EMA anticancer drug approval recommendations in 2015
21 January 2016, Nadina Grosios, Director Consultancy
In 2015, the European Medicines Agency (EMA) made a total of 93 positive recommendations to the European Commission for medicines to receive marketing approval; 39 of which concerned new active substances. Approximately one third of these new active substances were for the treatment of cancer. Furthermore, it would be no news to highlight that in 2015 the European regulatory arena of cancer therapies (and beyond) was dominated by immunotherapies.
Not only in the form of checkpoint inhibitors, which were approved in Europe in two different tumour types - melanoma (Opdivo (nivolumab) and Keytruda (pembrolizumab)) and non-small cell lung cancer (Opdivo) - but also with products such as Imlygic (talimogene laherparepvec, or “T-VEC”), a genetically modified herpes simplex virus type 1 designed to replicate within tumours and produce granulocyte-macrophage colony-stimulating factor (GM-CSF), an immunostimulatory protein in itself. In October 2015, Imlygic was the first oncolytic virus worldwide recommended for approval by the EMA and later that month it was approved by the US Food and Drug Administration (FDA) (Table 1, see below).
Passive immunotherapies also continued to be present. Blincyto (blinatumomab), a bispecific antibody targeting CD3 on T cells and CD19 on B cells, and Unituxin (dinutuximab), a GD2 glycolipid antibody, were both approved for the treatment of adult Philadelphia chromosome-negative acute lymphoblastic leukaemia (ALL) and high-risk neuroblastoma in children, respectively. The former received a conditional approval. The ALK kinase inhibitor Zykadia (ceritinib) was the second product to be conditionally approved. Both Blincyto and Zykadia are two of the seven products to have previously received an Orphan Drug Designation (ODD).
Even in terms of negative outcomes, Lympreva (dasiprotimut-T), an autologous vaccine containing tumour-specific idiotype proteins from individual patient's lymphoma cells and conjugated to keyhole limpet hemocyanin, was the only new anticancer entity to receive a negative opinion by the EMA in April 2015. EMA recommended the refusal of the marketing authorisation in relation to the treatment of patients with follicular non-Hodgkin’s lymphoma.
In terms of generic products for anticancer therapy, in 2015 there have been 9 products for which the EMA has given a recommendation for approval and interestingly 7 of those are for the generic Alimta (pemetrexed), a chemotherapy used for the treatment of pleural mesothelioma and NSCLC.
In 2015, the EMA also adopted a positive opinion and made recommendations with regards to approval in a new indication for an additional 10 anticancer medicines (already previously approved active substances; Table 2, see below). Most notable, the HER2 targeting monoclonal antibody Perjeta (pertuzumab) has now moved into neo-adjuvant breast cancer (in combination with trastuzumab and chemotherapy), the ALK/ ROS1 inhibitor Xalkori (crizotinib) into first line treatment for ALK-positive advanced NSCLC, and the Bruton's tyrosine kinase (BTK) covalent inhibitor Ibruvica (Ibrutinib), into first line treatment for Mantel cell lymphoma. Also the double combination of Mekinist (trametinib) and Tafinlar (dabrafenib) in BRAF V600 mutated melanoma were approved.
A glance over the EMA recommendations and EU approvals over the last 5 years shows that the overall number of anticancer medicines being considered and subsequently approved has increased; with immunotherapies, including both passive and active modalities, having steadily increased in numbers (Figure 1). Nevertheless, small molecule tyrosine kinase inhibitors (TKIs) are still adequately represented owing to second and third generation molecules targeting resistance. The number of “other” products comprising of Hedgehog pathway, proteosome inhibitors and epigenetic modulators is also increasing.
It would be a surprise if existing and newer immunotherapies such as for example PD-L1 antibodies and other check-point inhibitors and various formats of immune-based cell therapies did not continue to be in the regulatory spotlight in 2016. Nevertheless, there is still space for other types of therapies and for improving patient lives.