Nonclinical data supporting orphan medicinal product designations: lessons from rare neurological conditions

Sheean, Maria E; Stoyanova-Beninska, Violeta; Capovilla, Giuseppe; Duarte, Dinah; Hofer, Matthias P.; Hoffmann, Michel; Magrelli, Armando; Mariz, Segundo; Tsigkos, Stelios; Shaili, Evyenia; Polsinelli, Benedetta; Ricciardi, Mario; Bonelli, Milton; Balabanov, Pavel; Larsson, Kristina; Sepodes, Bruno

doi:10.1016/j.drudis.2017.09.015

Cited by 16 publications

(6 citation statements)

References 156 publications

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“…For example, unavailability of pharmacological treatments for rare diseases or delays between the expiration of intellectual property protections and the marketing of complex copies suggest that regulatory frameworks still have to find an optimal balance between regulatory assessment of the benefit-risk balance and economic sustainability. In the case of rare diseases, nonclinical models have been implemented for predicting the therapeutic value of new or repositioned drug products [80]. In the case of complex copies, the use of in vitro comparability studies in place of clinical studies could be a good strategy for reducing pre-marketing economic investments.…”

Section: Discussionmentioning

confidence: 99%

Old active ingredients in new medicinal products: is the regulatory path coherent with patients’ expectations?

Minghetti

Musazzi²,

Casiraghi³

et al. 2020

Drug Discovery Today

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Section: Discussionmentioning

confidence: 99%

Old active ingredients in new medicinal products: is the regulatory path coherent with patients’ expectations?

Minghetti

Musazzi²,

Casiraghi³

et al. 2020

Drug Discovery Today

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“…The evaluation needs to be performed both at the initial stage of OD and when reviewing maintenance of orphan status at the time of marketing authorisation (MA). The assessment at the time of OD is made early in the medicine development, often at the stage of non-clinical studies (4,5), whereas the assessment at maintenance stage takes place after the medicine receives a positive opinion from the Committee of Human Medicinal Products (CHMP) at EMA following a positive benefit/risk assessment.…”

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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“…The validity of the non-clinical in vivo model used is of paramount importance in COMP discussions. Issues relating to "face validity" (the recapitulation of disease manifestations), "construct validity" (replication of the pathophysiology of the condition), and "predictive validity" (ability to allow for conclusions relevant for the human disease) may be considered in relevant deliberations (8)(9)(10). In case valid models of the proposed condition are not available, or the conduct of nonclinical studies in existing models was not possible due to e.g., cross-species limitations, bridging to other models or to data obtained with surrogate products may be exceptionally considered (11).…”

Section: Medical Plausibilitymentioning

confidence: 99%

Regulatory Standards in Orphan Medicinal Product Designation in the EU

et al. 2021

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Twenty years of orphan regulation in Europe have now elapsed, with almost 2,400 orphan designated medicinal products and more than 190 orphan products authorised in the EU. Alongside the evolution in understanding of rare diseases, considerable regulatory knowledge has also been accumulated regarding the level of evidence that would support inclusion of products into the framework. This article reviews publications and regulatory documents pertaining to orphan medicinal product designation in the EU and discusses the general expectations in submitted applications as reflected in the current regulatory practise. Important elements to recommend granting a European orphan designation are the key considerations of orphan condition, medical plausibility, seriousness, and prevalence, while significant benefit is also assessed when there are authorised medicinal products for the sought indication. This review attempts to clarify the specific concepts currently used in that regard and discusses how the available data can be used to justify the criteria for designation. Moving away from theoretical expectations or assumptions, it stresses that the applications have to be complemented with nosological and epidemiological justifications pertaining to the proposed condition, as well as relevant data in specific non-clinical in vivo models or in affected patients to support inclusion into the orphan scheme.

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Nonclinical data supporting orphan medicinal product designations: lessons from rare neurological conditions

Cited by 16 publications

References 156 publications

Old active ingredients in new medicinal products: is the regulatory path coherent with patients’ expectations?

Old active ingredients in new medicinal products: is the regulatory path coherent with patients’ expectations?

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

Regulatory Standards in Orphan Medicinal Product Designation in the EU

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