Table 1 FDA approved epi-drug for cancer treatment
| Epi-drug | Development Overview | Characteristics | Mechanism of Action | Data of approval | Disease approval | Phase 3 | Phase 2 | Phase 1/2 | Most Recent Events |
|---|---|---|---|---|---|---|---|---|---|
| Vidaza | Clinical studies began in 1980s. However, in the first studies its activity had not been maximized as the mechanism had not yet been identified. In 2004 Azacitidine was marketed as Vidaza in the USA, in subcutaneous administration, for the treatment of five subtypes of MDS. In January 2007, the FDA approved the administration for intravenous use. Azacitidine is available in the EU and several Asia–Pacific countries for the treatment of high-risk MDS, AML, and CML, in Canada and Japan for MDS high risk and a subgroup of AML patients who are not eligible for stem cell transplantation. In September 2020 the drug was approved in oral administration (ONUREG), for AML patients in first complete remission or with complete remission but incomplete blood recovery after chemotherapy (NCT0175735) |
Antineoplastics; Aza compounds; Pyrimidine nucleosides |
Antimetabolites; DNMT inhibitors |
2004 for MDS 2020 for AML | MDS, AML and CML | TL | BC; Leukemia; NC; NSCLC; Peripheral TL | CC; Diffuse large B cell lymphoma; RC; Solid tumors |
25 May 2020 Preregistration for AML (First-line therapy) in European Union (PO) |
| Decitabine | Decitabine is developed by Otsuka and Janssen-Cilag for MDS and AML. The compound is used in the USA and many other countries outside the EU for MDS and in Malaysia for CML and AML in the EU. The product is also undergoing regulatory review in China for MDS and AML. Clinical development is ongoing for MDS and ovarian cancer. Decitabine has shown limited efficacy against solid tumors. A combined, orally bioavailable, fixed-dose formulation of decitabine plus cedazuridine was approved in 2020 for MDS |
Antineoplastics; Aza compounds; Deoxyribonucleosides; Pyrimidine nucleosides | DNMT inhibitors | 2006 for MDS | MDS, AML and CML | T-ALL, T-LBL, T/M-MPAL | Malignant melanoma; OC |
07 Dec 2019 Pharmacodynamics data from a preclinical study in acute myeloid leukemia | |
| Vorinostat | Vorinostat has been launched in the USA, Canada, Japan, Argentina, Chile, and Greece for CTCL treatment. Development of vorinostat was discontinued in mesothelioma non-small cell lung cancer, gynecological cancer, and pancreatic cancer. Vorinostat was in phase II development for colorectal cancer and sickle-cell anemia. However, no development in these indications have been reported | Antineoplastic, hydroxamic acid | HDAC inhibitors | 2006 | CTLC | MM; MLC | AML; B-cell lymphoma; BC; Glioma; HIV-1; MDS; NHL; ALL | ALL; Lymphoma; Solid tumors |
09 Apr 2019 Merck & Co completes a phase II trial in B-cell lymphoma in South-East Asia (PO) (NCT00875056) |
| Romidepsin | Romidepsin developed by Celgene was discovered by Fujisawa Pharmaceutical from Chromobacterium violaceum. The intravenous formulation of romidepsin was tested in the USA for CTLC, PTCL. Clinical development is underway for breast cancer, multiple myeloma, T-cell leukemia, and T-cell lymphoma in several countries. In 2015 Romidepsin was in pre-registration phase for peripheral T-cell lymphoma and in phase II for cutaneous T-cell lymphoma, and studies for the treatment of renal cell carcinoma, prostate cancer, and pancreatic cancer were stopped | Antineoplastics; Cytostatic antibiotics; Depsipeptides | HDAC inhibitors | 2009 | CTLC, PTCL | BC; MM; T-LL |
11 Apr 2020 Celgene Corporation and University of California completes a phase I trial in Cutaneous T-cell lymphoma in the USA (NCT01902225) 25 Mar 2020 Celgene Corporation suspends a phase-I/II clinical trials in breast cancer (combination therapy) in the USA, due to five patients’ responses pending (NCT02393794) | ||
