Intended for healthcare professionals

Observations Border Crossing

Orphan diseases: which ones do we adopt?

BMJ 2008; 337 doi: https://doi.org/10.1136/bmj.a1225 (Published 11 August 2008) Cite this as: BMJ 2008;337:a1225

Re: Orphan diseases: which ones do we adopt?

High prices of orphan medicines as compared to other medicines are a cause for concern as they put pressure on pharmaceutical budgets, may negatively influence patient access to pharmacotherapy, and may incite manufacturers to create monopolistic market conditions by splitting up a disease into several rare diseases.1 Even though high prices of some orphan medicines may be justified by high costs of research and development that need to be recouped from a small number of patients,2 orphan medicine pricing can be questioned in specific cases.

One such case is repurposing, i.e. the practice where a medicine for a common disease (e.g. ibuprofen for inflammatory joint disorders) is later shown to be effective in treating a rare disease (e.g. patent ductus arteriosis).3;4 As a result, the costs of research and development and the costs of market access of a repurposed medicine for a rare indication are expected to be lower than for a new medicine. This is particularly the case when evidence of the effectiveness of the medicine for the rare indication was published in the literature prior to the application for orphan designation. While repurposing – especially for rare diseases –is a very attractive strategy to overcome the logistical and financial burden of the first phases of medicine development (e.g. safety studies often can be skipped) and is advocated in public initiatives,5 we argue that repurposed medicines for rare indications for which effectiveness evidence has already been published do not warrant high prices.

The aim of this Letter is to identify examples of repurposed medicines for rare indications for which effectiveness evidence was published prior to the application for orphan designation and to compare Belgian prices between the common disease and the rare indication of the same medicine. We collected data on the trade name, defined daily dose (or the dose per capsule or per injection in the absence of a defined daily dose), pharmaceutical form and hospital price of the medicine for the common disease and of the repurposed medicine for the rare indication. Additionally, the year in which evidence of the effectiveness of the medicine for the rare indication was first published in the international literature and the year of orphan designation by the European Medicines Agency are reported.6

Table 1A compares Belgian hospital prices per defined daily dose of selected medicines for common diseases that were subsequently repurposed for rare indications. In the majority of cases, the pharmaceutical form of the medicine was identical for the common and for the rare indication. Medicine prices for the rare indication were nearly the same as for the common disease for cladribine and tadalafil, and ranged from a two-fold difference (e.g. aztreonam, sildenafil) to a 200-fold difference for histamine. Table 1A also includes three medicines that had a different pharmaceutical form for the rare indication: medicines for the rare indication were at least 56 times more expensive than for the common disease. Table 1B shows that hospital prices per dose for the rare indication were at least 23 times higher than for the common disease. Finally, evidence supporting the effectiveness of the medicine for the rare indication was published on average 13 years prior to the application for orphan designation.

We argue that price increases are not warranted for existing medicines which have been repurposed for a rare indication and for which effectiveness evidence was published in the literature prior to the application for an orphan designation, thereby minimising costs of research and development and costs of market access. Although a change in pharmaceutical form between the common disease and the rare indication may justify a price increase, the higher costs of research and development and of market access are unlikely to fully account for the observed price differences between the common disease and the rare indication.

Drawbacks of our study are that our results apply only to selected medicines that were repurposed for a rare indication and for which evidence of effectiveness was previously published in the literature, implying that our results cannot be generalised to all orphan medicines. Also, hospital prices of medicines pertained to Belgium and, thus, observed medicine price differences between the common disease and the rare indication may not be representative of price differences in other countries. However, researchers in other countries have also questioned the high prices of some orphan medicines and have emphasised the necessity to revisit orphan medicine pricing policies.7

In conclusion, this study suggests that the majority of these selected repurposed medicines for rare indications are over-priced in Belgium. This pricing practice is not justified and adds to the budget impact of treating rare diseases. Therefore, there is a need to individually assess repurposed medicines taking into account the costs of research and development and the costs of market access that can be attributed to the medicine for the rare indication as distinct from the costs of the medicine for the common disease.

References

(1) Schey C, Milanova T, Hutchings A. Estimating the budget impact of orphan medicines in Europe: 2. Orphanet J Rare Dis 2011; 6:62.
(2) Simoens S. Pricing and reimbursement of orphan drugs: the need for more transparency. Orphanet J Rare Dis 2011; 6:42.
(3) Ekins S, Williams AJ, Krasowski MD, Freundlich JS. In silico repositioning of approved drugs for rare and neglected diseases. Drug Discov Today 2011; 16(7-8):298-310.
(4) Food and Drug Administration. The Rare Disease Repurposing Database (RDRD). Food and Drug Administration [ 2011 [cited 2011 Nov. 10]; Available from: URL:http://www.fda.gov/ForIndustry/DevelopingProductsforRareDiseasesConditio...
(5) National Institutes of Health. The NIH Clinical Collections. National Institutes of Health [ 2011 [cited 2011 Nov. 9]; Available from: URL:http://www.nihclinicalcollection.com/index.php
(6) European Commission. Register of orphan medicinal products. European Commission [ 2011 [cited 2011 Nov. 8]; Available from: URL:PrFont34Bin0BinSub0Frac0Def1Margin0Margin0Jc1Indent1440Lim0Lim1http://ec.europa.eu/health/documents/community-register/html/orphreg.htm
(7) McCabe C, Stafinski T, Menon D. Is it time to revisit orphan drug policies? BMJ 2010; 341:c4777.

Competing interests: No competing interests

04 January 2012
Steven Simoens
Professor of Pharmacoeconomics
Eline Picavet, David Cassiman, Marc Dooms
Katholieke Universiteit Leuven
O&N2 bus 521, Herestraat 49, 3000 Leuven, Belgium