As atidarsagene autotemcel is not intended for use in adults, human data on use during pregnancy and animal reproduction studies are not available.
As atidarsagene autotemcel is not intended for use in adults, human data on use during lactation are not available.
With regard to fertility, consult the SmPC of the myeloablative conditioning medicinal product. It should be noted that the treating physician should inform the patient’s parents/carers about options for cryopreservation of spermatogonial stem cells or ovarian tissue.
Not relevant.
The safety of atidarsagene autotemcel was evaluated in 35 patients with MLD.
The median duration of follow-up in the integrated safety data set, which included 29 patients treated with the fresh (investigational) formulation was 4.51 years (range: 0.64 to 8.85 years). Three patients died and a total of 26 patients remained in the follow-up phase.
The median duration of follow-up in the 6 patients treated with the cryopreserved (commercial) formulation was 0.87 years (range: 0.0 to 1.47 years). All of them remained in the follow-up phase.
Given the small patient population, adverse reactions in the table below do not provide a complete perspective on the nature and frequency of these events.
Treatment with atidarsagene autotemcel is preceded by medical interventions, namely haematopoietic stem cell collection through peripheral blood mobilisation with G-CSF with or without plerixafor followed by apheresis, and myeloablative conditioning (preferably using busulfan), which carry their own risks. When assessing the safety of a treatment with atidarsagene autotemcel, the safety profile and product information of the medicinal products used for peripheral blood mobilisation and myeloablative conditioning should be considered, in addition to the risks linked to the gene therapy.
Adverse reactions are listed by MedDRA body system organ class and by frequency. Frequencies are defined as: very common (≥1/10), and common (≥1/100 and <1/10).
Table 1. Adverse reactions attributed to atidarsagene autotemcel:
| System Organ Class | Very Common | Common |
|---|---|---|
| Immune system disorders | Antibody Test Positive (Anti ARSA Antibody) |
Table 2. Adverse reactions potentially attributed to myeloablative conditioning*:
| System Organ Class | Very Common | Common |
|---|---|---|
| Infections and infestations | Cytomegalovirus viraemia, Pneumonia, Staphylococcal infection, Urinary tract infection, Viral infection | |
| Blood and lymphatic system disorders | Febrile neutropenia, Neutropenia | Anaemia, Thrombocytopenia |
| Metabolism and nutrition disorders | Metabolic acidosis | Fluid overload |
| Psychiatric disorders | Insomnia | |
| Nervous system disorders | Headache | |
| Respiratory, thoracic and mediastinal disorders | Epistaxis, Oropharyngeal pain | |
| Gastrointestinal disorders | Stomatitis, Vomiting | Ascites, Diarrhoea, Gastrointestinal haemorrhage, Nausea |
| Hepatobiliary disorders | Hepatomegaly, Veno-occlusive liver disease | Hypertransaminasaemia |
| Skin and subcutaneous tissue disorders | Skin exfoliation | |
| Musculoskeletal and connective tissue disorders | Back pain, Bone pain | |
| Renal and urinary disorders | Oliguria | |
| Reproductive system and breast disorders | Ovarian failure | |
| General disorders and administration site conditions | Pyrexia | |
| Investigations | Alanine aminotransferase increased, Aspartate aminotransferase increased, Aspergillus test positive |
* Based on 29 patients who have undergone myeloablative conditioning by busulfan in the integrated data set.
Five out of 35 patients tested positive for anti-ARSA antibodies (AAA) at various post-treatment time points and had the event “Antibody test positive / Presence of antibodies against arylsulfatase A” reported by the Investigator. Antibody titres were generally low and resolved either spontaneously or after a short course of rituximab.
In all patients with positive AAA test results, no negative effects were observed in the post-treatment ARSA activity of peripheral blood or bone marrow cellular subpopulations nor in the ARSA activity within the cerebrospinal fluid.
Patients treated with atidarsagene autotemcel should be regularly monitored for AAA.
During the clinical studies, haematopoietic stem cell collection was performed either through bone marrow (BM) harvest or peripheral blood mobilisation. The safety profile of BM harvest and mobilisation/apheresis were consistent with the known safety and tolerability of both procedures and the SmPC of mobilisation agents (G-CSF and plerixafor).
No serious adverse events were reported as potentially attributable to BM harvest within the range of BM volumes harvested (median volume was 35.5 mL/kg; range: 15.1-56.4 mL/kg). In the Integrated Safety Set (n=29), one patient experienced bone pain, which was qualified as a grade 2 adverse event and deemed related to the BM harvest procedure, but unrelated to the volume harvested.
No serious adverse events were reported as potentially attributable to mobilisation and apheresis and none of the patients who underwent mobilisation experienced any adverse events in the pre-treatment phase which could have been attributed to the mobilising agents.
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