Gene Therapies in Research: Approved Therapies

A Number of Gene Therapies Are Being Marketed

  • There have been a number of gene therapies approved by regulatory agencies for use in cancer and monogenic diseases1,2,3,4,5,6

Autologous CD34+ Cells Encoding βA-T87Q-globin Gene 1

First gene therapy approved for the treatment of transfusion-dependent β-thalassemia7
US approval:
EU approval: May 29, 20191
Indication: Transfusion-dependent β-thalassaemia who do not have a β00 genotype, for whom hematopoietic stem cell (HSC) transplantation is appropriate but a HLA-matched, related HSC donor is not available8
Delivery: Ex vivo8
Viral vector: Lentiviral vector8
Gene manipulation strategy: Gene replacement8,9

Autologous CD34+ Cells Encoding the Human ADA cDNA Sequence2

First ex vivo gene therapy to be approved that targets stem cells10
US approval:
EU approval: May 26, 20162
Indication: Severe combined immunodeficiency due to ADA deficiency11
Delivery: Ex vivo11
Viral vector: Retroviral vector11
Gene manipulation strategy: Gene replacement11

Axicabtagene Ciloleucel3

First gene therapy approved for certain types of non-Hodgkin lymphoma12
US approval: October 18, 2017*12
EU approval: August 23, 2018†13
Indication: Adults with certain types of large B-cell lymphomas who have not responded to or relapsed after ≥2 other lines of systemic therapy3,13
Delivery: Ex vivo12
Viral vector: Retroviral vector3
Gene manipulation strategy: Genetic modulation of immune cells3

Onasemnogene Abeparvovec-xioi4

First gene therapy approved for the treatment of spinal muscular atrophy4
US approval: May 24, 20194
EU approval:
Indication: Spinal muscular atrophy in children less than 2 years of age4
Delivery: In vivo4
Viral vector: Adeno-associated viral vector serotype 94,14
Gene manipulation strategy: Gene replacement15

Tisagenlecleucel5

First approved chimeric antigen receptor (CAR) T-cell immunotherapy16
US approval: August 30, 2017 (B-cell precursor ALL)16
May 1, 2018 (large B-cell lymphoma)15
EU approval: August 23, 2018 (B-cell precursor ALL and diffuse large B-cell lymphoma)16
Indication: Pediatric and young adults (up to 25 years of age) with relapsed or refractory B-cell precursor ALL, or adult relapsed or refractory large B-cell lymphoma16,17
Delivery: Ex vivo16
Viral vector: Lentiviral vector17
Gene manipulation strategy: Genetic modulation of immune cells17

Voretigene Neparvovec-rzyl6

First directly administered gene therapy that targets a monogenic disease18
US approval: December 19, 201718
EU approval: November 22, 201819
Indication: Bi-allelic RPE65 mutation-associated retinal dystrophy18,19
Delivery: In vivo18
Viral vector: Adeno-associated viral vector serotype 220
Gene manipulation strategy: Genetic replacement20

Summary/Module Recap

  • There is an increasing number of gene therapies in the early stages of clinical development, including rising numbers in Phase 310,17

  • The FDA attributes this surge in gene therapies to the development of safer and effective vectors18

  • Consequently, approvals of gene therapies are expected to increase over the coming years18

  • Cancer and monogenic diseases have been the primary targets of gene therapy, but its use is now being explored in a diverse range of diseases10

  • A number of different agents have been approved by regulatory agencies for indications such as cancer and genetic diseases 1,2,3,4,5,6

