Gene therapy is the latest breakthrough in human health

This European website, initiated and developed by CSL Behring, has two separate sections with the aim to provide information on haemophilia for an international audience, either to European healthcare professionals or to the general public.*

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In the last decade, gene therapy has become a treatment reality for genetic diseases and chronic conditions.^1-6

Person with white rubber gloves working in a lab

ABOUT GENE THERAPY

The overall goal of gene therapy is to use therapeutic genes so that symptoms of a disease are improved, prevented or even cured, all while minimizing adverse effects.^7,8

Scientific research into gene therapy began over 50 years ago⁹ and was first successfully administered in 1990.¹⁰ Since that time, more than 2500 clinical studies have been initiated¹ and several products have gained approval by both the European Medicines Agency (EMA) and the United States (US) Food and Drug Administration (FDA).^1-6 In fact, based on the current success rate of trials, the FDA predicts it will be approving 10 to 20 gene therapies every year by 2025.¹¹

Research Progress

50+

Years of ongoing research into gene therapy⁹

2,5k+

Active clinical trials in genetic therapy research^1,12

24%

of active clinical trials are of AAV vector-based technologies¹³

5+

AAV vector-based gene therapies approved by the EMA or the FDA^2-6

Do you know how long scientists have been exploring gene therapy?

How many clinical trials into genetic therapy are currently ongoing?

How often is gene therapy administered and how long does it last?

How many gene therapy products have been approved?

20+

As of 2023, there are over twenty approved gene therapies worldwide, more than ten of which are approved for use in Europe. These gene therapies have been approved for genetic diseases such as adenosine deaminase deficiency, Leber’s congenital amaurosis and spinal muscular atrophy and conditions such as acute lymphocytic leukaemia and diffuse large B-cell lymphoma. The years 2022 and 2023 saw the approval of the first gene therapy treatments for haemophilia. ^2-6,15-24

How Gene Therapies Work

GENE THERAPY IN HAEMOPHILIA

Each gene therapy is specific for the condition it was designed for. Because of this, there is no “one size fits all” gene therapy. Instead, scientists use a strategy which is most likely to succeed based on which gene(s) are causing a disease and which cells in the body are affected.¹

GENE THERAPY IN HAEMOPHILIA

There are different methods of gene therapy application, such as in vivo gene therapy, ex vivo gene therapy and gene editing.¹

in vivo Gene Therapy

An in vivo—or in a living organism—approach is used to deliver a transgene – a therapeutic gene – to certain cells inside the body. The transgene is a blueprint for how that cell can produce proteins like someone without the disease. This blueprint is packaged in a delivery vehicle, most often a viral vector (learn more below). Once delivered, the cell processes that blueprint and starts making proteins as instructed by the transgene. This means the cell will now act as if it did not have the genetic disease.^1,25

By 2023, the first gene therapies were approved for the treatment of haemophilia A and B in Europe and in the USA. The therapeutic genes are delivered using adeno-associated virus vectors.^4-6,26

Hand in rubber glow picking up a samples in a lab

ex vivo Gene Therapy

An ex vivo—or outside a living organism—approach is used to replace a defective gene or insert a transgene outside the body. Scientists do this by removing cells, like stem cells, from an individual with disease and changing the DNA using a vector (delivery vehicle) in the laboratory. These cells, now containing the transgene, are delivered back to that individual, essentially erasing evidence of the genetic disease.^1,7 This type of therapy was first approved for use in 2016 by the EMA⁷ and is the strategy for 75% of approved therapies,¹⁵ such as melanoma, acute lymphoblastic leukaemia, and β-thalassemia.^1,7

Scientist working with green gloves in a lab

Gene editing

The goal of gene editing is to make changes to the genetic code, by replacing, inserting or removing the regions associated with disease.¹ Unlike in vivo and ex vivo methods which use vectors (delivery vehicles), gene editing methods often use machinery from bacteria, like something called CRISPR. CRISPR is a flexible tool some bacteria use to repair its own damaged DNA by recognising flaws and repairing the problem areas.²⁷ In 2020, the Nobel Prize in Chemistry was awarded to Drs. Emmanuelle Charpentier and Jennifer Doudna for their work on CRISPR-Cas9.²⁸

Although no products have been commercially approved for therapeutic use, there have been clinical trials using gene editing for the treatment of diseases such as Leber congenital amaurosis, a genetic vision disease.²⁷

