A comparative study of orphan drug prices in Europe

Figures & data

Table 1. Orphan drugs (OD) HTA, pricing, reimbursement, and market access in major European countries.

Country	HTA specificities for ODs	Pricing of ODs	Reimbursement of ODs
France	Undergo the same HTA procedure as non ODs.[8]	Same pricing procedure as non ODs.[11]	Reimbursement through the standard process
	May benefit from a fast track assessment process reducing timelines from 90 days to 15 days.[10]	Price driven by improvement in actual benefit (IAB)/Amélioration du Service Médical Rendu (ASMR)	Driven by actual benefit (AB)/Service Médical Rendu (SMR) but more flexibility regarding the strength of supporting evidence in ODs.[10]
	Exemption for health economic evaluation applied to ODs with low budget impact (<€30 million/year for a particular indication).[11]	Usually high priced (ASMR I- III).[11]	Most ODs (98%) are reimbursed.[8]
		Almost all innovative drugs enter the French market as part of a price-volume agreement.[11]
Germany	For ODs authorised by EMA, benefit is considered proven with market authorisation. The G-BA only determines the extent of additional benefit (minor, considerable, major, or non-quantifiable), the categories ‘no additional benefit’ or ‘less benefit’ are not applicable.[12]	Same pricing procedure as non ODs.[11,12]	Reimbursement through the standard process. Full reimbursement for the first year following MA.[11,12]
	The initial assessment for ODs is based on the studies for market authorisation and not on a comparison over an appropriate comparator.[12]	Free pricing during the first year following MA, price is negotiated thereafter between the manufacturer and the Federal Association of Statutory Health Insurance Funds (GKV-SV) based on the added value of the OD decided by G-BA.[11,12]	Thereafter, reimbursement of negotiated price based on initial assessment if the revenue is less than €50million/year.[11,12]
	G-BA and IQWIG assessment criteria tend to be more flexible for ODs.[11]		If revenue is more than €50 million over the previous year, OD is subject to an additional benefit re-assessment vs. current standard of care/appropriate comparator.[11,12]
Italy	Undergo the same HTA procedure as non ODs	Same pricing procedure as non ODs but flexible regarding pricing regulations, clinical data requirements, level of clinical uncertainty, and higher price may be accepted.[8,11,13]	Reimbursement through the standard process
	Evaluated by the Italian Medicines Agency (AIFA) and regional HTAs.[8,11,13]	Price is negotiated between AIFA and the manufacturer, confidential discounts and rebates may also apply for ODs.[11]	Most ODs are distributed through hospital channel.[8,11]
Norway	Undergo the same HTA procedure as non ODs.[10]	Same pricing procedure as non ODs. Free pricing at the manufacturer level but the Norwegian Medicines Agency (NoMA) sets maximum prices at the pharmacy purchasing price (PPP) level for all prescription only medicine via external reference pricing. The pharmacies’ mark-up on the PPP is also regulated.[14]	Reimbursement through the standard process but special consideration may be made for chronic rare diseases.[10]
	Evaluated by the Norwegian Knowledge Centre for the Health Services.[14]
Spain	Undergo the same HTA procedure as non ODs.[11,13]	Same pricing procedure as non ODs.[11]	Reimbursement through the standard process but more likely to be approved.[13]
	Evaluated by national and regional HTA.[11]	The price is decided on the national level based on cost-effectiveness, budget restrictions, reference pricing, value-based pricing, three years’ sales forecasts and manufacturer’s profit.[11]	Decision made by the regional governments
			Reimbursed through hospital channel or specialist centres.[11]
Sweden	Undergo the same HTA procedure as non ODs however, less robust HTA assessment may be used for ODs.[8,11]	Same pricing procedure as non ODs. Free pricing.[8]	Reimbursement through the standard process.
	Evaluated by the Dental and Pharmaceutical Benefit Agency (TLV).[8,11]		Decisions taken by the Dental and Pharmaceutical Benefits Agency (TLV) and approved by the Public Social Insurance based on cost-effectiveness, human value, need and solidarity.[8,11]
	County Councils (regional HTA agencies) may decide to reimburse ODs independently of TLV recommendation.[8,11]		Several ODs approved for reimbursement despite weak cost-effectiveness data, showing a propensity to accept lower levels of evidence for ODs where limited budget impact is expected.[7]
	No specific HTA criteria applied by the County Councils, decisions are done on case by case basis.[8,11]
UK	Undergo the same HTA procedure as non ODs but NICE and SMC accepts higher uncertainty regarding clinical evidence requirements and apply adjusted criteria for cost-effectiveness threshold.[11,15]	Same pricing procedure as non ODs. Free pricing but must meet profit control criteria applied also to non ODs.[4]	Reimbursement through the standard process.[11]
	SMC has introduced the Patient and Clinician Engagement (PACE) in additional to the standard HTA framework to support HTA decisions for ODs.[11,16]		NICE bases decision on cost-effectiveness although additional criteria, such as equity may also be considered.[11]
	PACE enables the consideration of added benefits of the drug, from both patient and clinician perspectives that may not be fully captured within the conventional HTA.[16]		SMC bases decision on clinical efficacy and cost-effectiveness.[11]

