Rare pulmonary diseases and orphan drugs: where do we stand and where are we going to?
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ABSTRACT:
SUBMITTER: Harari S
PROVIDER: S-EPMC9487678 | biostudies-literature | 2015 Sep
REPOSITORIES: biostudies-literature
Publications
Rare pulmonary diseases and orphan drugs: where do we stand and where are we going to?
Harari Sergio S Humbert Marc M Blasi Francesco F Collard Harold R HR Matucci-Cerinic Marco M Simonneau Gerald G Vancheri Carlo C Wells Athol U AU Cottin Vincent V
European respiratory review : an official journal of the European Respiratory Society 20150901 137
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Project description:IntroductionRare diseases (RDs) are often chronic and progressive life-threatening medical conditions that affect a low percentage of the population compared with other diseases. These conditions can be treated with medications known as orphan drugs (ODs). Unfortunately, there is no universal definition of RDs or ODs. This systematic review (SR) will identify the quantitative and qualitative criteria and the underlying rationale used internationally to define RDs and ODs.Methods and analysisThis protocol follows the conventions for the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (2015 guidelines). A SR will be conducted, including a search of the following databases: PubMed, MEDLINE, EMBASE, Scopus, Web of Science, GreyLit and OpenGrey. Eligible publications will be selected based on predetermined inclusion criteria. Extracted data will be analysed using thematic and content analyses of qualitative descriptors, whereas quantitative data will be analysed descriptively and reported in the form of frequencies and percentages.Ethics and disseminationNo ethical approval is required since this SR focuses on the secondary analysis of data retrieved from the scientific literature. The outcomes of this SR will be published as part of a PhD thesis, presented at conferences, and published in peer-reviewed journals.Prospero registration numberCRD42021252701.
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Project description:BackgroundThis study examines the dynamics of the eculizumab patenting, orphan designation, and marketing authorization process in different countries and regulatory systems and analyzes drug revenues since its first marketing authorization.MethodsA retrospective case study was conducted. Multiple information sources were used to: determine the status of eculizumab patents; examine the designation of orphan drug status by US, European, Japanese, and Brazilian regulatory authorities to determine registration status and approved clinical indications; estimate the prevalence of associated clinical conditions; investigate the history of the drug manufacturer, Alexion Pharmaceuticals, Inc., and its financialized business model; and examine global eculizumab sales revenues since its first marketing authorization.ResultsOur search yielded 32 patent families divided into 98 applications. The first patent granted was filed in 1995 by Alexion Pharmaceuticals, Inc. in the US. Eculizumab has always been as an orphan drug, except in the Brazilian regulatory agency. All clinical indications approved thus far refer to rare diseases (e.g., paroxysmal nocturnal hemoglobinuria syndrome, atypical hemolytic-uremic syndrome, refractory and generalized myasthenia gravis, and neuromyelitis optica spectrum disorder). Alexion's revenues amounted to more than US$25 billion between 2007 and 2019, showing a growing trend. Eculizumab led sales from the beginning, being the only product in the company's portfolio until 2015. In 2019, the drug accounted for 79.1% of all revenues.DiscussionOur findings show that a strategy focused on obtaining orphan drug designation, expanding therapeutic indications and the geographic range of marketing approvals, extending monopoly periods, and prioritizing public procurement niches has enhanced revenues and helped the company achieve leadership in a highly specific and profitable market.
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Project description:BackgroundOver the past 30 years, the healthcare industry has increasingly turned its attention to rare diseases. Regulators have emphasized the need for clinical research in this area to be patient-centered. However, there is a lack of evidence concerning whether this need is actually met. In this paper, we aim to address this gap.MethodsFirst, we describe the state of patient-centricity in clinical research in rare diseases based on a targeted literature review. Second, we discuss recommendations from scientific bodies on patient-reported outcome (PRO) measures in rare diseases. Third, we analyze data collected from EMA's and FDA's websites concerning rare disease labeling claims and data from Clinicaltrials.gov concerning the use of PRO measures in rare disease pivotal trials. Fourth, we perform an exhaustive literature review on the use of PRO measures in the pharmaceutical industry, including all phases of clinical research, observational/registry studies, and instrument development and validation.ResultsThere is limited information on rare disease patient engagement in study design, recruitment, and retention. None of the initiatives describing methods for developing PRO measures in rare diseases provide the clear guidance clinical researchers need. Only 17.4% of orphan drug labels contain a PRO measure. Less than half of pivotal trials in orphan drugs have a PRO measure as a primary or a secondary endpoint. Although the number of publications about PRO measures in rare diseases has risen in the past fifteen years, our results indicate that substantial improvements are needed to achieve patient-centricity.ConclusionsThe nature and extent of patient engagement in rare disease research is under-documented. The current paradigm for developing and using PRO measures in clinical research is failing to meet the needs of rare disease patients. Not only are PROs rarely used as high-level endpoints in clinical trials or taken into account in labeling claims, they are also under-researched overall - there are too few measures for the multitude of rare diseases. We call for a clear guidance on patient engagement and suggest a realistic approach to the adaptation of PRO strategy to the specific context of clinical research in rare diseases.
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