Vectors in Gene Therapy

More About AAV-Based Gene Therapy

To deliver a transgene – therapeutic gene – to cells in your body, the genetic blueprint must be packaged so that it is not destroyed by your immune system. Viruses have evolved the ability to hide from your immune system so that they can infect your cells and produce more virus. Scientists have learned how to use this ability without actually infecting you with the virus.⁸

Gene therapy uses a delivery vehicle, called a vector, that can enter certain cells. This vector can be produced from a modified, non-infectious viral shell.⁸ Infused into a person with the same kind of needle used to administer factor replacement products, vectors act as delivery trucks, carrying a package of genetic blueprints to specific cells.²⁵ Once delivered, the package acts like a generator that plugs into the cellular machinery, allowing a person to continually generate their own stable proteins like someone who does not have the genetic disease.^8,25

More About AAV-Based Gene Therapy

Gene technologies use multiple types of vectors,¹² the most common include:

Scientists have been exploring gene therapy as a potential treatment approach for well over 50 years.⁹ In the past decade several AAV vector products have been approved by the EMA or by the FDA.^2-6 Gene therapies are currently being researched in many clinical trials for a variety of indications,^1,12 such as haemophilia A³⁰ and B.¹⁴

1986

Successful Delivery of a Gene Therapy to Mammalian Cells

Mouse cells which had a defective gene were corrected after injection with a transgene, proving that gene therapy is possible in the laboratory.^27,31

1990

First Gene Therapy Trial for People

A 4-year-old girl with adenosine deaminase (ADA)-deficient severe combined immunodeficiency disease (SCID) was successfully treated with a retroviral-based gene therapy.¹⁰ Today she is in her 30s and is an active member of the rare disease community.³²

2005

First AAV Vector Gene Therapy Trial for Haemophilia B

In a proof-of-concept study, scientists showed that an intramuscular in vivo delivery of an AAV vector successfully treated haemophilia B in a canine model.³³

2017

FDA Approves its First Gene Therapy

The FDA approved a gene therapy for children and young adults with acute lymphoblastic leukaemia.³⁴

2018

First AAV Vector Gene Therapy is Approved by the EMA

The EMA approved an AAV-based gene therapy for inherited retinal dystrophy.²

2020

The EMA Approves a Second AAV Vector Gene Therapy

The EMA approved a second AAV-based gene therapy for spinal muscular atrophy.³

2022-2023

First Gene Therapies for Haemophilia Approved in Europe and in the USA

In 2022 and 2023, the first adeno-associated virus vector-based gene therapies for the treatment of adults with haemophilia A and B were approved in Europe and in the USA.^4-6,26

Today

Genetic Therapy Research is Ongoing

There are currently thousands of ongoing clinical trials with AAV vector gene therapies for the treatment of many genetic diseases and chronic conditions.^1,12

Available Treatments for Haemophilia

How have treatment options for patients with haemophilia advanced over the years and what options are currently available?

Gene Therapy for Haemophilia

Learn about what makes haemophilia the optimal candidate for a gene therapy.

