Autologous CD34+ enriched cell fraction that contains CD34+ cells transduced with retroviral vector that encodes for the human ADA cDNA sequence, sold under the brand name Strimvelis, is a

medication A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy ( pharmacotherapy) is an important part of the medical field an ...

used to treat severe

combined immunodeficiency Combined immunodeficiencies (or combined immunity deficiency) are immunodeficiency disorders that involve multiple components of the immune system, including both humoral immunity and cell-mediated immunity. This category includes conditions su ...

due to

adenosine deaminase deficiency Adenosine deaminase deficiency (ADA deficiency) is a metabolic disorder that causes immunodeficiency. It is caused by mutations in the ADA gene. It accounts for about 10–15% of all cases of autosomal recessive forms of severe combined immuno ...

(ADA-SCID). The most common side effect is pyrexia (fever). Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged. ADA-SCID is a rare inherited condition in which there is a change (mutation) in the gene needed to make an enzyme called adenosine deaminase (ADA). As a result, people lack the ADA enzyme. Because ADA is essential for maintaining healthy lymphocytes (white blood cells that fight off infections), the immune system of people with ADA-SCID does not work properly and without effective treatment they rarely survive more than two years. Strimvelis is the first ''ex vivo'' autologous gene therapy approved by the European Medicines Agency (EMA).

Medical uses

Strimvelis is indicated for the treatment of people with severe combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID), for whom no suitable human leukocyte antigen (HLA)-matched related stem cell donor is available.

Treatment

The treatment is personalized for each person;

hematopoietic stem cell Hematopoietic stem cells (HSCs) are the stem cells that give rise to other blood cells. This process is called haematopoiesis. In vertebrates, the very first definitive HSCs arise from the ventral endothelial wall of the embryonic aorta withi ...

(HSCs) are extracted from the person and purified so that only

CD34 CD34 is a transmembrane phosphoglycoprotein protein encoded by the CD34 gene in humans, mice, rats and other species. CD34 derives its name from the cluster of differentiation protocol that identifies cell surface antigens. CD34 was first descri ...

-expressing cells remain. Those cells are cultured with cytokines and

growth factors A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. Usually it is a secreted protein or a steroid hormone. Growth factors are important for re ...

and then transduced with a

gammaretrovirus Gammaretrovirus is a genus in the ''Retroviridae'' family. Example species are the murine leukemia virus and the feline leukemia virus. They cause various sarcomas, leukemias and immune deficiencies in mammals, reptiles and birds. Introduction ...

containing the human

adenosine deaminase Adenosine deaminase (also known as adenosine aminohydrolase, or ADA) is an enzyme () involved in purine metabolism. It is needed for the breakdown of adenosine from food and for the turnover of nucleic acids in tissues. Its primary function i ...

gene and then reinfused into the person. These cells take root in the person's

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 hematopoieti ...

, replicating and creating cells that mature and create normally functioning adenosine deaminase protein, resolving the problem. As of April 2016, the transduced cells had a shelf life of about six hours. Prior to extraction, the person is treated with

granulocyte colony-stimulating factor Granulocyte colony-stimulating factor (G-CSF or GCSF), also known as colony-stimulating factor 3 (CSF 3), is a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream. Functiona ...

in order to increase the number of stem cells and improve the harvest; after that but prior to reinfusion, the person is treated with

busulfan Busulfan (Myleran, GlaxoSmithKline, Busulfex IV, Otsuka America Pharmaceutical, Inc.) is a chemotherapy drug in use since 1959. It is a cell cycle non-specific alkylating antineoplastic agent, in the class of alkyl sulfonates. Its chemical de ...

melphalan Melphalan, sold under the brand name Alkeran among others, is a chemotherapy medication used to treat multiple myeloma, ovarian cancer, melanoma, and AL amyloidosis. It is taken by mouth or by injection into a vein. Common side effects inclu ...

to kill as many of the person's existing HSCs to increase the chances of the new cells' survival.

