TABLE 2.
List of approved gene therapy medicinal products (GTMPs).
| No. | Trade name/proper name | Manufacturer | Indications | Approved by/date | Dosage | Product form | Description | AT/AL | Price |
| 1 | Kymriah Tisagenlecleucel (Miller, 2018; Food and Drug Administration, 2019k) | Novartis Pharmaceuticals, Corp. (United States) | Refractory B-ALL or in second or later relapse for patients up to 25 years of age | US FDA 2017 August | Intravenous administration of 0.2–5.0 × 106 cells/kg for ≤ 50 kg, and 0.1–2.5 × 108 cells/kg for > 50 kg B-cell ALL patients up to 25 years of age and 0.6–6.0 × 108 cells for adult r/r DLBCL | Bag | CD19-targeted genetically modified T-lymphocytes | AT | $475,000 for ALL and $373,000 for DLBCL |
| 2 | Yescarta Axicabtageneciloleucel (Clarke and Berkrot, 2019; Food and Drug Administration, 2019l) | Kite Pharma, Inc. (United States) | Adult patients with r/r large B-cell lymphoma after two or more lines of systemic therapy, including DLBCL not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma | US FDA 2017 October | 2 × 106 CAR-T cells/kg | Bag | CD19-targeted genetically modified T lymphocytes | AT | $373,000 per treatment |
| 3 | Zolgensma Onasemnogene abeparvovec-xioi (Food and Drug Administration, 2019m) | AveXis (United States) | Pediatric patients < 2 years of age with SMA and bi-allelic mutations in the SMN1 gene | US FDA 2019 May | 1.1 × 1014 to 1.4 × 1014 vg/kg | Vial | AAV9 vector containing functional copy of the SMN1 gene | - | $2.1 million per treatment |
| 4 | Kymriah Tisagenlecleucel (European Medicines Agency, 2019) | Novartis Pharmaceuticals, Corp. (United States) | Patients up to 25 years of age with refractory B-ALL, who are in relapse post-transplantation or in second or later relapse, and adult patients with r/r DLBCL after two or more lines of systemic therapy | EMA 2018 August | Intravenous administration of 0.2–5.0 × 106 cells/kg for ≤ 50 kg, and 0.1–2.5 × 108 cells/kg for > 50 kg B-cell ALL patients up to 25 years of age and 0.6–6.0 × 108 cells for adult r/r DLBCL | Bag | CD19- targeted genetically modified T-lymphocytes | AT | $475,000 for ALL, and $373,000 for DLBCL |
| 5 | Yescarta Axicabtagene ciloleucel (Clarke and Berkrot, 2019; Yeskarta) | Kite Pharma, Inc. (United States) | Adult patients with r/r DLBCL and PMBCL after 2 or more lines of systemic therapy | EMA 2018 August | 2 × 106 CAR-T cells/kg | Bag | CD19-targeted genetically modified T- lymphocytes | AT | $373,000 per treatment |
| 6 | Imlygic Talimogene laherparepvec [Imlygic, 2017; IMLYGIC (talimogene laherparepvec) | FDA, 2020] | Amgen, Inc. (United States) | Unresectable cutaneous, subcutaneous, and nodal lesions in recurrent melanoma after initial surgery | US FDA 2015 October | An initial dose of up to 4 × 106 PFU/ml, followed by subsequent doses of up to 4 ml at a concentration of 108 PFU/ml | Vial | Live, attenuated HSV-1 genetically modified to express hGM-CSF | - | $65,000 per treatment |
| EMA 2015 December | |||||||||
| 7 | Zalmoxis (Zalmoxis, 2016; MolMed, 2019) | Molmed S.p.A. (Italy) | Haploidentical-HSCT adult patients with high-risk hematological malignancies | EMA 2016 August Withdrawn 2019 October | 1 ± 0.2 × 107 cells/kg | Bag | Genetically modified T-lymphocyte with a retroviral vector encoding ΔLNGFR and HSV-TK | AL | $170,000 (Italy) $186,000 (Germany) |
| 8 | Strimvelis (Mullin, 2019; Stem Cell Research, 2019) | GlaxoSmithKline (GSK, United Kingdom) | ADA-SCID | EMA 2016 May | The recommended dose range is between 2 and 20 million CD34 + cells/kg | Bag | Transduced CD34 + cells with a retroviral vector encoding human ADA | AT | $648,000 per treatment |
