OTL-103 (GSK-2696275) is a gene therapy for

Wiskott–Aldrich syndrome Wiskott–Aldrich syndrome (WAS) is a rare X-linked recessive disease characterized by eczema, thrombocytopenia (low platelet count), immune deficiency, and bloody diarrhea (secondary to the thrombocytopenia). It is also sometimes called the eczem ...

, a rare

primary immunodeficiency Primary immunodeficiencies are disorders in which part of the body's immune system is missing or does not function normally. To be considered a ''primary'' immunodeficiency (PID), the cause of the immune deficiency must not be secondary in nature ( ...

caused by mutations in the gene that codes for Wiskott–Aldrich syndrome protein (WASp). It was developed by

Orchard Therapeutics An orchard is an intentional plantation of trees or shrubs that is maintained for food production. Orchards comprise fruit- or nut-producing trees which are generally grown for commercial production. Orchards are also sometimes a feature of larg ...

in conjunction with

GlaxoSmithKline GSK plc, formerly GlaxoSmithKline plc, is a British multinational pharmaceutical and biotechnology company with global headquarters in London, England. Established in 2000 by a merger of Glaxo Wellcome and SmithKline Beecham. GSK is the ten ...

. 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

in 2020. In 2019, the

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

granted OTL-103

Regenerative Medicine Advanced Therapy Regenerative Medicine Advanced Therapy (RMAT) is a designation given by the Food and Drug Administration to drug candidates intended to treat serious or life-threatening conditions under the 21st Century Cures Act. A RMAT designation allows for acc ...

status. In the same year, the first clinical trial using OTL-103 for severe cases of

began at the

San Raffaele Hospital The San Raffaele Hospital (also ''Istituto scientifico universitario San Raffaele'' or ''ospedale San Raffaele'', ''HSR'' or ''OSR'') is a university hospital situated in Segrate, the Province of Milan, Italy. It was founded in 1969 by don Luigi ...

Milan, Italy Milan ( , , Lombard language, Lombard: ; it, Milano ) is a city in northern Italy, capital of Lombardy, and the List of cities in Italy, second-most populous city proper in Italy after Rome. The city proper has a population of about 1.4 ...

expected to file a

Biologics License Application A biologics license application (BLA) is defined by the U.S. Food and Drug Administration (FDA) as follows: The biologics license application is a request for permission to introduce, or deliver for introduction, a biologic product into inters ...

with the

in 2021, however, due to the

COVID-19 pandemic The COVID-19 pandemic, also known as the coronavirus pandemic, is an ongoing global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The novel virus was first identif ...

'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 Bone marrow is a semi-solid tissue found within the spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It is composed of hematopoietic ce ...

peripheral blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the c ...

. These are then

transfected Transfection is the process of deliberately introducing naked or purified nucleic acids into eukaryotic cells. It may also refer to other methods and cell types, although other terms are often preferred: " transformation" is typically used to desc ...

with a

lentiviral vector Viral vectors are tools commonly used by molecular biologists to deliver genetic material into cell (biology), cells. This process can be performed inside a living organism (''in vivo'') or in cell culture (''in vitro''). Viruses have evolved spec ...

that encodes for a functional

Wiskott–Aldrich syndrome protein The Wiskott–Aldrich Syndrome protein (WASp) is a 502-amino acid protein expressed in cells of the hematopoietic system that in humans is encoded by the ''WAS'' gene. In the inactive state, WASp exists in an autoinhibited conformation with seq ...

. The transfected cells are then reinfused to the patient. The cells migrate to the bone marrow, where they produce functional copies of

. This would mitigate the symptoms of Wiskott-Aldrich syndrome, such as frequent infections, cancers and

References

Gene therapy Experimental drugs Immune system disorders Orphan drugs {{treatment-stub