EMA anticancer drug recommendations for approval in 2017
23 January 2018, Julia Holland, Consultant & Kun Shi, Consultant
In 2017, the European Medicines Agency (EMA) made a total of 92 positive recommendations to the European Commission for medicines to receive marketing approval. Approximately one fourth (23/92) were aimed at cancer treatment, which almost doubled the amount of recommendations from 13 in the previous year (Figure 1). These cancer treatments included novel immunotherapies, small molecules and traditional chemotherapy-based products. Among these, there was only one diagnostic agent - Axumin (fluciclovine (18F)) - which is used for the detection of recurrent prostate cancer using positron emission tomography (PET) imaging.
15 out of 23 recommendations received a swift approval in 2017 with a total number approved cancer treatments reaching to 19 during this year (Figure 2). Four of 19 marketing authorizations were recommendations from 2016. The remaining eight positive recommendations are close to approval in the near future.
From these 19 authorizations, 16 received their first approval and the remaining three received their approval of extension (or additional approval to extend the indication) (Figure 3).
Figure 1. Timeline of CHMP Recommendations for First Approval of Oncology Medicines in 2017. Data extracted from CHMP: Agendas, minutes and highlights- www.ema.europa.eu/ema
Figure 2. Timeline of CHMP Approvals in 2017.
Data extracted from GlobalData and EMA website-www.ema.europa.eu/ema.
In terms of existing chemical entities, it is remarkable that eight biosimilar medicines were recommended for approval in 2017. Five were biosimilar of rituximab (Rixathon, Riximyo, Blitzima, Tuxella and Ritemvia) for the indication of non-hodgkin’s lymphoma; one was a biosimilar of bevacizumab (Mvasi) for treatment of colorectal cancer, breast cancer, non-small cell lung cancer, renal cell cancer, ovarian cancer, and cervical cancer; and two were biosimilars of trastuzumab (Ontruzant and Herzuma) indicated for metastatic breast cancer and metastatic gastric cancer.
Six products received recommendations for orphan drug designation in diverse cancer indications. Dinutuximab beta is a monoclonal antibody designed to recognize and attach to a structure called GD2 that is overexpressed on the surface of neuroblastoma cells, but not normal tissue. Besponsa is a humanized immunoglobulin class G subtype 4 (IgG4) antibody that specifically recognizes human CD22 and is recommended as monotherapy for the treatment of adults with relapsed or refractory CD22-positive B cell precursor acute lymphoblastic leukemia (ALL). Bavencio is recommended in treating merkel cell carcinoma. It is worth to notice, if bavencio get approved, it could be the first immunotherapy treatment indicated for this aggressive skin cancer in the EU. Lutathera, the very first registered Peptide Receptor Radionuclide Therapy (PRRT) was recommended (and received its approval in treating gastroenteropancreatic neuroendocrine tumors (GEP-NETs). With this approval, Advanced Accelerator Applications (AAA), the company where Lutathera is produced, has become the first theragnostic radiopharmaceutical company in the oncology market. A protein kinase inhibitor Rydapt was recommended for approval either in combination with standard daunorubicin and cytarabine induction and high dose cytarabine consolidation chemotherapy or as monotherapy. The former one will be used in adult patients with newly diagnosed acute myeloid leukemia (AML) who are FLT3 mutation, the latter will be used in adult patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM AHN), or mast cell leukemia (MCL). The last orphan drug designation was recommended to Zejula, a medicine use in ovarian cancer.
Jylamvo a hybrid medicine of the reference medicine Methotrexat Lederle, demonstrated comparable quality bioequivalency to methotrexate-containing drugs such as Methotrexat Lederle and Ebetrexat. It is recommended in maintenance treatment of acute lymphoblastic leukemia (ALL).
Two medicines were added to the options available for the treatment of patients with locally advanced or metastatic breast cancer. One (Fulvestrant Mylan), a generic of Faslodex, which has been authorized in the EU since 10 March 2004. Studies with Fulvestrant Mylan have demonstrated the satisfactory quality when compare with Faslodex. The second is the protein kinase inhibitor Kisquli, with ribociclib succinate as active compound, which selectively inhibits cyclin-dependent kinase (CDK) 4 and 6. CDK4 and 6 being part of multiple signaling pathways play key roles in mammalian cell proliferation.
Pemetrexed disodium and Glibine were another two generic medicines receiving recommendations. The former one for unresectable malignant pleural mesothelioma and locally advanced or metastatic non-small cell lung cancer and the latter for leukemia and gastrointestinal stromal tumors.
VEGF inhibitor Fotivda received recommendation in advanced renal cell carcinoma. It is the third protein kinase inhibitor this year.
Tecentriq, an immunotherapy developed by Roche, received recommendation as a monotherapy for the treatment of people with locally advanced or metastatic non-small cell lung cancer (NSCLC) after they have been previously treated with chemotherapy regardless of PD-L1 status.
Tookad works as vascular-acting photosensitizer and consisted active padeliporfin, received recommendation in treating men with low risk prostate cancer.
There were two products that the EMA has given a negative opinion in 2017 for anticancer therapy. Onzeald (etirinotecan pegol), a medicine used to treat breast cancer with metastases received a negative opinion in July 2017. Re-examination was requested, however the conclusion in November remained negative. In December, Aplidin (plitidepsin) from Pharma Mar SA, a medicine used to treat multiple myeloma in combination with dexamethasone, received a negative opinion for the approval of the marketing authorization application (MAA) from the Committee for Medicinal Products for Human Use (CHMP). Re-examination process by the European Medicines Agency (EMA) has been initiated and the outcome will be published/announced later of 2018.
In terms of withdrawal of applications, six out of 18 cancer treatments have been withdrawn. In which four (Qinprezo, Zafiride, Ogivri and Kyomarc) were withdrawn from their initial marketing authorizations and two (Opdivo and Keytruda) were withdrawals from extended use/indication.
There is no doubt that the increased number of recommendation of approvals and extensions will benefit more patients and their families. Regarding the pediatric medicines, there were several more recommendations on extension in pediatric patients in 2017. However, the numbers remain low for positive recommendations calling for improvement and innovation in this vulnerable patient population.
Figure 3: first approval vs Additional approval in 2017.
Figure 4: Medicines Class per Indication.
Table 1: Novel medicines recommended for first approval by the CHMP (EMA) in 2017
NHL: Non-Hodgkin's lymphoma
Table 2: Novel medicines approved by the CHMP (EMA) in 2017
* indicates an additional approval of the medicine. mAb: monoclonal antibody, ALL: Acute Lymphocytic Leukemia, AML: Acute Myelocytic Leukemia, BC: Breast Cancer, CLL: Chronic Lymphocytic Leukemia, FLT3: fms like tyrosine kinase 3, NHL: Non-Hodgkin Lymphoma, met.: metastatic, NSCLC: Non-Small-Cell-Lung-Cancer, OC: Ovarian Cancer, PARP: poly ADP ribose polymerase, PD-L1: Programmed death-ligand 1, RCC: Renal Cell Carcinoma, VEGF: Vascular endothelial growth factor
Table 3: Extension of indication for already approved oncology medicines.