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. It is currently undergoing Phase I/II of clinical trials that are expected to conclude in October 2025.
Development history
OTL-103 is based on the lentiviral vector technology licensed from GlaxoSmithKline by Orchard Therapeutics in 2020. In 2019, the Food and Drug Administration granted OTL-103 Regenerative Medicine Advanced Therapy status. 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. Orchard Therapeutics expected to file a Biologics License Application with the Food and Drug Administration in 2021, however, due to the COVID-19 pandemic's impact on drug development, this was postponed to 2022.
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. 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.
References
- ^ 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.
- ^ 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.
- 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 (Press release). Retrieved 2021-06-28.
- Pol, Jennifer (2019-07-31). "Orchard Therapeutics gets FDA RMAT designation for Wiskott-Aldrich Syndrome drug". BioTuesdays. Retrieved 2021-06-28.
- "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.
- "Orchard Therapeutics' OTL-103 US application for immunodeficiency disorder, pushed to 2022 (NASDAQ:ORTX) | Seeking Alpha". seekingalpha.com. 12 January 2021. Retrieved 2021-06-28.
- "OTL-103 for Wiskott-Aldrich syndrome | Innovation Observatory". www.io.nihr.ac.uk. Retrieved 2021-06-28.
 | This medical treatment–related article is a stub. You can help Misplaced Pages by expanding it. |