Demonstrating significant benefit of orphan medicines: analysis of 15 years of experience in Europe

Fregonese, Laura; Greene, Lesley; Hofer, Matthias P.; Magrelli, Armando; Naumann‐Winter, Frauke; Larsson, Kristina; Sheean, Maria E; Stoyanova-Beninska, Violeta; Tsigkos, Stelios; Westermark, Kerstin; Sepodes, Bruno

doi:10.1016/j.drudis.2017.09.010

Cited by 20 publications

(9 citation statements)

References 11 publications

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“…One important reason for the different application of ‘orphan status’ in the USA and the EU could be the different legal prerequisites for orphan designation. The demonstration of ‘significant benefit’ is mandatory for drugs to be designated with orphan status by the EMA compared with those drugs already on the market targeting the same disease 15 34 36. ‘Significant benefit’ means that a drug has a clinically relevant advantage or makes a major contribution to patients’ care, compared with existing drugs already on the market that target the same condition 33 37.…”

Section: Discussionmentioning

confidence: 99%

“…Significant benefit is a higher standard than the positive benefit-risk assessment that must be demonstrated by the sponsor in the marketing approval process, which does not involve an obligation to show that such a drug is more beneficial than all other methods for treating the same condition 19. Significant benefit is required at the time of orphan designation, when it can be supported by preclinical studies, and at the time of marketing approval, when clinical data are needed 36. Our study has shown that a few drugs had their orphan drug designations withdrawn during the marketing approval process, including olaparib (Lynparza) for treatment of primary peritoneal cancer, ovarian cancer, and fallopian tube cancer, and bosutinib (Bosulif) for treatment of chronic myelogenous leukaemia in the EU.…”

Section: Discussionmentioning

confidence: 99%

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Application of orphan drug designation to cancer treatments (2008–2017): a comprehensive and comparative analysis of the USA and EU

Vokinger

Kesselheim

2019

BMJ Open

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ObjectiveTo determine differences in the characteristics of cancer drugs designated as orphan drugs by the Food and Drug Administration (FDA) and European Medicines Agency (EMA).Design and settingIdentification of all cancer drugs (initial or supplementary indication) with orphan status approved by the FDA between 2008–2017 based on publicly accessible reports. The European public assessment reports (EPAR) was searched to determine whether these FDA-approved drugs were also approved by the EMA.Main outcome measuresExtraction of active ingredient, trade name, approval date and approved indication from two FDA data sources (Orphan Drug Product Designation Database, Drugs@FDA) and comparison with the same data from EPAR.ResultsThe FDA approved 135 cancer drugs with orphan indications that met our inclusion criteria, of which 101 (75%) were also approved by the EMA. 80/101 (79%) were first approved in the USA. Only 41/101 (41%) also received orphan designation by the EMA. 33/101 (33%) were approved for biomarker-based indications in the USA, however, only nine approved cancer drug indications by the EMA were biomarker-derived drugs. 78% (47/60) of approved cancer drugs that were only approved in the USA with orphan status were indicated for solid tumours, 22% (13/60) had indications for non-solid tumours. By contrast, out of those approved cancer drugs that received orphan designation by both agencies, 20% (8/41) were indicated for solid, and 80% (33/41) for non-solid tumours.ConclusionsOrphan designation was intended to encourage drug development for rare conditions. This study shows that the FDA approves more cancer drugs with such designations compared with the EMA, especially for subgroups of more prevalent cancers. One reason for the difference could be that the European Union requires demonstration of significant benefit for drugs that target the same indication as a drug already on the market to earn the orphan designation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Application of orphan drug designation to cancer treatments (2008–2017): a comprehensive and comparative analysis of the USA and EU