References

Anguela XM, High KA. Entering the modern era of gene therapy. Annu Rev Med. 2019;70:273-288.
European Medicines Agency. Luxturna. https://www.ema.europa.eu/en/medicines/human/EPAR/luxturna. Accessed November 5, 2021.
European Medicines Agency. Zolgensma. https://www.ema.europa.eu/en/medicines/human/EPAR/zolgensma. Accessed November 5, 2021.
Food and Drug Administration. Approved Cellular and Gene Therapy Products. https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/approved-cellular-and-gene-therapy-products. Accessed September 5, 2023.
European Medicines Agency (EMA). Roctavian. https://www.ema.europa.eu/en/medicines/human/EPAR/roctavian-0. Accessed January 28, 2023.
European Medicines Agency (EMA). Hemgenix. https://www.ema.europa.eu/en/medicines/human/EPAR/hemgenix. Accessed January 28, 2023.
High KA, Roncarolo MG. Gene therapy. N Engl J Med. 2019;381(5):455-464.
McCain J. The future of gene therapy. Biotechnol Healthc. 2005;2(3):52-54,56-60.
Friedmann T, Roblin R. Gene therapy for human genetic disease? Science. 1972;175(4025):949-955.
Muul LM, Tuschong LM, Soenen SL, et al. Persistence and expression of the adenosine deaminase gene for 12 years and immune reaction to gene transfer components: long-term results of the first clinical gene therapy trial. Blood. 2003;101(7):2563-2569.
Statement from FDA Commissioner Scott Gottlieb, M.D. and Peter Marks, M.D., Ph.D., Director of the Center for Biologics Evaluation and Research on new policies to advance development of safe and effective cell and gene therapies. [press release]. Silver Spring, Maryland, USA: US Food and Drug Administration (FDA). https://www.fda.gov/news-events/press-announcements/statement-fda-commissioner-scott-gottlieb-md-and-peter-marks-md-phd-director-center-biologics. Published January 15, 2019. Accessed November 5, 2021.
Ghosh S, Brown AM, Jenkins C, Campbell K. Viral vector systems for gene therapy: a comprehensive literature review of progress and biosafety challenges. Appl Biosaf. 2020;25(1):7-18.
Food and Drug Administration (FDA) Cellular, Tissue, and Gene Therapies Advisory Committee Meeting #70. Toxicity Risks of Adeno-associated Virus (AAV) Vectors for Gene Therapy (GT). Published September 2021.
Nathwani AC. Gene therapy for hemophilia. Hematology Am Soc Hematol Educ Program. 2019;2019(1):1-8.
American Society of Gene and Cell Therapy (ASGCT) and Pharma Intelligence. Q3 2021 Quarterly Data Report on Gene, Cell, & RNA Therapy Landscape. Accessed December 1, 2021.
European Medicines Agency. Imlygic. https://www.ema.europa.eu/en/medicines/human/EPAR/imlygic. Accessed November 5, 2021.
European Medicines Agency. Strimvelis. https://www.ema.europa.eu/en/medicines/human/EPAR/strimvelis. Accessed November 5, 2021.
European Medicines Agency. Kymriah. https://www.ema.europa.eu/en/medicines/human/EPAR/kymriah. Accessed November 5, 2021.
European Medicines Agency. Yescarta. https://www.ema.europa.eu/en/medicines/human/EPAR/yescarta. Accessed November 5, 2021.
European Medicines Agency. Zynteglo. https://www.ema.europa.eu/en/medicines/human/EPAR/zynteglo. Accessed November 5, 2021.
European Medicines Agency. Tecartus. https://www.ema.europa.eu/en/medicines/human/EPAR/tecartus. Accessed November 5, 2021.
European Medicines Agency. Libmeldy. https://www.ema.europa.eu/en/medicines/human/EPAR/libmeldy. Accessed November 5, 2021.
European Medicines Agency. Abecma. https://www.ema.europa.eu/en/medicines/human/EPAR/abecma. Accessed November 5, 2021.
European Medicines Agency. Skysona. https://www.ema.europa.eu/en/medicines/human/EPAR/skysona. Accessed November 5, 2021.
Wang D, Tai PWL, Gao G. Adeno-associated virus vector as a platform for gene therapy delivery. Nat Rev Drug Discov. 2019;18(5):358-378.
FDA Approves First Gene Therapy to Treat Adults with Hemophilia B [press release]. Silver Spring, Maryland, USA: US Food and Drug Administration (FDA). https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-treat-adults-hemophilia-b. November 22, 2022. Accessed January 5, 2023.
Bak RO, Gomez-Ospina N, Porteus MH, Gene Editing on center stage. Trends Genet. 2018;34(8):600-611.
Ledford H, Callaway E. Pioneers of CRISPR gene editing win chemistry Nobel. Nature. 2020;586:346-347.
Bulcha JT, Wang Y, Ma H, et al. Viral vector platforms within the gene therapy landscape. Signal Transduct Target Ther. 2021;6(1):53.
Rangarajan S, Walsh L, Lester W, et al. AAV5-Factor VIII gene transfer in severe hemophilia A. N Engl J Med. 2017;377(26):2519-2530.
Thomas KR, Folger KR, Capecchi MR. High frequency targeting of genes to specific sites in the mammalian genome. Cell. 1986;44:419-428.
Boston Children’s Hospital. After decades of evolution, gene therapy arrives. https://answers.childrenshospital.org/gene-therapy-history/. Published December 22, 2020. Accessed November 17, 2021.
Arruda V, Stedman H, Jian H, et al. Correction of hemophilia B phenotype by novel method of regional intravenous delivery of AAV vector to skeletal muscle of hemophilia B dogs. Mol Ther. 2005;11:S233.
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GENE THERAPY IS THE LATEST BREAKTHROUGH IN HUMAN HEALTH

Understanding What Gene Therapy Is

Current Progress in Genetic Therapy Research

50+

2,5k+

24%

5+

The Numbers Behind Gene Therapy

Gene Therapies Can be Tailored to Treat Multiple Conditions

CURRENT STRATEGIES FOR DELIVERING THERAPEUTIC GENES