| Belinostat | Belinostat is developed by Onxeo and Spectrum Pharmaceuticals. Intravenous belinostat is available in the USA and is under regulatory review in Canada as a monotherapy for PTCL. Clinical trial is ongoing for B-cell lymphoma and glioblastoma, in the USA, and for NSCLC in the USA and Denmark. Development for the treatment of multiple myeloma has been stopped | Acrylamides; Antineoplastics; Hydroxamic acids | HDAC inhibitors | 2014 | PTCL | B-cell lymphoma; Glioblastoma | NSCLC |
10 Apr 2020 National Cancer Institute plans a phase II trial for Chondrosarcoma (Combination therapy, second-line therapy or greater) (NCT04340843) | |
| Panobinostat | Panobinostat being developed by Novartis and Secura Bio, for the treatment of cancer and HIV infections, and after approved from the FDA in 2015 for MM | Antineoplastic, hydroxamic acid | HDAC inhibitors | 2015 | MM | CMML | AML; CLL; CC; Lymphoma; MDS; Myelofibrosis; Neuroendocrine tumors; NHL; T-LBL; RC; TC | BC; HIV-1; Hodgkin’s disease; melanoma |
11 Aug 2020 Phase-I clinical trials in Glioma (In children, In adults, Combination therapy, Second-line therapy or greater) in the USA (PO) (NCT04341311) 22 Jun 2020 Phase I development is ongoing for Myelofibrosis (combination therapy) in Germany, France, UK, Ireland and Italy (NCT01433445) |
| Ivosidenib | Ivosidenib was approved on July 20, 2018, in oral administration, for adult patients with relapsed or refractory AML with IDH1 mutation. From May 2019, the drug was approved also for newly diagnosed AML with a susceptible IDH1 mutation in patients who are at least 75 years old or that cannot be treated with chemotherapy (NCT0274839) | Antineoplastics; Cyclobutanes; Pyridines; Pyrrolidines | IDH1 inhibitors | 2018 | AML with IDH1 mutation | Cholangiocarcinoma; MDS |
30 Jul 2020 Agios pharmaceuticals announces to submit sNDA to US FDA for Cholangiocarcinoma, in second-line therapy in the 2021 | ||
| Enasidenib |
In August 2017, Enasidenib (IDHIFA®), produced by Celgene, was approved from the FDA for the treatment of adult patients with relapsed or refractory AML with IDH2 mutation. The drug is used first for AML in the USA and then approved in Australia. Clinical developments are ongoing for AML, solid tumors, CML, and MDS Other potential indications include a genetic neurometabolic disorder (Type II D-2-HGA; 2-Hydroxyglutaricaciduria) | Amines; Antineoplastics; Pyridines; Triazines | IDH2 inhibitors | 2017 | AML with IDH2 mutation | MDS | Solid tumor |
12 Jun 2020 Celgene reinitiates a phase II trial in adult patients AML as second-line therapy in the USA (PO) (NCT03881735) | |
| Tazemetostat |
Tazemetostat, developed by Epizyme in orally administration, is used for MES and FL treatment in the USA. Clinical development of the oral formulation is ongoing for B-cell lymphoma, central nervous system cancer, follicular lymphoma, histiocytosis, mesothelioma, non-Hodgkin’s lymphoma, non-small cell lung cancer, and solid tumors in the USA, Australia, Japan, Canada, and the European Union Eisai and Epizyme with Roche Molecular Systems are developing complementary diagnostics to help companies identify patients with lymphoma with EZH2 gene mutations, to be used in parallel with the clinical development of tazemetostat Clinical development of the suspension formulation of tazemetostat for the treatment of solid tumors was ongoing in the USA. However, as of September 2018, no recent development reports for the formulation have been identified | Antineoplastics; Biphenyl compounds; Dihydropyridines | Inhibitor of wild-type and mutated forms of EZH2 and SMARCA2 and SMARCA4 | 2020 | MES, FL | CNS cancer; DLBCL; Histiocytosis; OC; Mesothelioma; NHL; Peritoneal cancer; Rhabdoid tumor; Solid tumors; Synovial sarcoma; Uterine cancer | Bladder cancer; NSCLC; PC |
08 Jul 2020 Preregistration for FL (Refractory metastatic disease, Second-line therapy or greater) in Japan (PO) 22 Jun 2020 Pharmacodynamics data from a preclinical trial in NSCLC |