  1. European Commission. Zynteglo. Available at: https://ec.europa.eu/health/documents/community-register/html/h1367.htm. Accessed September 17, 2019.
  2. European Commission. Strimvelis. Available at: https://ec.europa.eu/health/documents/community-register/html/h1097.htm. Accessed September 17, 2019.
  3. Yescarta® [package insert]. 2017. Available at: https://www.yescarta.com/files/yescarta-pi.pdf. Accessed September 17, 2019.
  4. U.S. FDA. News release. May 24, 2019. Available at: https://www.fda.gov/news-events/press-announcements/fda-approves-innovative-gene-therapy-treat-pediatric-patients-spinal-muscular-atrophy-rare-disease. Accessed September 17, 2019.
  5. Kymriah® [package insert]. 2018. Available at: https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/kymriah.pdf. Accessed September 17, 2019.
  6. Luxturna™ [package insert]. 2017. Available at: https://sparktx.com/LUXTURNA_US_Prescribing_Information.pdf. Accessed September 17, 2019.
  7. Bluebird Bio. Press release. June 3, 2019. Available at: https://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-announces-eu-conditional-marketing-authorization. Accessed September 17, 2019.
  8. Zynteglo® [summary of product characteristics]. 2019. Available at: https://www.ema.europa.eu/en/documents/product-information/zynteglo-epar-product-information_en.pdf. Accessed September 17, 2019.
  9. Clinical Trials Arena. Zynteglo for the Treatment of Transfusion-Dependent Beta-thalassemia. Available at: https://www.clinicaltrialsarena.com/projects/zynteglo-beta-thalassemia/. Accessed September 25, 2019.
  10. Ginn SL, et al. J Gene Med 2018;20(5):e3015.
  11. Strimvelis® [summary of product characteristics]. 2018. Available at: https://www.ema.europa.eu/en/documents/product-information/strimvelis-epar-product-information_en.pdf. Accessed September 17, 2019.
  12. U.S. FDA. News release. October 18, 2017. Available at: https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm581216.htm. Accessed September 17, 2019.
  13. European Commission. Yescarta. Available at: https://ec.europa.eu/health/documents/community-register/html/h1299.htm. Accessed September 17, 2019.
  14. Mendell JR, et al. N Engl J Med 2017;377(18):1713–1722.
  15. Cure SMA. Zolgensma. Available at: https://www.curesma.org/zolgensma/. Accessed September 25, 2019.
  16. U.S. FDA. August 30, 2017. Available at: https://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm574154.htm. Accessed September 17, 2019.
  17. The Journal of Gene Medicine. Gene Therapy Clinical Trials Worldwide, December 2018. Available at: https://www.abedia.com/wiley/phases.php. Accessed September 17, 2019.
  18. U.S. FDA. Press announcement. January 15, 2019. Available at: https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm629493.htm. Accessed September 17, 2019.
  1. European Commission. Zynteglo. Available at: https://ec.europa.eu/health/documents/community-register/html/h1367.htm. Accessed September 17, 2019.
  2. European Commission. Strimvelis. Available at: https://ec.europa.eu/health/documents/community-register/html/h1097.htm. Accessed September 17, 2019.
  3. Yescarta® [package insert]. 2017. Available at: https://www.yescarta.com/files/yescarta-pi.pdf. Accessed September 17, 2019.
  4. U.S. FDA. News release. May 24, 2019. Available at: https://www.fda.gov/news-events/press-announcements/fda-approves-innovative-gene-therapy-treat-pediatric-patients-spinal-muscular-atrophy-rare-disease. Accessed September 17, 2019.
  5. Kymriah® [package insert]. 2018. Available at: https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/kymriah.pdf. Accessed September 17, 2019.
  6. Luxturna™ [package insert]. 2017. Available at: https://sparktx.com/LUXTURNA_US_Prescribing_Information.pdf. Accessed September 17, 2019.
  7. Bluebird Bio. Press release. June 3, 2019. Available at: https://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-announces-eu-conditional-marketing-authorization. Accessed September 17, 2019.
  8. Zynteglo® [summary of product characteristics]. 2019. Available at: https://www.ema.europa.eu/en/documents/product-information/zynteglo-epar-product-information_en.pdf. Accessed September 17, 2019.
  9. Clinical Trials Arena. Zynteglo for the Treatment of Transfusion-Dependent Beta-thalassemia. Available at: https://www.clinicaltrialsarena.com/projects/zynteglo-beta-thalassemia/. Accessed September 25, 2019.
  10. Ginn SL, et al. J Gene Med 2018;20(5):e3015.
  11. Strimvelis® [summary of product characteristics]. 2018. Available at: https://www.ema.europa.eu/en/documents/product-information/strimvelis-epar-product-information_en.pdf. Accessed September 17, 2019.
  12. U.S. FDA. News release. October 18, 2017. Available at: https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm581216.htm. Accessed September 17, 2019.
  13. European Commission. Yescarta. Available at: https://ec.europa.eu/health/documents/community-register/html/h1299.htm. Accessed September 17, 2019.
  14. Mendell JR, et al. N Engl J Med 2017;377(18):1713–1722.
  15. Cure SMA. Zolgensma. Available at: https://www.curesma.org/zolgensma/. Accessed September 25, 2019.
  16. U.S. FDA. August 30, 2017. Available at: https://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm574154.htm. Accessed September 17, 2019.
  17. The Journal of Gene Medicine. Gene Therapy Clinical Trials Worldwide, December 2018. Available at: https://www.abedia.com/wiley/phases.php. Accessed September 17, 2019.
  18. U.S. FDA. Press announcement. January 15, 2019. Available at: https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm629493.htm. Accessed September 17, 2019.