Side effects

The most common side effect is pyrexia (fever). Serious side effects may include effects linked to autoimmunity (when the immune system attacks the body's own cells) such as

hemolytic anemia Hemolytic anemia or haemolytic anaemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells (RBCs), either in the blood vessels (intravascular hemolysis) or elsewhere in the human body (extravascular). This most commonly ...

(low red blood cell counts due to their too rapid breakdown),

aplastic anemia Aplastic anemia is a cancer in which the body fails to make blood cells in sufficient numbers. Blood cells are produced in the bone marrow by stem cells that reside there. Aplastic anemia causes a deficiency of all blood cell types: red blood ...

(low blood cell counts due to damaged bone marrow),

hepatitis Hepatitis is inflammation of the liver parenchyma, liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), Anorexia (symptom), poor appetite ...

(liver inflammation),

thrombocytopenia Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care patients and is seen in a fifth of medical patients a ...

(low blood platelet count) and Guillain-Barré syndrome (damage to nerves that can result in pain, numbness, muscle weakness and difficulty walking). Leukemia is a risk of treatment with Strimvelis.

History

The treatment was developed at San Raffaele Telethon Institute for Gene Therapy and developed by

GlaxoSmithKline GSK plc, formerly GlaxoSmithKline plc, is a British Multinational corporation, multinational pharmaceutical and biotechnology company with global headquarters in London, England. Established in 2000 by a Mergers and acquisitions, merger of Gl ...

(GSK) through a 2010 collaboration with Fondazione Telethon and Ospedale San Raffaele. GSK, working with the biotechnology company

MolMed MOLMED is a biotechnology company founded in 1996 in Milan. It originally operated as contract manufacturing organization and other services for companies developing gene therapy and cell therapy products. In 2000, the company changed its busines ...

S.p.A., developed a manufacturing process that was previously only suitable for

clinical trials Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...

into one demonstrated to be robust and suitable for commercial supply. In April 2016, a committee at the European Medicines Agency (EMA) recommended marketing approval for its use in children with

, for whom no matched HSC donor is available, on the basis of a clinical trial that produced a 100% survival rate; the median follow-up time was 7 years after the treatment was administered. 75% of people who received the treatment needed no further

enzyme replacement therapy Enzyme replacement therapy (ERT) is a medical treatment which replaces an enzyme that is deficient or absent in the body. Usually, this is done by giving the patient an intravenous (IV) infusion of a solution containing the enzyme. ERT is availa ...

. Efforts had begun 14 years before. The total number of children treated was reported as 22 and 18. Around 80% of patients have no matched donor. Strimvelis was approved by the

European Commission The European Commission (EC) is the executive of the European Union (EU). It operates as a cabinet government, with 27 members of the Commission (informally known as "Commissioners") headed by a President. It includes an administrative body ...

on 27 May 2016. As of 2016, the only site approved to manufacture the treatment was MolMed.Ben Adams for FierceBiotech Apr 4, 201
Strimvelis to be the start of a whole new gene therapy platform for GSK and partners
/ref> In 2017, GSK announced it was looking to sell off Strimvelis, and in March 2018, GSK sold Strimvelis to Orchard Therapeutics Ltd.; as of that time there had been only five sales of the product.

Society and culture

The condition affects about 14 people per year in Europe and 12 in the U.S.

Economics

The price for the treatment was set at , twice the annual cost of

injections.

Enzyme replacement therapy Enzyme replacement therapy (ERT) is a medical treatment which replaces an enzyme that is deficient or absent in the body. Usually, this is done by giving the patient an intravenous (IV) infusion of a solution containing the enzyme. ERT is availa ...

for ADA requires weekly injections and costs about for one patient over ten years.

Names

''Strimvelis'' is the brand name. The common name is ''autologous CD34+ enriched cell fraction that contains CD34+ cells transduced with retroviral vector that encodes for the human ADA cDNA sequence''.