Table 2. Number of comparable orphan drugs analysed per country.

	Number of orphan drugs with available price	Number of orphan drugs compared to the UK (UK = 94)
France	67	65
Germany	68	62
Italy	83	76
Norway	67	61
Spain	42	40
Sweden	35	35

Figure 1. Mean, median, minimum, maximum ratios per country using UK as reference.

Figure 2. Percentage of orphan drugs (OD) under four cost ratio categories.

Figure 3. Averaged ratios when the UK reference list was divided into four quartiles based on UK costs. Quartile 1 includes orphan drugs with the highest annual treatment costs in the UK and quartile 4 includes orphan drugs with the cheapest annual treatment costs in the UK.

Figure 4. Averaged ratios when the UK reference list was divided into eight disease areas.

Figure 5. Averaged ratios for top three disease areas with most orphan drugs available in the UK.

Table 3. Available literature on orphan drug prices in the EU.

Publication	Year	Geographical scope	N of OD analysed	Methodology	Results
Alcimed [31]	2004	EU-25	10	For each OD, the manufacturer’s price before taxes (MPBT, ex-factory) was compared to the lowest in all countries and the ratios were averaged by country.	The maximum variations between countries are not very different, on average 122% of the lowest price (105–173%).
					Germany and France had the highest prices.
					Spain, Portugal, and the UK had the lowest prices.
				For each OD, the public price including taxes (PPIT) were used to compute for annual cost per patient and country comparison done.	The PPIT cost variations were greater than MBPT (above), and may reach 70%.
					Austria has the highest annual cost per patient.
					Followed by Germany and Denmark.
					Then, Finland, France, Ireland.
					Then, Spain, Portugal, UK and Sweden.
Eurordis [5]	2010	10: Belgium, Denmark, France, Greece, Hungary, Italy, The Netherlands, Romania, Spain, Sweden	60	For each OD, the ‘national price’* was compared to the lowest in the 10 countries and the ratios were averaged by country.	Italy: 150–160%
					Denmark and Greece: 140–150%
					Hungary and Spain: 110–120%
					Belgium, France, and Romania:100–110%
				For each OD, the ‘national price’ was compared to the mean value in the 10 countries and the ratios were averaged by country.	Italy: 120–130%
					Denmark and Greece: 110–120%
					Hungary and Spain: 90–100%
					Belgium, France, and Romania: 80–90%
Macarthur, D [32]	2011	7: France, Germany, Italy, Spain, Sweden, Switzerland, UK	60	Direct comparison of public prices.	When Italian price was available (N = 45), it was highest in the EU-5 except for three drugs.
					When UK price was available (N = 56), it was the cheapest in the EU-5 except for eight cases.
			12	Direct comparison of ex-factory price (estimated by deducting distribution margins and VAT from public price).	Germany tended to have the highest ex-factory prices in the EU-5.
					UK had most of the lowest ex-factory prices. Some more recent drugs had higher prices.
					Swiss prices were higher than in Germany.

*‘National price’ was not defined

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