Leber’s hereditary optic neuropathy (LHON) is a rare, maternally-inherited optic neuropathy caused by mitochondrial DNA point mutations and which can cause blindness. Currently, Raxone (idebenone) is the only available medicinal product authorised to treat LHON within the European Union and LHON remains an unmet medical need. The aim of this article was to summarise interventional clinical trials published over the past 5 years (between 2014 and 2019) with the primary purpose of treating LHON. Therapeutic approaches discussed include modulating agents of the mitochondrial electron transport chain such as Raxone, cysteamine bitartrate and KH176, inhibitors of apoptosis such as elamipretide, gene therapy medicinal products such as GS010 and scAAV2P1ND4 and retinal tissue regeneration medicinal products such as bone marrow-derived stem cells.
Introduction/Study Objectives: The development of biosimilars is challenging due to the complexity of the active substances as well as the strict regulatory requirements to show similarity with a reference medicinal product. This review aims to describe the regulatory experience of approving biosimilars in the European Union (EU) within the EU framework, identify emerging trends in the EU regulatory pathway when approving biosimilars and discuss where the EU biosimilar framework is heading. Methods: Marketing authorisation applications (MAAs) submitted up to 2019 were retrieved from the public domain. The European public assessment report database was searched for approved biosimilars and clinical development programmes of biosimilars belonging to the same class were reviewed. In order to observe if biosimilars released onto the market increased safety concerns, we compared disproportionate adverse event reports pre- and post-licensure. Results: Up to December 2019, 90 MAAs were submitted and 53 biosimilars were approved for 14 different biologicals. Total number of clinical trials (both phase I and III) steadily goes up driven by an increase number of approvals in later years, while the average number of both phase I and III trials decreased over time with some with Pegfilgrastim biosimilars being approved without conducting any phase III clinical trials. No new safety concerns were identified from the analysis of disproportionate adverse event reports. Discussion: Clinical development programmes of biosimilars and the requirements set for biosimilars approval are changing over time. Biosimilars approved seem to be as well tolerated as the reference products when approved based on stringent regulatory requirements. Conclusion: Regulation of biosimilars is progressing as more knowledge is gained.
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