Gene Therapies in Research: Overview

Below is a review of the gene therapy development landscape and exploration of marketed agents.

Investigational New Drug Applications For Gene Therapies Are Increasing in the US

  • Prior to clinical testing in human subjects, an IND application is submitted to the FDA for authorization to administer an investigational drug to humans1
  • The number of IND applications for gene therapy products submitted to the FDA has been steadily increasing since 2011, with an all-time high achieved in 20181

All New IND Applications for Gene Therapy Products by Year1,2

POGT-CDAAOGT-Slide3 2b

*Data adapted with permission from Lorrie McNeill, Director, FDA Office of Communications. Data in graph are from Marks 20182, except 2018 data from Eisenman 20191.
FDA, U.S. Food and Drug Administration; IND, investigational new drug.

There is a surge of gene and cell therapy products reaching the early development stage3

The FDA attributes this surge to the advent of safe and effective vectors for the delivery of genetic material, e.g. adeno-associated virus3

0
gene therapy trials are currently listed as active in the ClinicalTrials.gov database*4

The FDA predicts3

By 2020
>0
new INDs per year
By 2025
100
gene and cell therapy approvals per year
…and they plan to expand the team responsible for gene and cell therapies3
0
new clinical
 reviewers

Increasing Numbers of Gene Therapy Clinical Trials Are Being Approved Each Year

As of December 2018, just over 2900 gene therapy clinical trials have been completed or are ongoing worldwide5

Number of Gene Therapy Clinical Trials Approved Each Year Worldwide, 1989–20186

POGT-CDAAOGT-Slide5 2b

Figure adapted from The Journal of Gene Medicine, © 2017 John Wiley and Sons Ltd. Gene Therapy Clinical Trials Worldwide, December 2018. Available at: https://www.abedia.com/wiley/years.php. Accessed September 17, 2019.

Gene Therapy Clinical Trials Span Across All Development Phases

The proportion of trials in Phase 2–3 is rising5,7

  • Although the majority of gene therapy clinical trials to date have been in Phase 1, the percentages that are in Phase 2, Phase 2/3, and Phase 3 have increased from 15% in 2004 to 21.7% in 20185,7
  • This indicates progress in the prospect of bringing gene therapy to routine clinical practice7
POGT-CDAAOGT-Slide6 2

Phases of Gene Therapy Clinical Trials5

Figure reproduced from The Journal of Gene Medicine, © 2017 John Wiley and Sons Ltd. Gene Therapy Clinical Trials Worldwide, December 2018.
Available at: https://www.abedia.com/wiley/phases.php. Accessed September 17, 2019.

Many Diseases Are Promising Targets for Gene Therapy

Much of the previous research into gene therapy has focused on cancer and monogenic diseases8

  • Improved understanding of the genetics of inherited diseases is increasingly prompting research into gene therapy applications in a broader range of disorders8
  • Clinical trials of gene therapy for infectious diseases, cardiovascular disease, neurological diseases, and inflammatory diseases are ongoing7,9
POGT-CDAAOGT-Slide7 2

Indications Addressed by Gene Therapy Clinical Trials9

Figure reproduced from The Journal of Gene Medicine, © 2017 John Wiley and Sons Ltd. Gene Therapy Clinical Trials Worldwide, December 2018. Available at: https://www.abedia.com/wiley/indications.php. Accessed September 17, 2019.

Summary/Module Recap

  • There is an increasing number of gene therapies in the early stages of clinical development, including rising numbers in Phase 35,7

  • The FDA attributes this surge in gene therapies to the development of safer and effective vectors3

  • Consequently, approvals of gene therapies are expected to increase over the coming years3

  • Cancer and monogenic diseases have been the primary targets of gene therapy, but its use is now being explored in a diverse range of diseases7

  • A number of different agents have been approved by regulatory agencies for indications such as cancer and genetic diseases10,11,12,13,14,15

 

  1. Eisenman D. Applied Biosafety: J ABSA International 2019;24(3):147–152.
  2. Marks P. Presented at CASSS Cell & Gene Therapy Symposium 2018, Rockville, MD, USA.
  3. U.S. FDA. Press announcement. January 15, 2019. Available at: https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm629493.htm. Accessed September 17, 2019.
  4. ClinicalTrials.gov. Search term results. Available at: https://bit.ly/2UVsFXM. Accessed September 17, 2019.
  5. 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.
  6. The Journal of Gene Medicine. Gene Therapy Clinical Trials Worldwide, December 2018. Available at: https://www.abedia.com/wiley/years.php. Accessed September 17, 2019.
  7. Ginn SL, et al. J Gene Med 2018;20(5):e3015.
  8. Beitelshees M, et al. Discov Med 2017;24(134):313–322.
  9. The Journal of Gene Medicine. Gene Therapy Clinical Trials Worldwide, August 2018. Available at: https://www.abedia.com/wiley/indications.php. Accessed September 17, 2019.
  10. European Commission. Zynteglo. Available at: https://ec.europa.eu/health/documents/community-register/html/h1367.htm. Accessed September 17, 2019.
  11. European Commission. Strimvelis. Available at: https://ec.europa.eu/health/documents/community-register/html/h1097.htm. Accessed September 17, 2019.
  12. Yescarta® [package insert]. 2017. Available at: https://www.yescarta.com/files/yescarta-pi.pdf. Accessed September 17, 2019.
  13. 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.
  14. 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.
  15. Luxturna™ [package insert]. 2017. Available at: https://sparktx.com/LUXTURNA_US_Prescribing_Information.pdf. Accessed September 17, 2019.

 

  1. Eisenman D. Applied Biosafety: J ABSA International 2019;24(3):147–152.
  2. Marks P. Presented at CASSS Cell & Gene Therapy Symposium 2018, Rockville, MD, USA.
  3. U.S. FDA. Press announcement. January 15, 2019. Available at: https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm629493.htm. Accessed September 17, 2019.
  4. ClinicalTrials.gov. Search term results. Available at: https://bit.ly/2UVsFXM. Accessed September 17, 2019.
  5. 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.
  6. The Journal of Gene Medicine. Gene Therapy Clinical Trials Worldwide, December 2018. Available at: https://www.abedia.com/wiley/years.php. Accessed September 17, 2019.
  7. Ginn SL, et al. J Gene Med 2018;20(5):e3015.
  8. Beitelshees M, et al. Discov Med 2017;24(134):313–322.
  9. The Journal of Gene Medicine. Gene Therapy Clinical Trials Worldwide, August 2018. Available at: https://www.abedia.com/wiley/indications.php. Accessed September 17, 2019.
  10. European Commission. Zynteglo. Available at: https://ec.europa.eu/health/documents/community-register/html/h1367.htm. Accessed September 17, 2019.
  11. European Commission. Strimvelis. Available at: https://ec.europa.eu/health/documents/community-register/html/h1097.htm. Accessed September 17, 2019.
  12. Yescarta® [package insert]. 2017. Available at: https://www.yescarta.com/files/yescarta-pi.pdf. Accessed September 17, 2019.
  13. 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.
  14. 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.
  15. Luxturna™ [package insert]. 2017. Available at: https://sparktx.com/LUXTURNA_US_Prescribing_Information.pdf. Accessed September 17, 2019.