European regulation on orphan medicinal products: 10 years of experience and future perspectives

Westermark, Kerstin; Holm, Birthe Byskov; Söderholm, Mirjam; Llinares-Garcia, Jordi; Rivière, Frida; Aarum, Stiina; Butlen-Ducuing, Florence; Tsigkos, Stelios; Wilk-Kachlicka, Agnieszka; N'Diamoi, Cinzia; Borvendég, J; Lyons, David; Sepodes, Bruno; Bloechl-Daum, Brigitte; Lhoir, André; Todorova, Mariana; Kkolos, Ioannis; Kubáčková, Kateřina; Bosch‐Traberg, Heidrun; Tillmann, Vallo; Saano, Veijo; Héron, Emmanuel; Elbers, Rembert; Siouti, Miranda; Eggenhofer, Judit; Salmon, Patrick; Clementi, Maurizio; Krieviņš, Dainis; Matulevičiene, Aušra; Metz, H; Vincenti, Albert Cilia; Voordouw, Albertha; Dembowska‐Bagińska, Bożenna; Nunes, Ana Corrêa; Saleh, Flavia Mirela; Foltánová, Tatiana; Možina, Martin; Farnell, Josep Torrent i; Beerman, Björn; Mariz, Segundo; Evers, Marie Pauline; Greene, Lesley; Þorsteinsson, Sigurður B.; Gramstad, Lars; Mavris, Maria; Bignami, Fabrizia; Lorence, Annie; Bélorgey, Chantal

doi:10.1038/nrd3445

Cited by 106 publications

(36 citation statements)

References 13 publications

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“…Actually, these regulations have clearly stimulated the development of drugs for rare conditions, even those previously untreatable, as demonstrated in the EU [30]. …”

Section: Discussionmentioning

confidence: 99%

“…So far, great efforts have been made by the European Medicines Agency on the availability of drugs for rare diseases, and continued efforts are still required from the EU, its institutions and Member States [30]. As an example, the Agency is going to shortly launch the Priority Medicines (PRIME) scheme to push on the development of medicines with unmet medical needs.…”

Section: Discussionmentioning

confidence: 99%

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Orphan medicinal products in Europe and United States to cover needs of patients with rare diseases: an increased common effort is to be foreseen

Giannuzzi

Conte

Landi

et al. 2017

Orphanet J Rare Dis

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BackgroundIn the European Union (EU) and United States (US), specific regulations have been released to provide incentives to develop and sell orphan medicinal products.We analysed the status of orphan drugs designated that not yet received a marketing authorisation or already marketed for patients affected by rare diseases in the EU and US up to December 2015. For each drug, the following data were extracted: designation date, active substance(s), orphan condition and indication, trade name, approved therapeutic indication, approved ages, genetic nature of disease and if affects children.ResultsIn the EU, 1264 Orphan Drug Designations have been granted and 133 medicinal products were approved covering a total of 179 indications and 122 rare conditions. Among these, 79 were approved under Regulation (EC)141/2000 (65 still listed in the Orphan Medicinal Products Register and 14 lost the orphan designation but still authorised) and 23 were approved centrally by the European Agency before the Orphan Regulation entered into force. On the other hand, in the US 3082 designations and 415 orphan products, covering a total of 521 indications and 300 rare conditions, were granted. As a result, the mean of designations per year is 79 in the EU and 93.4 in the US, while the mean of approved indications per year is 8.5 in the EU and 15.8 in the US.No orphan product is marketed in the EU for bone and connective tissue, ophthalmic, poisoning/overdose, renal, urinary and reproductive rare diseases. Among the marketed medicinal products, only 46.6% in the EU and 35.2% in the US are approved for children.If all the existing market approvals were merged, 362 additional therapeutic indications in the EU and 72 in the US would be covered.ConclusionsOur data show that notwithstanding the incentives issued, the number of medicines for rare diseases is still limited, and this is more evident in certain therapeutic areas. However, by merging all the existing approvals, patients would benefit of substantial advantages in both geographic areas. Efforts and cooperation between EU and US seem the only way to speed up the development and marketing of drugs for rare diseases.

