Do payers value rarity? An analysis of the relationship between disease rarity and orphan drug prices in Europe

Figures & data

Table 1. Drugs used in the analysis with corresponding indication and prevalence.

Drug	Indication simplified	Prevalence per 10,000
Adcetris	Hodgkin disease	1.00
Adempas	Pulmonary hypertension	2.00
Afinitor*	Renal cell carcinoma	4.20
Aldurazyme*	Mucopolysaccharidosis I	0.03
Alprolix**	Haemophilia B	0.20
Arzerra	Chronic lymphocytic leukaemia	3.50
Atriance	Precursor T-Cell lymphoblastic leukaemia-lymphoma	1.10
Blincyto	Precursor cell lymphoblastic leukaemia-lymphoma	1.00
Bosulif	Chronic myeloid leukaemia	1.60
Bronchitol	Cystic fibrosis	1.30
Busilvex*	Conditioning treatment prior to haematopoietic-progenitor-cell transplantation	0.70
Carbaglu	N-acetylglutamate synthetase deficiency	0.00
Cayston	Gram negative bacterial lung infection in cystic fibrosis	1.30
Ceplene	Acute myeloid leukaemia	0.70
Cerdelga	Gaucher disease type 1	0.30
Coagadex**	Hereditary factor X deficiency	0.09
Cometriq	Metastatic medullary thyroid carcinoma	0.70
Cresemba	Mucormycosis	0.06
Cyramza*	Stomach neoplasms (Gastric cancer)	3.00
Cystadane	Homocystinuria	0.17
Dacogen	Acute myeloid leukaemia	1.00
Darzalex**	Plasma cell myeloma	1.75
Defitelio**	Severe hepatic veno-occlusive disease	0.40
Deltyba	Tuberculosis	2.00
Diacomit	Severe myoclonic epilepsy in infancy	0.40
Elaprase	Mucopolysaccharidosis II	0.02
Esbriet	Idiopathic pulmonary fibrosis	3.00
Evoltra	Precursor cell lymphoblastic leukaemia-lymphoma	0.40
Exjade	Iron overload	2.70
Fabrazyme*	Fabry disease	0.03
Farydak	Multiple myeloma	3.20
Firazyr	Hereditary angioedemas	2.50
Firdapse	Lambert-Eaton myasthenic syndrome	0.10
Galafold**	Fabry disease	1.00
Gazyvaro	Chronic lymphocytic leukaemia (follicular lymphoma)	2.40
Gliolan	Malignant glioma	3.70
Glivec*	Chronic myeloid leukaemia	0.90
Glybera	Familial lipoprotein lipase deficiency	0.02
Granupas	Tuberculosis	2.00
Hetlioz**	Non-24-hour sleep-wake disorder	1.85
Holoclar**	Limbal stem cell deficiency	0.30
Iclusig	Chronic myeloid leukaemia	0.80
Idelvion	Haemophilia B	0.10
Ilaris*	Cryopirin associated syndromes	0.05
Imbruvica	Mantle cell lymphoma	0.17
Imnovid	Multiple myeloma	2.20
Increlex	Laron syndrome	2.00
Inovelon	Epilepsy	1.50
Jakavi*	Chronic idiopathic myelofibrosis	0.50
Kalydeco	Cystic fibrosis	1.20
Kanuma	Lysosomal acid lipase deficiency	0.20
Ketoconazole HRA	Endogenous Cushing’s syndrome	0.90
Kolbam	Inborn errors in primary bile acid synthesis	0.07
Kuvan	Phenylketonurias	1.70
Kyprolis	Multiple myeloma	1.30
Lenvima	Differentiated thyroid carcinoma	0.60
Litak*	Hairy cell leukaemia	2.40
Lynparza	Ovarian cancer	2.90
Lysodren*	Adrenal cortex neoplasms	0.10
Mepact	Osteosarcoma	0.50
Mozobil	Hematopoietic stem cell transplantation for multiple myeloma, lymphoma	1.00
Myozyme	Glycogen storage disease type II	0.14
Naglazyme*	Mucopolysaccharidosis VI	0.02
Nexavar	Renal cell carcinoma	3.01
Nexobrid	Deep partial- and full-thickness thermal burns	1.00
Nplate	Thrombocytopenic idiopathic purpura	1.00
Ofev	Idiopathic pulmonary fibrosis	3.00
Opsumit	Pulmonary arterial hypertension	1.80
Orfadin*	Tyrosinemias	0.10
Orphacol	Digestive system diseases, inborn errors of metabolism	0.06
Pedea*	Patent ductus arteriosus	2.13
Peyona	Primary apnoea	0.85
Photobarr*	Barrett oesophagus	3.60
Plenadren	Adrenal insufficiency	4.50
Prialt*	Pain injections, spinal	1.54
Procysbi	Nephropathic cystinosis	0.10
Raxone	Leber’s hereditary optic neuropathy	1.00
Ravicti**	Carbamoyl-phosphate synthase-1 deficiency	0.14
Replagal*	Fabry disease	0.02
Revatio*	Pulmonary hypertension	1.00
Revestive	Short-bowel syndrome	0.20
Revlimid	Multiple myeloma	1.30
Revolade*	Idiopathic thrombocytopenic purpura	2.50
Savene	Extravasation of diagnostic and therapeutic materials	0.03
Scenesse**	Erythropoietic protoporphyria	0.19
Signifor	Cushing’s disease	1.20
Siklos	Sickle cell anaemia	0.50
Sirturo	Pulmonary multidrug resistant tuberculosis	2.00
Soliris	Paroxysmal nocturnal haemoglobinuria	0.10
Somavert	Acromegaly	0.60
Sprycel	Chronic myelogenous leukaemia, BCR-ABL positive	0.89
Strensiq	Hypophosphatasia	0.10
Strimvelis	Adenosine deaminase deficiency	0.02
Sutent*	Malignant gastrointestinal stromal tumours	0.30
Sylvant	Multicentric Castlemans disease who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative	0.99
Tasigna	Chronic myelogenous leukaemia, BCR-ABL positive	1.00
Tepadina	Conditioning treatment prior to allogeneic or autologous haematopoietic progenitor cell transplantation (HPCT) in haematological diseases	0.60
Thalidomide-Celgene	Multiple myeloma	1.20
Thelin	Pulmonary arterial hypertension	0.50
Tobi Podhaler	Pseudomonas aeruginosa lung infection in cystic fibrosis	1.30
Torisel	Renal cell carcinoma	3.50
Tracleer*	Pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension	0.95
Translarna**	Duchenne muscular dystrophy	0.30
Trisenox*	Acute promyelocytic leukaemia	0.80
Unituxin**	Neuroblastoma	1.10
Uptravi	Pulmonary arterial hypertension	1.80
Ventavis*	Primary pulmonary hypertension	2.20
Vidaza	Myelodysplastic syndromes	2.05
Vimizim	Mucopolysaccharidosis, type IVA (Morquio A syndrome)	1.40
Volibris	Pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension	2.00
Votubia	Renal angiomyolipoma with tuberous sclerosis complex	1.00
VPRIV	Gaucher disease	0.30
Vyndaqel	Transthyretin amyloidosis	2.90
Wakix**	Narcolepsy	5.00
Wilzin*	Hepatolenticular degeneration	0.60
Xagrid	Essential thrombocythaemia	2.50
Xaluprine	Acute lymphoblastic leukaemia	1.20
Xyrem*	Narcolepsy	5.00
Yondelis	Sarcoma	0.61
Zavesca	Gaucher disease	0.60

