EMA & FDA Approvals and Recommendations in 2020 for Oncology Drugs and Diagnostics/Devices
January 18, 2021
Similar to previous years, 2020 also proved overall to be a successful year for drug approvals despite the COVID-19 pandemic. For the Food and Drug Administration (FDA), the number of approvals was higher than in 2019 (2020: 141 vs 2019: 131; Figure 1). A closer look at the EMA yearly positive recommendations shows a total of 97 in 2020 versus 126 in 2019 (Figure 1, see also EMA & FDA Oncology Approvals in 2019). The number of approvals observed with the FDA can be explained by the substantial increase in approvals of anti-cancer medicines and diagnostics/devices in 2020 as compared to 2019 (2020: 78 vs 2019: 36) and partly due to technological enhancements facilitating the application and approval process (e.g. eCTD developments). Despite the overall increase in positive recommendations/ approvals of anti-cancer medicines and diagnostics/devices (2020: 87 vs 2019: 57), the EMA issued a lower number of positive recommendations in 2020 (2020: 97 vs 2019: 126).
The numbers of immunotherapeutics and chemotherapeutics positively recommended/approved in 2020 by both agencies combined substantially increased as compared with previous years (2020: 35 and 17; 2019: 16 and 7; 2018: 18 and 6). Approvals/recommendations issued by both FDA and EMA in 2020 for immunotherapeutics and chemotherapeutics (Figure 2) include:
- Bavencio® (avelumab, Merck) for locally advanced/metastatic urothelial carcinoma;
- Blenrep® (belantamab mafodotin-blmf, GSK) for multiple myeloma;
- Keytruda® (pembrolizumab, Merck) for first-line treatment of MSI-H/dMMR colorectal cancer;
- Opdivo® (nivolumab, BMS) for recurrent/metastatic esophageal squamous cell carcinoma;
- Opdivo® and Yervoy® (nivolumab and ipilimumab, BMS) for first-line treatment of patients with metastatic/recurrent non-small cell lung cancer (NSCLC);
- Phesgo® (pertuzumab, trastuzumab, and hyaluronidase-zzxf, Genentech) for HER2-positive breast cancer;
- Reblozyl® (luspatercept-aamt, Celgene Corporation) for anemia in adults with myelodysplastic syndrome;
- Sarclisa® (isatuximab-irfc, Sanofi Aventis), combined with pomalidomide and dexamethasone, for multiple myeloma;
- Tecentriq® (atezolizumab, Genentech), in combination with bevacizumab, for unresectable/metastatic hepatocellular carcinoma.
While in 2019 the number of small molecules positively recommended/approved by both agencies substantially increased as compared to the previous year (2019: 33 vs 2018: 9), this trend was not maintained in 2020 (Figure 1; 31 small molecules).
- Alunbrig® (brigatinib, Ariad Pharmaceuticals) for ALK-positive metastatic NSCLC;
- Ayvakit® (avapritinib, Blueprint Medicines Corporation) for mutated gastrointestinal stromal tumors;
- Braftovi® (encorafenib, Array BioPharma) for metastatic colorectal cancer;
- Kyprolis® (carfilzomib, Onyx Pharmaceuticals) for relapsed/refractory multiple myeloma;
- Lynparza® (olaparib, AstraZeneca) for first-line maintenance treatment of advanced epithelial ovarian, fallopian tube, or primary peritoneal cancers;
- Retevmo® (selpercatinib, Eli Lilly) for metastatic RET fusion-positive NSCLC, advanced/metastatic RET-mutant and RET fusion-positive medullary thyroid cancer;
- Tukysa® (tucatinib, Seattle Genetics) combined with trastuzumab and capecitabine, for patients with advanced unresectable or metastatic HER2-positive breast cancer;
- Zejula® (niraparib, GSK) for first-line maintenance of advanced ovarian cancer.
Noteworthy, 2020 brought no approvals – from either the FDA or the EMA – of radiopharmaceuticals for oncology (Figure 2).
