EMA anticancer drug approval in 2014
22 January 2015, Raymond Hoffmans, Chief Business Development Officer
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) approved 82 new drugs in 2014. About 10% of these are used to treat cancer (8 drugs). This is less then in 2013 when 19% of the approved new drugs were anticancer drugs. In addition to the approval of new drugs, the CHMP gave 39 positive opinions for an extension of therapeutics indications for previously approved drugs. Eight of these opinions were for an indication extension of approved anticancer drugs, including 5 for a modification within an existing indication and 3 for an extension into a new indication.
Similar to 2013, the majority of anticancer drugs that received an approval or an extension into a new indication were protein kinase inhibitors (6 drugs). The other drugs can be classified as monoclonal antibody (2 drugs), PARP inhibitor (1 drug), proteosome inhibitor (1 drug) or vinca alkaloid (1 drug).
New treatment options
Several new treatment options became available to hematologists to treat hematological malignancies this year. For chronic lymphocytic leukemia (CLL) three drugs were approved in 2014. Roche received approval for obinutuzumab (Gazyvaro), an anti-CD20 monoclonal antibody to be combined with chlorambucil to treat adult patients with previously untreated CLL who are not eligible for fludarabine based therapy. Ibrutinib (Imbruvica), a Bruton’s tyrosine kinase inhibitor from Janssen, and idelalisib (Zydelig), a PI3K kinase inhibitor from Gilead (to be combined with rituximab), have been approved for CLL in patients who have received at least one prior therapy or in patients with 17P deletion or TP53 mutation who are unsuitable for chemo-immunotherapy. In addition, idelalisib was approved for follicular lymphoma that is refractory to two prior treatment lines, and ibrutinib for refractory or relapsed mantle cell lymphoma. Another new treatment option for mantle cell lymphoma is the proteasome inhibitor bortezomib (Velcade) from Janssen. Bortezomib received a label extension to treat previously untreated mantle cell lymphoma in combination with rituximab, cyclophosphamide, doxorubicin and prednisone.
For ovarian cancer, two new drugs were approved. Olaparib (Lynparza), a PARP inhibitor from AstraZeneca, will be used to treat ovarian, fallopian tube and primary peritoneal cancer in women with BRCA mutations. Vinfatolide (Vynfinit), a vinca alkaloid from Endocyte, will be used in combination with pegylated liposomal doxorubicin for the treatment of adult patients with platinum resistant ovarian cancer who express the folate receptor on all target lesions.
Boehringer Ingelheim received approval for their nintedanib (Vargatef), a protein kinase inhibitor targeting VEGFR 1-3, FGFR 1-3 and PDGFR α and ß, for non-small cell lung cancer (NSCLC). Nintedanib is indicated in combination with docetaxel for the treatment of locally advanced, metastatic or locally recurrent non-small cell lung cancer (NSCLC) after first-line chemotherapy.
Other anticancer drug approvals in 2014 include ramucirumab (Cyramza), a VEGF binding monoclonal antibody from Eli Lilly, for gastric cancer and trametinib (Mekinist), a MEK inhibitor from GSK, for unresectable or metastatic melanoma with a BRAF V600 mutation. Interestingly, trametinib did not demonstrate clinical activity in patients who progressed on a prior BRAF inhibitor.
Bayer had label extensions for two drugs into new oncology indications. Regorafenib (Stivarga), a dual VEGF-R2 – TIE2 kinase inhibitor, was previously approved for colorectal cancer and can now also be used to treat patients with unresectable or metastatic gastrointestinal stromal tumors (GIST) who progressed or who are intolerant to prior treatment with imatinib and sunitinib. The label of sorafenib (Nexavar), a protein kinase inhibitor targeting VEGF-R, PDGF-R and Raf, has been extended to also include refractory thyroid carcinoma. Sorafenib was already approved for liver and kidney cancer.
The CHMP gave four negative recommendations for anticancer therapies in 2014. These include Masiviera (AB Science) for pancreatic cancer, Avastin (Roche) for glioblastoma multiforme, Javlor (Pierre Fabre) for breast cancer and Tasigna (Novartis) for CML in which imatinib did not lead to a complete molecular response.