*Orphan designation withdrawn or expired.

** No prices available in the countries in scope; probably not commercially available.

Table 2. Number of orphan drugs analysed per country.

Country	Number of orphan drugs with prevalence of 0–5 per 10,000	Number of orphan drugs with prevalence of 0–1 per 10,000
France	67	36
Germany	68	36
Italy	83	45
Norway	67	36
Spain	42	19
Sweden	35	16
UK	94	52

Figure 1. Orphan drugs annual treatment costs in seven EU countries.

Figure 2. France annual treatment cost per prevalence (0–5 per 10,000).

Figure 3. France annual treatment cost per prevalence (0–1 per 10,000).

Figure 4. Germany annual treatment cost per prevalence (0–5 per 10,000).

Figure 5. Germany annual treatment cost per prevalence (0–1 per 10,000).

Figure 6. Italy annual treatment cost per prevalence (0–5 per 10,000).

Figure 7. Italy annual treatment cost per prevalence (0–1 per 10,000).

Figure 8. Norway annual treatment cost per prevalence (0–5 per 10,000).

Figure 9. Norway annual treatment cost per prevalence (0–1 per 10,000).

Figure 10. Spain annual treatment cost per prevalence (0–5 per 10,000).

Figure 11. Spain annual treatment cost per prevalence (0–1 per 10,000).

Figure 12. Sweden annual treatment cost per prevalence (0–5 per 10,000).

Figure 13. Sweden annual treatment cost per prevalence (0–1 per 10,000).

Figure 14. UK annual treatment cost per prevalence (0–5 per 10,000).

Figure 15. UK annual treatment cost per prevalence (0–1 per 10,000).

Table 3. Available literature assessing the correlation between orphan drugs annual treatment costs and disease prevalence.

Publication	Year	Geographical scope	Number of orphan drugs analysed	Methodology	Results: correlation between annual treatment cost and disease prevalence
Alcimed [36]	2005	France	10	Public price including taxes (PPIT) used	Inverse
Messori et al. [37]	2010	Italy	17	Non-cancer orphan drugs included; Drug prices from Italian national drug regulatory agency used	Inverse
Aballéa et al. [38]	2010	France, Italy, Germany, Spain, UK	51	Public prices used	Inverse
Picavet et al. [14]	2014	Belgium, Czech Republic, France, Italy, the Netherlands, UK	59	Public prices used	Inverse
Onakpoya et al. [39]	2014	UK	74	Annual costs based on literature search	Inverse

Alcimed. Study on orphan drugs. Paris. 2005 [ cited 2016 Jul]. Available from: http://ec.europa.eu/health/files/orphanmp/doc/pricestudy/final_final_report_part_1_web_en.pdf

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Messori A, Cicchetti A, Patregani L. Orphan drugs: relating price determination to disease prevalence. BMJ. 2010;341:c4615.

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Aballea S, Toumi M, Vataire AL, et al. Quantitative analysis of the influence of disease and product characteristics on orphan drug prices in Europe. In: ISPOR 15th Annual International Meeting; 2010 May 15–19; Atlanta, GA. [cited 2016 Jul]. Available from: http://www.creativ-ceutical.com/sites/default/files/ISPOR%20International_Creativ-Ceutical_Orphan%20Drugs%20Poster.pdf

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Picavet E, Morel T, Cassiman D, et al. Shining a light in the black box of orphan drug pricing. Orphanet J Rare Dis. 2014;9:62.

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Onakpoya I, Spencer EA, Thompson MJ, et al. Effectiveness, safety and costs of orphan drugs: an evidence-based review. BMJ Open. 2015;5:e007199.

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