cells/kg. The dose is calculated based on the patient's weight prior to first apheresis. See the Lot Information Sheet provided with the product shipment for additional information pertaining to dose. Up to two drug product lots may be administered to meet the minimum dose. 2.2 Preparation Before KRESLADI Infusion Before mobilization, apheresis, and conditioning are initiated, confirm that autologous hematopoietic stem cell (HSC) transplantation is appropriate for the patient. Consider administering ustekinumab prior to mobilization and apheresis and/or prior to KRESLADI infusion. Mobilization and Apheresis Administer granulocyte-colony-stimulating factor (G-CSF) and plerixafor for HSC mobilization followed by apheresis to obtain CD34+ cells for product manufacturing. Weigh the patient prior to the first apheresis collection. Collect a recommended target number of CD34+ cells of 20 × 10 6 CD34+ cells/kg. Repeat additional cycles of mobilization and apheresis after at least 14 days to obtain more cells for KRESLADI manufacture if the minimum dose of 2.8 × 10 6 CD34+ cells/kg is not met. Back-Up CD34+ Cell Collection Obtain and cryopreserve an additional collection of CD34+ cells of ≥ 2 × 10 6 CD34+ cells/kg at the treatment center prior to initiating myeloablative conditioning and infusion with KRESLADI. Administer the back-up collection for rescue treatment if there is: 1) compromise of KRESLADI after initiation of conditioning and before KRESLADI infusion, 2) primary engraftment failure, or 3) loss of engraftment after infusion with KRESLADI. Myeloablative Conditioning Do not begin conditioning until KRESLADI has been received and stored at the treatment center and the availability of the back-up collection of CD34+ cells is confirmed. Administer myeloablative conditioning before infusion of KRESLADI based on institutional guidelines. Consult the prescribing information for the conditioning agents prior to treatment. Infuse KRESLADI 24-48 hours after completion of myeloablative conditioning. Receipt and Storage of KRESLADI Ensure the availability of vapor phase of liquid nitrogen storage at less than or equal to -150°C (-238°F) at the treatment center. KRESLADI is shipped to the treatment center in the vapor phase of liquid nitrogen shipper. Confirm the patient's identity with the patient identifiers on the shipper and labels. If there are any concerns about the product or packaging upon receipt, contact Rocket Pharmaceuticals at 1-800-982-2410. Keep the infusion bag(s) in the metal cassette(s) and transfer KRESLADI from the vapor phase of liquid nitrogen shipper to the onsite vapor phase of liquid nitrogen storage (at ≤ -150°C (≤ -238°F) until ready for thaw and administration). Preparation of KRESLADI for infusion Confirm the infusion time in advance and adjust the start time of KRESLADI thaw such that it will be available for infusion when the patient and the healthcare provider are ready. Complete infusion of each bag of KRESLADI within 30 minutes of the start of thaw. 1. Confirm patient identity: Prior to KRESLADI preparation, match the patient's identity with the patient identifiers on the KRESLADI cassette(s). Do not remove the KRESLADI infusion bag from the cassette if the information on the patient-specific label does not match the intended patient and contact Rocket Pharmaceuticals at 1-800-982-2410. 2. Once patient identification is confirmed, remove the KRESLADI infusion bag(s) from the cassette(s) and check that the patient information on the cassette label(s) matches the bag label(s). 3. A KRESLADI dose may be contained in one or two patient-specific infusion bags. Two infusion bags could be from two different drug product lots. Verify the number of bags received for the indicated dose of KRESLADI. Use the accompanying Lot Information Sheet to confirm that each infusion bag is within the expiration date prior to preparation of KRESLADI for infusion. If two infusion bags have been received, thaw and administer each infusion bag one at a time. Wait 1 to 2 hours after administration of the first bag before thawing of the second KRESLADI bag. Maintain the second infusion bag, if applicable, within the vapor phase of liquid nitrogen storage to maintain temperature less than or equal to -150°C (-238°F) until time to thaw. 4. Inspect each infusion bag(s) for any breaches of integrity such as breaks or cracks before thawing. If the bag(s) is compromised, follow the local guidelines and call Rocket Pharmaceuticals at 1-800-982-2410. 5. Place the infusion bag inside a sterile plastic bag per local institutional guidelines. 6. Thaw KRESLADI at 37°C (98.6°F) in a water bath or dry-thaw method until there is no visible ice in the infusion bag. Thawing should take no longer than 5 minutes. Promptly remove the infusion bag once thawed and keep it at room temperature. • Do not leave KRESLADI unattended and do not submerge the infusion ports if thawed in a water bath. 7. Gently mix the contents of the bag to disperse clumps of cellular material. If visible cell clumps remain, continue to gently mix the contents of the bag. Most small clumps of cellular material should disperse with gentle manual mixing. • Do not shake the bag. • Do not filter, wash, spin down and/or resuspend KRESLADI in new media prior to infusion. • Do not sample, alter, irradiate, or refreeze KRESLADI. 2.3 Administration Complete KRESLADI infusion within 30 minutes of the start of thaw. Do not use an in-line blood filter or infusion pump. Use central venous access for the infusion of KRESLADI. Before infusion, confirm the patient's identity matches the patient identifiers on the KRESLADI infusion bag(s). Do not use KRESLADI if the information on the patient-specific label does not match the intended patient. Use the Lot Information Sheet to confirm the total number of infusion bags to be administered. Prime the tubing of the infusion set with normal saline prior to infusion. Expose the sterile port on the infusion bag by tearing off the protective wrap covering the port. Connect the port to the primed infusion tubing and then connect the tubing to the patient's central venous access aseptically per institutional standard operating procedures. Administer the entire contents of the KRESLADI bag by intravenous infusion. The time for infusion will vary but will usually be less than 10 minutes. At the end of the infusion, flush the infusion bag and tubing with normal saline solution to ensure as many cells as possible are delivered to the patient. Consider the infusion volume in relation to the age and weight of the patient and the priming volume of the infusion tubing set. If two infusion bags are provided, administer the contents of the first infusion bag completely before proceeding to thaw (following Section 2.2 steps 4 - 7) and infuse (following Section 2.3 steps 1 - 6) 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. KRESLADI contains human blood cells that are genetically modified with replication-incompetent, self-inactivating lentiviral vector (LVV). Follow universal precautions and local institutional biosafety guidelines for handling and disposal of KRESLADI to avoid potential transmission of infectious diseases. After KRESLADI Administration Follow standard procedures for patient monitoring and management after HSC transplantation after KRESLADI infusion. Irradiate any blood products required within the first 3 months after KRESLADI infusion. Patients treated with KRESLADI should not donate blood, organs, tissues, or cells at any time in the future.

