Amendments to the European pharmacovigilance legislative framework are expected to come into force in 2011, following the adoption of the proposed amendments to Directive 2001/83/EC on the community code relating to medicinal products for human use (hereinafter referred to as the Directive) and to Regulation (EC) No. 726/2004 laying down community procedures for the authorization and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency (EMA) [hereinafter referred to as the Regulation]. The Regulation shall apply 18 months after publication in the Official Journal of the European Union. The amendments to the Directive and the Regulation will induce changes in the EU in terms of evaluation of risk associated with medicinal products as well as the framework on how the EU takes harmonized regulatory action on drug safety. In this review, the text agreed between the European Parliament and Council is examined and compared with the pharmacovigilance legislative framework currently in force. We argue that the new legislation has improved numerous uncertainties in current legislative framework and provides for the following: (i) clear roles, responsibilities and obligations for the key responsible parties; (ii) rationalization of EU decision making on drug safety issues in order to deliver measures that are equally and fully implemented for all relevant products across the community with a view to preventing unnecessary patient exposure to risks; (iii) strengthening medicine safety transparency and communication so that the understanding and trust of patients and health professionals in the safety of medicines will improve, as well as the penetration of key warnings; (iv) strengthening companies' pharmacovigilance systems, allowing companies to improve their systems constantly while reducing administrative burden; (v) ensuring the proactive and proportionate collection of high-quality data relevant to the safety of medicines through risk management and structured data collection in the form of Post-Authorization Safety Studies (PASS), together with rationalized single-case and periodic reporting of suspected adverse drug reactions (ADRs); (vi) involvement of stakeholders in pharmacovigilance through direct patient reporting of suspected ADRs and inclusion of patients and healthcare professionals in decision making; and (vii) simplification of the current community pharmacovigilance procedures with consequent efficiency gains for both the pharmaceutical industry and medicines regulators. For the first time, companies can be made legally liable to carry out PASS and Post-Authorization Efficacy Studies. The amendments to the Regulation and to the Directive will strengthen the European network on pharmacovigilance. A Pharmacovigilance Risk Assessment Committee (PRAC) based at the EMA will be set up, which will be responsible for all matters related to pharmacovigilance at an EU level. Three European databases will be strengthened (EudraVigilance, EudraPharm and the Europ...

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.

Despite extensive research, no disease-modifying therapeutic option, able to prevent, cure or halt the progression of Alzheimer’s disease [AD], is currently available. AD, a devastating neurodegenerative pathology leading to dementia and death, is characterized by two pathological hallmarks, the extracellular deposits of amyloid beta (Aβ) and the intraneuronal deposits of neurofibrillary tangles (NFTs) consisting of altered hyperphosphorylated tau protein. Both have been widely studied and pharmacologically targeted for many years, without significant therapeutic results. In 2022, positive data on two monoclonal antibodies targeting Aβ, donanemab and lecanemab, followed by the 2023 FDA accelerated approval of lecanemab and the publication of the final results of the phase III Clarity AD study, have strengthened the hypothesis of a causal role of Aβ in the pathogenesis of AD. However, the magnitude of the clinical effect elicited by the two drugs is limited, suggesting that additional pathological mechanisms may contribute to the disease. Cumulative studies have shown inflammation as one of the main contributors to the pathogenesis of AD, leading to the recognition of a specific role of neuroinflammation synergic with the Aβ and NFTs cascades. The present review provides an overview of the investigational drugs targeting neuroinflammation that are currently in clinical trials. Moreover, their mechanisms of action, their positioning in the pathological cascade of events that occur in the brain throughout AD disease and their potential benefit/limitation in the therapeutic strategy in AD are discussed and highlighted as well. In addition, the latest patent requests for inflammation-targeting therapeutics to be developed in AD will also be discussed.

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