Keytruda® was approved for treatment of six new indications in Jan, Apr, Jun (3x), Oct, Nov (all FDA) and Dec (EMA)
Lynparza® was approved for treatment of three new indications in May (2x by FDA and 1x by EMA) and Sept (EMA)
The combination of Opdivo® and Yervoy® was approved for treatment of fur new indications in Mar, May (2x), Oct (all FDA) and Sep (EMA)
Tecentriq® was approved for treatment of three new indications in May (2x), Jul (all FDA) and Sep (EMA)
Venclexta® was approved for treatment of two new indications in Jan (EMA) and Oct (FDA)
While in 2019 there were in total 3 approvals of diagnostic agents/assays to be used in cancer (all by the FDA) and none for devices with utility in cancer (EMA & FDA Oncology Approvals in 2019), 14 such approvals/positive recommendations were given in 2020 (Figure 2), 13 for diagnostics agents/assays (12 by the FDA and one by the EMA) and one for a device (by FDA), all listed below:
- CobasHPV® test (Roche) for quantitative identification of women at risk for cervical cancer;
- EZH2 mutation® test (Roche) as a companion diagnostic to tazemetostat therapy, for identifying mutations in follicular lymphoma;
- FoundationOne® (Foundation Medicine):
- CDx test, for selection of patients with cholangiocarcinoma (carrying an FGFR2 rearrangement/fusion) or mCRPC (carrying germline BRCA1/2 alterations); as companion diagnostic for: immunotherapies for metastatic NSCLC, pembrolizumab therapy of unresectable/metastatic solid tumors (with TMB-H) and larotrectinib therapy of solid tumors (carrying fusions in neurotrophic receptor tyrosine kinase 1, 2 or 3 genes);
- Liquid CDx test, as a companion diagnostic to rucaparib therapy, to identify BRCA1/2 mutations in metastatic castration-resistant prostate cancer;
- Gallium 68 PSMA-11® (Siemens Healthineers) for PET imaging of prostate-specific membrane antigen- positive lesions in men with prostate cancer;
- Guardant360 CDx® assay (Gudrant Health) as companion diagnostic to identify patients with epidermal growth factor receptor gene mutations in a deadly form of metastatic NSCLC;
- Methylthioninium chloride® (Cosmo Technologies) as diagnostic agent to enhance visualization of colorectal lesions in patients undergoing colonoscopy;
- Myriad myChoice CDx® (Myriad Genetic Laboratories) as companion diagnostic for olaparib therapy for homologous recombination repair gene-mutated metastatic castration-resistant prostate cancer
- Oncomine Dx Target (ODxT)® test (Life Technologies Corporation) as companion diagnostic for praseltinib therapy for metastatic RET fusion-positive NSCLC or RET-mutant thyroid cancers;
- PD-L1 IHC 22C3 pharmDx® (Dako North America) as companion diagnostic for selecting patients with TNBC for pembrolizumab therapy;
- PD-L1 IHC 28-8 pharmDx® (Agilent Technologies) as companion diagnostic for first-line nivolumab and ipilimumab treatment of metastatic NSCLC;
- VENTANA HER2® test (Roche) for detection of HER2 in breast cancer and as a companion diagnostic for trastuzumab therapy;
- Vysis ALK Break Apart FISH Probe Kit® (Abbott Molecular) as companion diagnostic for brigatinib therapy of ALK-positive metastatic NSCLC;
- Sonalleve MR-HIFU® system (Profound Medical) as device used for treatment of osteoid osteoma in the extremities.
In terms of anti-cancer orphan drug and new active substance designations, as well as accelerated approvals, 2020 registered higher numbers as compared with 2019 (Figure 3, see also EMA & FDA Oncology Approvals in 2019). Overall, there were 30 orphan drug, 40 new active substance and 21 accelerated approval designations in 2020 given by FDA and EMA combined. The following nine compounds received all three designations simultaneously from the FDA, EMA or both: Blenrep® (belantamab mafodotin-blmf, GSK) for multiple myeloma, Gavreto® (Praseltinib, Blueprint Medicines Corporation) for metastatic RET fusion-positive NSCLC, Monjuvi® (tafasitamab-cxix, MorphoSys) for diffuse large B-cell lymphoma, Retevmo® (selpercatinib, Eli Lilly) for metastatic RET fusion-positive NSCLC and advanced/metastatic RET-mutant and RET fusion-positive medullary thyroid cancer, Tabrecta® (capmatinib, Novartis) for metastatic NSCLC, Tazverik® (tazemetostat, Epizyme) for metastatic/locally advanced epithelioid sarcoma, Tecartus® (brexucabtagene autoleucel) for relapsed/refractory mantle cell lymphoma, Trodelvy® (sacituzumab govitecan-hziy, Immunomedics) for metastatic TNBC, and Zepzelca® (lurbinectedin, PharmaMar) for metastatic SCLC (Figure 4).
Similar to 2019, the majority of anti-cancer drugs were developed for the treatment of patients with hematological malignancies, followed by lung and breast cancers (Figures 3 and 4). Indications included primarily diseases that are difficult to treat or with few treatment options, including relapsed, refractory, chronic, advanced and metastatic cancers.
Noteworthy, in 2020, similarly to 2019, Keytruda® (pembrolizumab, Merck) received eight approvals/recommendations from the FDA and EMA for extending its therapeutic indications, closing the year with six new indications in total (Figures 2 and 4). In 2020, several other compounds also received multiple approvals and/or recommendations (Figure 2) – all listed below:
- Lynparza® (olaparib, AstraZeneca) – four approvals/recommendations and three new indications (first-line maintenance treatment of advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer; (suspected) deleterious germline/somatic HRR gene-mutated metastatic castration-resistant prostate cancer; maintenance treatment of metastatic adenocarcinoma of the pancreas with germline BRCA 1/2-mutations);
- Opdivo® and Yervoy® (nivolumab and ipilimumab, BMS) – five approvals/recommendations and four new indications (hepatocellular carcinoma; first-line treatment of metastatic/recurrent NSCLC with no EGFR/ALK genomic tumor aberrations; first-line mNSCLC with PD-L1 tumor expression ≥1%; unresectable malignant pleural mesothelioma);
- Tecentriq® (atezolizumab, Genentech) – four approvals/recommendations and three new indications (first-line treatment of mNSCLC with high PD-L1 expression; BRAF V600 unresectable or metastatic melanoma; unresectable or metastatic hepatocellular carcinoma);
- Venclexta® (venetoclax, Abbive and Genentech) – two approvals/recommendations and two new indications (untreated AML, previously untreated CLL).
