Biology: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, autoimmune disorders and cancers.
References
- ↑ 1.0 1.1 Jackson, Christina (2020-07-23). "Orchard Therapeutics Inks Deal for GSK's Stable Cell Line Technology" (in en-US). https://www.genengnews.com/topics/bioprocessing/orchard-therapeutics-inks-deal-for-gsks-stable-cell-line-technology/.
- ↑ 2.0 2.1 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. https://clinicaltrials.gov/ct2/show/NCT03837483.
- ↑ 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" (in en). https://www.globenewswire.com/news-release/2019/07/29/1892716/0/en/Orchard-Therapeutics-Announces-FDA-Regenerative-Medicine-Advanced-Therapy-RMAT-Designation-Granted-for-OTL-103-for-the-Treatment-of-Wiskott-Aldrich-Syndrome.html.
- ↑ Pol, Jennifer (2019-07-31). "Orchard Therapeutics gets FDA RMAT designation for Wiskott-Aldrich Syndrome drug" (in en-CA). https://biotuesdays.com/2019/07/31/orchard-therapeutics-gets-fda-rmat-designation-for-wiskott-aldrich-syndrome-drug/.
- ↑ "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" (in en). https://seekingalpha.com/pr/18145507-orchard-therapeutics-announces-2021-corporate-priorities-supporting-build-out-of-commercial.
- ↑ "Orchard Therapeutics' OTL-103 US application for immunodeficiency disorder, pushed to 2022 (NASDAQ:ORTX) | Seeking Alpha" (in en). https://seekingalpha.com/news/3650836-orchard-therapeutics-otlminus-103-us-application-for-immunodeficiency-disorder-pushed-to-2022.
- ↑ "OTL-103 for Wiskott-Aldrich syndrome | Innovation Observatory". http://www.io.nihr.ac.uk/report/otl-103-for-wiskott-aldrich-syndrome/.
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