Elivaldogene autotemcel

SKYSONA is indicated to slow the progression of neurologic dysfunction in boys 4-17 years of age with early, active cerebral adrenoleukodystrophy (CALD) without an available human leukocyte antigen (HLA)-matched donor for allogeneic hematopoietic stem cell transplant. Early, active cerebral adrenoleukodystrophy refers to asymptomatic or mildly symptomatic (neurologic function score, NFS ≤ 1) boys who have gadolinium enhancement on brain magnetic resonance imaging (MRI) and Loes scores of 0.5-9. This indication is approved under accelerated approval based on 24-month Major Functional Disability (MFD)-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

SKYSONA adds functional copies of the ABCD1 cDNA into patients' hematopoietic stem cells (HSCs) through transduction of autologous CD34+ cells with Lenti-D LVV. After SKYSONA infusion, transduced CD34+ HSCs engraft in the bone marrow and differentiate into various cell types, including monocytes (CD14 + ) capable of producing functional ALDP. Functional ALDP can then participate in the local degradation of very long chain fatty acids (VLCFAs), which is believed to slow or possibly prevent further inflammation and demyelination.

For autologous use only. For intravenous use only. Patients must undergo hematopoietic stem cell (HSC) mobilization and apheresis to obtain CD34+ cells for SKYSONA manufacturing. Dosing of SKYSONA is based on the number of CD34+ cells in the infusion bag(s) per kg of body weight. The minimum recommended dose is 5.0 × 10 6 CD34+ cells/kg. Full myeloablative and lymphodepleting conditioning must be administered before infusion of SKYSONA. Verify the patient's identity matches the unique patient identification information on the SKYSONA infusion bag(s) prior to infusion. Do not sample, alter, or irradiate SKYSONA. Do not use an in-line blood filter or an infusion pump.

None. None.

Boxed warning (hematologic malignancy): Hematologic malignancies, including life-threatening cases of myelodysplastic syndrome and acute myeloid leukemia, have occurred in patients treated with SKYSONA. Patients have been diagnosed between 14 months and 10 years after SKYSONA administration, and the cancers appear to be related to treatment with SKYSONA. Serious Infections: Life-threatening bacterial and viral infections may occur. Monitor patients for signs and symptoms of infection. Prolonged Cytopenias: Patients may exhibit cytopenias >1 year after treatment. Monitor patients for bleeding and infection. Delayed Platelet Engraftment: Monitor patients for thrombocytopenia and bleeding until platelet engraftment and count recovery. Risk of Neutrophil Engraftment Failure: Monitor absolute neutrophil counts and if neutrophil engraftment does not occur, give rescue cells.

Most common non-laboratory adverse reactions (≥ 20%): mucositis, nausea, vomiting, febrile neutropenia, alopecia, decreased appetite, abdominal pain, constipation, pyrexia, diarrhea, headache, rash. Most common Grade 3 or 4 laboratory abnormalities (≥ 40%): leukopenia, lymphopenia, thrombocytopenia, neutropenia, anemia, hypokalemia.

Anti-retrovirals: Do not take these medications from at least one month prior to starting mobilization agents until all cycles of apheresis are complete and after the expected duration of elimination.

Store SKYSONA frozen in the vapor phase of liquid nitrogen at less than or equal to -140°C (-220°F) until ready for thaw and administration. Do not re-freeze after thawing.