The FDA approved 53 and the EMA issued 39 positive recommendations for new molecular entities and new therapeutic biological products in 2020, designations received by innovative products that have never been used in clinical practice and/or have a new and unique mechanism for treating a medical condition. These include 21 innovative anti-cancer therapies and diagnostics approved by the FDA and 15 recommended by the EMA, of which the following have not been addressed in the text and/or figures above:
- Orgovyx® (relugolix, Myovant Sciences), the first oral gonadotropin-releasing hormone antagonist, for the treatment of adult patients with advanced prostate cancers;
- Margenza® (margetuximab-cmkb, MacroGenics), a chimeric IgG monoclonal antibody, approved in combination with chemotherapy, for the treatment of adult patients with metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease;
- Inqovi® (oral combination of decitabne and cedazuridine, Astex Pharmaceuticals), for the treatment of adult patients with myelodysplastic syndromes, including untreated/previously treated/de novo/secondary MDS or with intermediate-1, intermediate-2, and high-risk International Prognostic Scoring System groups;
- Zepzelca® (lurbinectedin, Pharma Mar), a synthetic alkaloid analogue that received the combined designations of new active substance and orphan drug, as well as accelerated approval for the treatment of adult patients with metastatic SCLC with disease progression on/after platinum-based chemotherapy;
- Pemazyre® (pemigatinib, Incyte Corporation), a fibroblast growth factor receptor 2 (FGFR2) antagonist that received the orphan drug designation and accelerated approval for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with an FGFR2 fusion or other rearrangement as detected by the FoundationOne® CDX (Foundation Medicine) FDA-approved test;
- Koselugo® (selumetinib, AstraZeneca), a selective mitogen-activated protein kinase inhibitor that received the orphan drug designation and accelerated approval for the treatment of pediatric patients, 2 years of age and older, with neurofibromatosis type 1 who have symptomatic, inoperable plexiform neurofibromas.
Drug approvals/positive recommendations issued in 2020 that made advances in patient care across a broad range of cancers include:
- Onbevzi (bevacizumab, SamsungBioepis), a biosimilar of the humanized anti VEGF-A antibody Avastin (GenenTech) approved by the EMA for Treatment of carcinoma of the colon or rectum, breast cancer, non-small cell lung cancer, renal cell cancer, epithelial ovarian, fallopian tube or primary peritoneal cancer, and carcinoma of the cervix;
- Phelinnum (melphalan, Adienne), a generic hybrid medicine approved by the EMA for the treatment of certain hematological and other cancers and as reduced intensity conditioning treatment prior to allogeneic hematopoietic stem cell transplantation in hematological diseases in adults and children;
- Rozlytek (entrectinib, Roche), a selecrtive tyrosine kinase inhibitor of the tropomyosin receptor kinases A, B and C, the C-ros oncogene 1 (ROS1) and the anaplastic lymphoma kinase approved by the EMA for the treatment of patients whose solid tumors have a neurotrophic tyrosine receptor kinase gene fusion, or patients with ROS1-positive advanced NSCLC. This treatment is‘tissue-agnostic’, targeting tumors based on genetic changes rather than the tissue of origin;
- Ruxience (rituximab, Pfizer), a biosimilar of the chimeric anti-CD20 monoclonal antibody Rituxan (Genentech, Roche) approved by the EMA for the treatment of non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis and microscopic polyangiitis, and Pemphigus vulgaris;
- Zercepac (trastuzumab, Accord Healthcare), a biosimilar of the monoclonal antibody Herceptin (Genentech) approved by the EMA for the treatment of:
- Early breast cancer, as monotherapy after surgery, chemotherapy and radiotherapy;
- Locally advanced breast cancer, before surgery in combination with chemotherapy and as monotherapy after surgery;
- Metastatic breast cancer and gastric cancers, as monotherapy;
- Metastatic gastric cancer, in combination with cisplatin and capecitabine or fluorouracil.
2020 saw a high number of positive recommendations/approvals for anti-cancer therapies, including numerous mAbs, as well as a continued increasing trend regarding positive recommendations/approvals of small molecules. Many innovative treatments were developed for patients with metastatic, refractory or otherwise difficult-to-treat diseases, and are expected to provide benefit to patients with generally few treatment options. Furthermore, treatments able to target multiple cancers (e.g., Keytruda®, Lynparza®, Opdivo®, Yervoy®, Venclexta®) suggest a utility for broad therapies. The higher numbers of positive recommendations/approvals for orphan drugs and new active substances recorded in 2020 vs 2019, specifically for simultaneous granting of these designations, indicate that the agencies’ efforts for accelerated assessment are paying off. These continued efforts are broadening the anti-cancer armamentarium available to patients.