Drugs
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Aducanumab (aducanumab-avwa; Aduhelm™) is a human, immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble and insoluble forms of amyloid β. It has been co-developed by Biogen and Eisai under license from Neurimmune for the treatment of Alzheimer's disease. In June 2021, aducanumab received its first approval in the USA for the treatment of Alzheimer's disease. ⋯ Aducanumab is under regulatory review in Japan and in Europe. Its long-term safety and tolerability is being evaluated in a multinational phase 3b clinical study in patients with early Alzheimer's disease (mild cognitive impairment and mild Alzheimer's disease). This article summarizes the milestones in the development of aducanumab leading to this first approval for Alzheimer's disease.
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Givosiran (Givlaari®) is an δ-aminolevulinic acid synthase 1 (ALAS1)-directed small interfering RNA (siRNA) approved for the treatment of acute hepatic porphyria (AHP). In the phase 3 ENVISION trial, givosiran significantly reduced the annualized rate of composite porphyria attacks (i.e. attacks requiring hospitalization, urgent healthcare visit or intravenous hemin administration at home) compared with placebo in patients with recurrent acute intermittent porphyria (the most common type of AHP) attacks. ⋯ Givosiran offers the convenience of once-monthly subcutaneous administration. Available evidence indicates that givosiran is an important newer therapeutic option for patients with AHP and severe recurrent attacks.
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Progressive fibrosing interstitial lung diseases (ILDs) involve similar pathophysiological processes, indicating the potential for common approaches to treatment. Nintedanib (Ofev®), an intracellular tyrosine kinase inhibitor (TKI) with antifibrotic properties, was one of the first drugs approved for use in idiopathic pulmonary fibrosis (IPF) and has more recently been approved for use in other chronic fibrosing ILDs with a progressive phenotype and systemic sclerosis-associated ILD (SSc-ILD). In multinational phase III trials, nintedanib significantly reduced the annual rate of decline in forced vital capacity (FVC) in adults with IPF, other progressive fibrosing ILDs and SSc-ILD. ⋯ Nintedanib had a manageable tolerability profile in patients with fibrotic ILDs in clinical trials and real-world studies. No new safety signals have emerged from global pharmacovigilance data. Nintedanib continues to represent an important therapeutic option in patients with IPF and is the first drug to be approved for use in patients with other chronic fibrosing ILDs with a progressive phenotype or SSc-ILD, with these approvals expanding the range of fibrotic ILDs for which nintedanib can be prescribed.
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Fabry disease (FD) is a rare X-linked lysosomal storage disease based on a deficiency of α-galactosidase A (AGAL) caused by mutations in the α-galactosidase A gene (GLA). The lysosomal accumulation of glycosphingolipids, especially globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3, deacylated form), leads to a multisystemic disease with progressive renal failure, cardiomyopathy with potentially malignant cardiac arrhythmias, and strokes, which considerably limits the life expectancy of affected patients. Diagnostic confirmation in male patients is based on the detection of AGAL deficiency in blood leukocytes, whereas in women, due to the potentially high residual enzymatic activity, molecular genetic detection of a causal mutation is required. ⋯ In chaperone therapy, there are carriers of amenable mutations that show limited clinical success. This article provides a brief overview of the clinical picture in FD patients, diagnostic confirmation, and interdisciplinary clinical management of FD. The focus is on current and future therapeutic options.
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BNT162b2 (Comirnaty®; BioNTech and Pfizer) is a lipid nanoparticle-formulated, nucleoside-modified mRNA vaccine for the prevention of the novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. BNT162b2 encodes the SARS-CoV-2 spike protein, the expression of which elicits immune responses against the antigen in recipients. ⋯ BNT162b2 is administered intramuscularly in a two-dose regimen. This article summarizes the milestones in the development of BNT162b2 leading to these first approvals for the prevention of COVID-19.