OTL-103

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, cancers and

References
  1. Jackson, Christina (2020-07-23). "Orchard Therapeutics Inks Deal for GSK's Stable Cell Line Technology". GEN - Genetic Engineering and Biotechnology News. Retrieved 2021-06-28.
  2. Orchard Therapeutics (2020-12-04). "A Single Arm, Open-label Clinical Trial of Hematopoietic Stem Cell Gene Therapy With Cryopreserved Autologous CD34+ Cells Transduced With Lentiviral Vector Encoding WAS cDNA in Subjects With Wiskott-Aldrich Syndrome (WAS)". Ospedale San Raffaele. {{cite journal}}: Cite journal requires |journal= (help)
  3. Orchard Therapeutics (Europe) Limited (2019-07-29). "Orchard Therapeutics Announces FDA Regenerative Medicine Advanced Therapy (RMAT) Designation Granted for OTL-103 for the Treatment of Wiskott-Aldrich Syndrome". GlobeNewswire News Room. Retrieved 2021-06-28.{{cite web}}: CS1 maint: url-status (link)
  4. Pol, Jennifer (2019-07-31). "Orchard Therapeutics gets FDA RMAT designation for Wiskott-Aldrich Syndrome drug". BioTuesdays. Retrieved 2021-06-28.
  5. "Orchard Therapeutics Announces 2021 Corporate Priorities Supporting the Build-out of its Commercial Business in Hematopoietic Stem Cell (HSC) Gene Therapy and Expansion of its Clinical Applications | Seeking Alpha". seekingalpha.com. Retrieved 2021-06-28.
  6. "Orchard Therapeutics' OTL-103 US application for immunodeficiency disorder, pushed to 2022 (NASDAQ:ORTX) | Seeking Alpha". seekingalpha.com. Retrieved 2021-06-28.
  7. "OTL-103 for Wiskott-Aldrich syndrome | Innovation Observatory". www.io.nihr.ac.uk. Retrieved 2021-06-28.


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