| 9 | Luxturna Voretigeneparvovec-rzyl (Berkrot, 2018; Food and Drug Administration, 2019n) | Spark Therapeutics, Inc. (United States) | Biallelic RPE65 mutation-associated retinal dystrophy | US FDA 2017 December | Sub-retinal injection of 1.5 × 1011 AAV vector genomes in a total volume of 0.3 ml for each eye | Vial | Live, non-replicating AAV2 genetically modified to express hRPE65 gene | - | $425,000 per eye |
| EMA 2018 September | |||||||||
| 10 | Gendicine (Rosen, 2012; Sibiono, 2019) | Shenzhen SiBiono Gene Tech, Co., Ltd. (China) | Late-stage HNSCC or terminal-stage non-HNSCC tumors | CFDA 2003 October | Administration of 1–4 × 1012 VP once every 3–7 days over a course of 3–8 weeks | Vial | Recombinant adenovirus expressing human p53 | - | Up to $100,000 per dose |
| 11 | Oncorine (SunWay Biotech, 2019) | Shanghai Sunway Biotech (China) | Nasopharyngeal carcinoma | CFDA 2005 November | 5 × 1011 VP for 5 consecutive days | Vial | Recombinant human adenovirus type 5 with E1B-55kD and E3 region deletion | - | NA |
| 12 | Kymriah Tisagenlecleucel (Novartis., 2019b) | Novartis Pharmaceuticals Canada, Inc. (Canada) | 3–25 year old patients with refractory B-ALL, relapsed after allogeneic SCT or ineligible for SCT, or with second or later relapse, and adult patients with r/r large B-cell lymphoma after two or more lines of systemic therapy including DLBCL not otherwise specified, high grade B-cell lymphoma and DLBCL arising from follicular lymphoma | Health Canada 2018 September | Intravenous administration of 0.2–5.0 × 106 cells/kg for ≤50 kg, and 0.1–2.5 × 108 cells/kg for > 50 kg B-cell ALL patients up to 25 years of age and 0.6–6.0 × 108 cells for adult relapsed or refractory diffuse large B-cell lymphoma | Bag | CD19-targeted genetically modified T-lymphocytes | AT | $475,000 per treatment |
| 13 | Neovasculgen Cambiogeneplasmid (NOVARTIS, 2019a) | Human Stem Cells Institute (Russia) | PAD, including CLI caused by atherosclerosis | MOH of the Russia Federation 2011 December | 2 sequential injections (i.e., 2 vials) of 1.2 mg of pCMV- veg f165 with an interval of 14 days | Vial | Plasmid encoding the CMV-VEGF (165 aa) gene | - | ∼ $6600 per treatment |
| 14 | Zynteglo (ClinicalTrials, 2020) | bluebird bio (Netherlands) B.V. | Patients up to 12 years old with beta thalassemia who require regular blood transfusions | EMA 2019 May | 1.2–20 × 106 cells/mL dispersion for infusion | Bag | CD34 + cells encoding βA-T87Q-globin gene | AT | $1.78 million |
AAV, adeno-associated virus; ADA-SCID, adenosine deaminase severe combined immunoeficiency; AL, allogeneic; AT, autologous; B-ALL, B-cell precursor acute lymphoblastic leukemia; CAR, chimeric antigen receptor; CFDA, China Food and Drug Administration; CLI, critical limb ischemia; DLBCL, diffuse large B-cell lymphoma; EMA, European Medicines Agency; FDA, Food and Drug Administration; GM-CSF, granulocyte macrophage colony-stimulating factor; HNSCC, head and neck squamous cell carcinoma; hRPE65, human retinal pigment epithelium 65 kDa; HSCT, hematopoietic stem cell transplantation; HSV, herpes simplex virus; NA, not available; MOH, Ministry of Health; NGFR, nerve growth factor receptor; PAD, peripheral artery disease; PFU, plaque forming unit; PMBCL, primary mediastinal large B-cell lymphoma; r/r, relapsed or refractory; SMA, spinal muscular atrophy; SMN, survival motor neuron; VEGF, vascular endothelial growth factor; VG, vector genome; VP, viral particle. All prices are in USD.