The FDA defines gene therapy as genetic material (virus plus therapeutic ‘transgene’). When such genetic material is administered to the body it can produce, modify or manipulate gene expression or alter the biological properties of living cells for therapeutic benefit for treating or curing a disease/disorder. Gene therapies are eligible to undergo other expedited regulatory pathways such as Priority Review or Breakthrough Therapy designation.
Globally, as of March 2021 there were over 2,400 gene therapy drug candidates in development. There are about 1,360 gene therapy programs at the preclinical stage and about 30 programs in Phase 1 clinical trials. Approximately 280 therapeutic candidates were in Phase 2 and 15 in Phase 3 development. Viral delivery vectors include retrovirus, lentivirus, adenovirus, adeno-associated virus (AAV), and herpes simplex virus (HSV).
There were 15 gene therapies marketed between 2003 and 2020. Three of these were AAV, two were adenovirus, four retroviral, two lentiviral, one was HSV, and three were naked DNA plasmids or lacked a viral vector. In terms of geographic spread there are more gene therapies approved or launched (seven) across Europe (EMA) than in any other region. In Asia, six therapies are available, but many were approved several years before the first gene therapies approvals in more heavily regulated markets such as the US and EU.
In the US, approved gene therapies include: Imlygicä in 2015 (first FDA approved gene therapy delivered with HSV to treat certain forms of cancer); Luxturna 2017ä (FDA approved AAV to treat mutation-associated retinal dystrophy); and Zolgensmaä in 2019 (FDA approved AAV to treat inherited spinal muscular atrophy); Zynteglo / LentiGlobin 2020 (FDA approved lentivirus to treat beta thalassemia); and Libmeldy 2020 (FDA approved lentivirus to treat metachomatic leukodystrophy).