OTL-103 (GSK-2696275) is a gene therapy for Wiskott–Aldrich syndrome, a rare primary immunodeficiency caused by mutations in the gene that codes for Wiskott–Aldrich syndrome protein (WASp). It was developed by Orchard Therapeutics in conjunction with GlaxoSmithKline.^[1] It is currently undergoing Phase I/II of clinical trials that are expected to conclude in October 2025.^[2]

Development history

OTL-103 is based on the lentiviral vector technology licensed from GlaxoSmithKline by Orchard Therapeutics in 2020.^[1] In 2019, the Food and Drug Administration granted OTL-103 Regenerative Medicine Advanced Therapy status.^[3][4] In the same year, the first clinical trial using OTL-103 for severe cases of Wiskott–Aldrich syndrome began at the San Raffaele Hospital in Milan, Italy.^[2] Orchard Therapeutics expected to file a Biologics License Application with the Food and Drug Administration in 2021,^[5] however, due to the COVID-19 pandemic's impact on drug development, this was postponed to 2022.^[6]

Mechanism of action

OTL-103 is an autologous cell therapy that uses the patient's own CD34+ cells collected from bone marrow or peripheral blood. These are then transfected with a lentiviral vector that encodes for a functional Wiskott–Aldrich syndrome protein. The transfected cells are then reinfused to the patient.^[7] The cells migrate to the bone marrow, where they produce functional copies of Wiskott–Aldrich syndrome protein. This would mitigate the symptoms of Wiskott-Aldrich syndrome, such as frequent infections, autoimmune disorders and cancers.

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