Marnetegragene autotemcel

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. 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.

KRESLADI adds functional copies of the ITGB2 gene into patients' hematopoietic stem cells (HSCs) through transduction of autologous CD34+ cells with LV-RP-201. After KRESLADI infusion, transduced CD34+ HSCs engraft in the bone marrow and differentiate into various cell types, including leukocytes capable of expressing functional CD18 protein. Functional CD18 protein enables formation of the CD18/CD11a heterodimer (Leukocyte Function-Associated Antigen-1, LFA-1) which facilitates leukocyte adhesion to endothelial surfaces and extravasation to infectious and inflammatory sites.

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. Dosing of KRESLADI is based on the number of CD34+ cells in the infusion bag(s) per kg of body weight. The minimum recommended dose is 2.8 × 10 6 CD34+ cells/kg. Full myeloablative conditioning must be administered before infusion of KRESLADI. Verify the patient's identity matches the unique patient identification information on the KRESLADI infusion bag(s) prior to infusion. Do not sample, alter, or irradiate KRESLADI. Do not use an in-line blood filter or infusion pump.

None. None.

Serious Infections: Monitor patients for signs and symptoms of infection before and after KRESLADI infusion and treat appropriately. Administer prophylactic antimicrobials according to institutional guidelines. Veno-Occlusive Disease: 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: Monitor absolute neutrophil counts (ANC) after KRESLADI infusion. If neutrophil engraftment does not occur administer rescue cells. Delayed Platelet Engraftment: Monitor patients for thrombocytopenia and bleeding until platelet engraftment and count recovery. LVV-mediated Insertional Oncogenesis: Monitor patients at least annually for hematologic malignancies for at least 15 years after KRESLADI infusion.

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. 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.

No formal drug interaction studies have been performed. KRESLADI is not expected to interact with the hepatic cytochrome P-450 family of enzymes or drug transporters. Anti-retrovirals: Patients should not take anti-retroviral medications for one month prior to mobilization, or for the expected duration required for elimination of the anti-retroviral medications, and until all cycles of apheresis are completed.

Keep the infusion bag(s) in the cassette(s) and store KRESLADI frozen in the vapor phase of liquid nitrogen at less than or equal to -150°C (≤ -238°F) until ready for thaw and administration. Do not re-freeze after thawing.