TABLE I.
Gene Therapy Approvals Worldwide
| Indication | Vector (Delivery Method) |
Gene Product | Name | Jurisdiction | Year Approved |
|---|---|---|---|---|---|
| Head and neck cancer | Adenovirus (in vivo) | p53 | Gendicine (recombinant human p53 adenovirus) | People’s Republic of China | 2003 |
| Solid tumors | Retrovirus (in vivo) | Mutant cyclin G1 | Rexin-G | Philippines | 2007 |
| Peripheral artery disease | Plasmid (in vivo) | Vascular endothelial growth factor | Neovasculgen Cambiogeneplasmid | Russia | 2011 |
| Lipoprotein lipase deficiency | AAV (in vivo) | Lipoprotein lipase | Glybera (alipogene tiparvovec) | EMA | 2012 |
| Melanoma | Herpes simplex virus (in vivo) | Granulocyte-macrophage colony stimulating factor | Imlygic (talimogene laherparepvec) | FDA, EMA | 2015 |
| Adenosine deaminase deficiency | Retrovirus (ex vivo) | Adenosine deaminase | Strimvelis | EMA | 2016 |
| Restoration of host immune system | Retrovirus (ex vivo) | Low affinity nerve growth factor receptor | Zalmoxis* | EMA | 2016 |
| Osteoarthritis | Retrovirus (ex vivo) | Transforming growth factor-β | Invossa† (tonogenchoncel-L) | South Korea | 2017 |
| Acute lymphoblastic leukemia | Lentivirus (ex vivo) | Chimeric antigen receptor | Kymriah (tisagenlecleucel) | FDA, EMA | 2017, 2018 |
| Large B-cell lymphoma | Retrovirus (ex vivo) | Chimeric antigen receptor | Yescarta (axicabtagene ciloleucel) | FDA, EMA | 2017, 2018 |
| Biallelic RPE65 mutation-associated retinal dystrophy | AAV (in vivo) | Retinal pigment epithelium-specific 65 kDa protein | Luxturna (voretigene neparvovec-rzyl) | FDA, EMA | 2017, 2018 |
| Spinal muscular atrophy | AAV (in vivo) | Survival motor neuron-1 | Zolgensma (onasemnogene abeparvovec) | FDA | 2019 |
| β-thalassemia | Lentivirus (ex vivo) | β-globin | Zynteglo‡ (betibeglogene autotemcel) | EMA | 2019 |
| Critical limb ischemia | Plasmid (in vivo) | Hepatocyte growth factor | Collategene (beperminogene perplasmid) | Japan | 2019 |
| Multiple myeloma | Lentivirus (ex vivo) | Chimeric antigen receptor | Abecma (idecabtagene vicleucel) | FDA | 2021 |
Zalmoxis, comprising genetically modified allogeneic T cells, was conditionally approved by the EMA for the restoration of the host immune system after hematopoietic stem cell treatment pending the outcome of a Phase-III trial. This trial was suspended because an interim analysis suggested that the primary end point had not been met. The EMA withdrew Zalmoxis authorization in 2019.
Invossa was withdrawn in 2019. Phase-II trials have started in the U.S.
Zynteglo was conditionally approved for β-thalassemia pending additional clinical data. Its deployment is presently on hold because of 2 malignancies occurring in a related clinical trial of sickle cell anemia. Reproduced, with modification, from: Evans CH. The vicissitudes of gene therapy. Bone Joint Res. 2019 Nov 2;8(10):469-471. © The Authors under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (CC BY-NC-ND 4.0) license.