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“…Actually, these regulations have clearly stimulated the development of drugs for rare conditions, even those previously untreatable, as demonstrated in the EU [30]. …”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Orphan medicinal products in Europe and United States to cover needs of patients with rare diseases: an increased common effort is to be foreseen

Giannuzzi

Conte

Landi

et al. 2017

Orphanet J Rare Dis

View full text Add to dashboard Cite

show abstract

“…The designation as orphan medicinal product is based either on the prevalence of the condition in the community or the insuffi cient return generated by the product to justify the investment [ 9 ]. In addition, the application has also to address the seriousness and debilitating nature of the condition and to address the criteria set out in Article 3(1)(b) of Regulation (EC) No 141/2000 referred to the absence or existence of satisfactory methods [ 7 ].…”

Section: What Are the Criteria For Orphan Designation?mentioning

confidence: 99%

Orphan Drugs for Rare Diseases

Bloechl-Daum¹,

Butlen-Ducuing²,

Llinares-Garcia³

2016

Clinical Pharmacology: Current Topics and Case Studies

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“…Dazu gehören z.B. die wissenschaftliche Beratung bei der Erstellung des Prüfplans, der Erlass der Zulassungsgebühren und die Exklusivität der Vermarktungsrechte [20,21,22,23]. …”

Section: Zulassungsstudien Für Arzneimittel Zur Behandlung Von Seltenunclassified

“…In der Hämatologie und Onkologie werden neue Arzneimittel zunehmend häufig als OD zugelassen - mehr als 50% der in den letzten 10 Jahren von der EMA zugelassenen 64 OD betreffen hämatologische oder onkologische Indikationen [22] - und anschließend, auch aufgrund der eng definierten Anwendungsgebiete, häufig außerhalb der Zulassung (off label) eingesetzt [20,21,22,23,24]. …”

Section: Zulassungsstudien Für Arzneimittel Zur Behandlung Von Seltenunclassified

Neue Arzneimittel in der Onkologie: Merkmale klinischer Zulassungsstudien und Argumente für die rasche Durchführung unabhängiger klinischer Studien nach der Zulassung

Ludwig¹,

Schott

2013

Oncol Res Treat

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Die Zulassung bzw. Indikationserweiterung für alle onkologischen Arzneimittel erfolgt heute in Europa basierend auf der Verordnung (EG) Nr. 726/2004 in einem zentralisierten Verfahren der European Medicines Agency (EMA). Untersuchungen der letzten Jahre haben Mängel in den Zulassungsstudien aufgezeigt. So werden beispielsweise die Vorgaben der EMA nicht immer konsequent beachtet und Studien werden nach Zwischenanalysen, die zu diesem Zeitpunkt eine bessere Wirksamkeit gegenüber dem Vergleichsarm zeigen, vorzeitig abgebrochen. Unsere aktuelle Auswertung der Europäischen Bewertungsberichte (Auswertungszeitraum: 01.01.2009 bis 13.08.2012) zu 29 Wirkstoffen für 39 onkologische Indikationen ergibt, dass sich die Qualität der Zulassungsstudien in verschiedener Hinsicht verbessert hat. So wurden meist die von der EMA und der Food and Drug Administration (FDA) empfohlenen primären Endpunkte - Gesamtüberleben und progressionsfreies Überleben - verwendet und nur eine Studie wurde als Phase-II-Studie ohne Vergleichsarm durchgeführt. Demgegenüber werden die onkologischen Arzneimittel zur Behandlung seltener Leiden (Orphan Drugs) auf der Basis von kleinen Studien zugelassen, die vielfach offen und nicht randomisiert durchgeführt werden und Surrogatendpunkte unter suchen. Nach der Zulassung ist für die Beantwortung der noch offenen patientenrelevanten Fragen die Durchführung von unabhängigen klinischen Studien erforderlich, für die verstärkt öffentliche Gelder bereitgestellt und bürokratische Hürden abgebaut werden müssen. Nur so kann ein effizienter Umgang mit begrenzten Gesundheitsressourcen ermöglicht und die Versorgungsqualität von Tumorpatienten verbessert werden.

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European regulation on orphan medicinal products: 10 years of experience and future perspectives

Cited by 106 publications

References 13 publications

Orphan medicinal products in Europe and United States to cover needs of patients with rare diseases: an increased common effort is to be foreseen

Orphan medicinal products in Europe and United States to cover needs of patients with rare diseases: an increased common effort is to be foreseen

Orphan Drugs for Rare Diseases

Neue Arzneimittel in der Onkologie: Merkmale klinischer Zulassungsstudien und Argumente für die rasche Durchführung unabhängiger klinischer Studien nach der Zulassung

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