Orphan legislations over the past thirty years have successfully increased the number of drugs receiving marketing authorization for rare diseases. However, for a therapy to be accessible to most patients, it requires not only marketing authorization, but market access via public reimbursement. In many major markets, the pricing and reimbursement of new therapies is based on an assessment by a national Health Technology Assessment (HTA) body, for which economic value is typically a key consideration. This research evaluates the outcome of HTAs of orphan drugs in Europe.

HTA decision data (to 31/08/2017) was extracted from Gemeinsame Bundesausschuss (G-BA), Haute Autorité de Santé (HAS), National Institute for Health and Care Excellence (NICE), Pharmaceutical Benefits Advisory Committee (PBAC), and Scottish Medicines Consortium (SMC) websites. EC-approval data was extracted from the European Medicines Agency (to 31/08/2017).

Only a small minority of drugs for orphan diseases received full recommendations for their licensed indication(s) by NICE (3/35, 9%), SMC (8/66, 12%) and PBAC (1/44, 2%). 37% (26/70) of drugs assessed received positive HTA outcome by HAS (ASMR I-III). In Germany, all approved orphan drugs (100/100) received automatic additional benefit post regulatory approval by G-BA.

There have been significant challenges for manufacturers in converting regulatory approval of orphan drugs into commercial success and optimised market access. Attaining positive HTA appraisals for these drugs, which have been approved under expedited regulatory pathways on a less than fully mature dataset, whilst also having high prices, due to small patient populations, limiting commercial returns, may necessitate increased utilisation of alternative reimbursement mechanisms.