Vokinger

Kesselheim

2019

BMJ Open

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“…The requirement to show that a product for which an OD is applied will be of significant benefit to those affected by the orphan condition in cases where other satisfactory methods exist is a unique criterion in the EU Orphan Regulation framework. The concept of significant benefit has been discussed previously in a number of publications (2,3). The need to demonstrate significant benefit is of particular importance as it may be effectively gatekeeping in nature (e.g., blocking new products from obtaining a designation or preventing incentives such as the 10 years of market exclusivity due to lack of adequate comparative data).…”

Section: Defining a Satisfactory Methods Of Treatmentmentioning

confidence: 99%

Defining Satisfactory Methods of Treatment in Rare Diseases When Evaluating Significant Benefit–The EU Regulator's Perspective

et al. 2021

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Since the implementation of the EU Orphan Regulation in 2000, the Committee for Orphan Medicinal Products at the European Medicines Agency has been evaluating the benefits of proposed orphan medicines vs. satisfactory treatment methods. This type of evaluation is foreseen in the Orphan Regulation as the orphan designation criterion called the “significant benefit.” In this article, based on 20 years of experience, we provide a commentary explaining what is considered a satisfactory method of treatment in the context of the EU Orphan Regulation and for the purpose of the assessment of significant benefit. We discuss the challenges posed by continuously changing clinical practise, which is associated with the increasing number of treatment options, evolving nature of medicinal therapeutic indications and our understanding of them.

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“…This problem is particularly pronounced at the time of confirming ODD when indirect comparisons must be made (in the absence of clinical evidence), for which there is currently no agreed standard methodology ( Fregonese et al, 2018 ; Nicolodi 2019 ). In addition, confirmation of ODD is required when the therapeutic indication is significantly broadened and may also be required 5 years after obtaining the market authorisation.…”

Section: The Policy Proposalsmentioning

confidence: 99%

Orphan Medicine Incentives: How to Address the Unmet Needs of Rare Disease Patients by Optimizing the European Orphan Medicinal Product Landscape Guiding Principles and Policy Proposals by the European Expert Group for Orphan Drug Incentives (OD Expert Group)

Aartsma‐Rus

Dooms²,

Cam³

2021

Front. Pharmacol.

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Today policy makers face the challenge to devise a policy framework that improves orphan medicinal product (OMP) development by creating incentives to deliver treatments where there are none and to authorize innovative and transformative treatments where treatments already exist. The European Expert Group on Orphan Drug Incentives (hereafter, OD Expert Group) came together in 2020 to develop policy proposals to facilitate EU policy makers to meet this challenge. The group brings together representatives of the broad rare disease community, including researchers, academia, patient representatives, members of the investor community, rare disease companies and trade associations. The group’s work builds on the recognition that only an ambitious policy agenda developed in a multi-stakeholder setting can bring about the quantum leap needed to address unmet needs of rare disease patients today. Along the OMP development path, the OD Expert Group has identified four main needs that a policy revision should address: 1) Need to improve the R&D ecosystem for basic research and company take-up of development. 2) Need to improve the system of financial incentives and rewards. 3) Need to improve the flexibility, predictability and speed of the regulatory pathway. 4) Need to improve the coherence and predictability of demand and pricing for OMPs. This article presents the results of the OD Expert Group work as a set of guiding principles that the revision of the policy framework should follow and a set of 14 policy proposals that address the main needs of OMP development in Europe today.

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Demonstrating significant benefit of orphan medicines: analysis of 15 years of experience in Europe

Cited by 20 publications

References 11 publications

Application of orphan drug designation to cancer treatments (2008–2017): a comprehensive and comparative analysis of the USA and EU

Application of orphan drug designation to cancer treatments (2008–2017): a comprehensive and comparative analysis of the USA and EU

Defining Satisfactory Methods of Treatment in Rare Diseases When Evaluating Significant Benefit–The EU Regulator's Perspective

Orphan Medicine Incentives: How to Address the Unmet Needs of Rare Disease Patients by Optimizing the European Orphan Medicinal Product Landscape Guiding Principles and Policy Proposals by the European Expert Group for Orphan Drug Incentives (OD Expert Group)

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