Number of new orphan-drug recommendations by the EMA rises to 18 in 2015

Details of orphan-medicine approvals in 2015 were contained in the European Medicines Agency (EMA)'s annual overview of its key recommendations (available to view here). The report reveals that the EMA issued a record number of orphan-drug approvals, with 18 of a total of 39 new recommended medicines being orphan-designated (46%). This compares to 17 orphan-designated medicines in 2014, and also marks a significant increase from the 11 recommended orphan-designated products in 2013. The number of orphan-medicine approvals is somewhat behind the rate of US FDA approvals, with the US agency announcing in January 2016 that 21 orphan drugs had been given regulatory clearance during 2015. Among the EMA's 2015 highlights for orphan medicines were new rare-cancer treatments, including Blincyto (blinatumomab; Amgen, US) to treat acute lymphoblastic leukaemia; Farydak (panobinostat; Novartis, Switzerland), a first–in-class histone deacetylase inhibitor for adult patients with relapsed or refractory multiple myeloma; and Amgen's multiple myeloma drug Kyprolis (carfilzomib).

The report highlights the increased use of special regulatory pathways for medicine approvals. On the basis of unmet medical need, early-access routes – subject to conditional market authorisation – were granted to Blincyto, Tagrisso (osimertinib; AstraZeneca, UK) for non-small-cell lung cancer (NSCLC), and Zykadia (ceritinib; Novartis) for treating anaplastic lymphoma kinase (ALK)-positive advanced NSCLC. Approval under exceptional circumstances was also provided for three medicines – Obizur (antihaemophilic factor [recombinant], porcine sequence; Baxalta, US) for patients with haemophilia; Raxone (idebenone; Santhera, Switzerland) for patients with the rare heritable genetic condition Leber's hereditary optic neuropathy (LHON); and Strensiq for childhood hypophosphatasia. Authorisations under exceptional circumstances are granted where comprehensive treatment data are not available, usually because the disease target is too rare or the collection of efficacy and safety data would be unethical. Special regulatory authorisations under both exceptional circumstances and conditional market authorisation are subject to stringent post-market-authorisation monitoring.

The increase in the number of orphan-designated medicines approved in 2015 is a generally encouraging development for the innovative pharmaceutical sector. However, in mid-2015, the EMA disclosed that there had been an overall decline in the amount of orphan-designated applications recorded in the first half of that year (see Europe: 12 October 2015: EMA reports decline in orphan-designated drug applications in H1 2015). Indeed, the EMA reported that orphan-designated applications totalled 120 between January and June 2015, compared with the 138 applications that were accepted in the same period of 2014. Meanwhile, the EMA forecast that it would receive an estimated 240 orphan-medicine applications for 2015 as a whole. If confirmed, this would mark a 20%-decline on 2014 figures. For the year ahead, new medicine approvals are likely to remain high; however, it is unclear whether the current rate of orphan-drug approvals can be maintained in light of the slightly lower number of submissions reported in the first half of 2015. A consequence of the lower number of filings is the possibility of fewer new-drug approvals in 2016 for diseases afflicting very small numbers of patients in the European Union – for which treatment options are severely limited. Elsewhere, the EMA reported encouraging findings that showed the application success rate for orphan-drug designations in the European Union in 2015 had risen to about 67% of cases (see Europe: 19 November 2015: EMA's COMP reports 67% approval rate for orphan-medicine designations in 2015).

Orphan-drug status in the European Union is granted to compounds developed for the treatment of rare diseases that occur in a maximum of 5 in 10,000 people. Upon receiving a final decision from the European Commission for market authorisation, orphan-drug manufacturers gain a 10-year period of patent protection. Market exclusivity can be extended by two years for paediatric approval. In addition, a number of incentives – including a reduction in fees and scientific advice through the Committee for Medicinal Products for Human Use – are provided with the designation.

Outlook and implications

The continued increase in the number of recommended orphan-designated medicines is encouraging for innovative pharmaceutical companies in Europe, which will benefit from incentives for rare-drug initiatives and high treatment prices. In addition, the industry will welcome the increased use of special regulatory pathways to market authorisation. The use of expedited review procedures for new medicines is also a positive development. However, only about 13% of the new medicines (5 out of 39 novel drugs – including Kanuma, Kyprolis and Lenvima) approved actually underwent assessments in Europe. This leaves substantial room for improvement – especially when compared to the US FDA, which expedited approvals for 27 out of 45 novel drugs in 2015 (including designated fast-track and breakthrough status, priority review, and accelerated approval provisions).