4 CONTRAINDICATIONS None. None. ( 4 )

6 ADVERSE REACTIONS The most common non-laboratory adverse reactions (≥ 30%): mucositis, upper respiratory tract infection, viral infection, febrile neutropenia, skin lesion, nausea/vomiting, rash/dermatitis, pyrexia, device related infection, and skin infection. ( 6.1 ) The most common laboratory adverse reactions (≥ 30%): hemoglobin decreased, platelet count decreased, neutrophil count decreased, leukocyte count decreased, aspartate aminotransferase increased, and alanine aminotransferase increased. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Rocket Pharmaceuticals at 1-800-982-2410 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience As clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety data described in this section reflect exposure to KRESLADI in one clinical study (Study RP-L201-0318). A total of 9 pediatric patients with severe LAD-I received a single dose of intravenous KRESLADI with a median dose of 4.3 × 10 6 CD34+ cells/kg (range: 2.8 to 10 CD34+ cells/kg) [see Clinical Studies (14) ]. The median duration of follow up after KRESLADI administration was 4.2 years (range: 3.6 to 5.7 years). Serious adverse reactions were reported in 4 patients (44%) including serious infections (n=4), pulmonary arterial hypertension (n=1), sensorineural deafness (n=1), and veno-occlusive disease (n=1). Table 1 presents the most common adverse reactions reported in Study RP-L201-0318. Table 1: Non-Laboratory Adverse Reactions Reported in ≥ 20% of Patients in Study RP-L201-0318 (N=9) Adverse Reaction All Grades (%) Grade ≥3 (%) Gastrointestinal disorders Note: Adverse reactions are defined as adverse events that occurred from myeloablative conditioning administration through year 2 following KRESLADI administration. Nausea/Vomiting Includes multiple related terms 4 (44%) 0 Constipation 2 (22%) 0 General disorders and administration site conditions Mucositis 8 (89%) 5 (56%) Febrile neutropenia 6 (67%) 6 (67%) Pyrexia 3 (33%) 0 Infections and infestations Upper respiratory tract infection 8 (89%) 5 (56%) Viral infection 7 (78%) 1 (11%) Skin infection 3 (33%) 0 Device-related infection Device-related infection includes vascular device infection, device related bacteremia, and bacteremia that occurred with a central line in place 3 (33%) 2 (22%) Lower respiratory tract infection 2 (22%) 1 (11%) Gastroenteritis 2 (22%) 1 (11%) Skin candidiasis 2 (22%) 0 Urinary tract infection 2 (22%) 0 Skin and subcutaneous tissue disorders Skin lesion Skin lesion includes pyoderma gangrenosum, skin lesion, aseptic pustule, lip erythema, hand erythema, skin erythema at port site, and skin hyperpigmentation 6 (67%) 1 (11%) Rash Rash includes rash, eczema, atopic dermatitis and diaper dermatitis 4 (44%) 0 Alopecia 2 (22%) 0 Table 2 presents laboratory abnormalities that worsened from baseline in ≥20% of patients in Study RP-L201-0318. Table 2: Laboratory Abnormalities that Worsened from Baseline Reported in ≥ 20% of Patients in Study RP-L201-0318 (N=9) Baseline laboratory values were assessed prior to myeloablative conditioning Laboratory Abnormality All events occurred within 30 days post-infusion except for liver enzymes increased, which occurred in 3 patients within 30 days and in one patient after 90 days post-infusion All Grades (%) Grade ≥ 3 (%) Hemoglobin decreased 9 (100%) 9 (100%) Platelet count decreased 9 (100%) 9 (100%) Neutrophil count decreased 9 (100%) 9 (100%) Leukocyte count decreased 5 (56%) 5 (56%) Aspartate aminotransferase increased 4 (44%) 0 Alanine aminotransferase increased 3 (33%) 0

What is KRESLADI used for?
1 INDICATIONS AND USAGE KRESLADI is indicated for the treatment of 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. This indication is approved under accelerated approval based on increase in neutrophil CD18 and CD11a …

Who makes KRESLADI?
Rocket Pharmaceuticals, Inc. is the labeler of record for KRESLADI.

What form does KRESLADI come in?
administered by intravenous. Strengths and pack sizes vary by label, so compare the NDC on your pack with the identifier listed on this page.

Is KRESLADI prescription or over-the-counter?
The FDA label for this product is recorded as cellular therapy. Marketing status can differ between strengths and countries, so check the dispensing rules where you live.

Has KRESLADI been recalled?
No FDA recall record in our database matches this product name or manufacturer. Recall data is updated periodically, so a very recent notice may not appear here yet.

Where does this information come from?
All content is reproduced from FDA Structured Product Labelling data via openFDA. It is provided for identification and reference only and is not medical advice.