Long‑Term Monitoring of Insertional Oncogenesis–Related Malignancy Risk in Early‑Onset Metachromatic Leukodystrophy Patients Treated with Atidarsagene Autotemcel (OTL‑200)

The primary objective is to assess the long‑term safety of atidarsagene autotemcel (Libmeldy) by monitoring the incidence of malignancy associated with insertional oncogenesis in patients with metachromatic leukodystrophy who receive the investigational therapy. This evaluation addresses a critical safety concern for gene‑transfer products, providing data on potential oncogenic risk that may influence risk‑benefit assessments and regulatory decisions.

Six participants were enrolled, comprising both female and male children with early‑onset Metachromatic leukodystrophy. The age range of the cohort spanned approximately 2 to 3 years, reflecting the pediatric and vulnerable nature of the population. All subjects were selected as patients who qualified for Group 1 of the LongTERM‑MLD OTL‑200‑10 Study, receiving OTL‑200 as part of a CDP regimen, and for whom written informed consent was obtained from the patient or a parent/legal guardian. General health status was limited to the underlying leukodystrophy without additional specified comorbidities, and no specific dietary, physical activity, or habit requirements were stipulated. Key inclusion criteria required early‑onset disease and the ability to provide consent; no further exclusion criteria were detailed.

The study, designated as OTL‑200 Long Term Insertional Oncogenesis Study, is a low‑intervention Phase IV trial monitoring the long‑term risk of malignancy due to insertional oncogenesis in patients with early‑onset Metachromatic leukodystrophy who have received a single intravenous infusion of atidarsagene autotemcel (Libmeldy) at a dose of 30 × 10⁶ cells/kg. Enrollment began on 2 June 2026 and is planned to continue until 31 July 2035. After written informed consent, participants complete a screening visit to confirm eligibility and documentation of prior treatment in the LongTERM‑MLD OTL‑200‑10 Study (Group 1). Follow‑up visits are scheduled at regular intervals throughout the observation period to collect samples for evaluation of the primary endpoint, incidence of malignancies attributable to insertional oncogenesis, and the secondary endpoint, incidence of clonal abundance ≥ 30 %. The end‑of‑study visit concludes the monitoring phase. Participant involvement therefore spans the entire observation period, up to the planned study end date.

The investigational product is Libmeldy 2‑10 × 10⁶ cells/mL dispersion for infusion, containing the gene‑modified autologous hematopoietic stem cell product atidarsagene autotemcel. The preparation is supplied as a sterile dispersion for intravenous infusion. Each participant receives a single dose of 30 000 000 cells per kilogram of body weight, administered intravenously over a controlled infusion period.

No additional experimental or comparator agents are administered in this study; participants receive no concomitant investigational therapy. Standard supportive care consistent with local practice may be provided, but no placebo or active control is incorporated.

Infusion is performed in a clinical setting by qualified personnel. The dosing schedule consists of one infusion on Day 1, followed by routine monitoring visits for safety assessments. Compliance with the infusion protocol is documented through infusion logs, vital sign recordings, and laboratory evaluations performed at predefined intervals.