A contentious FDA ruling for Alzheimer's disease

On June 7, 2021, the US Food and Drug Administration (FDA) finally made its decision on aducanumab, anti-amyloid drug that has been subject of a prolonged controversial approval process. Contrary to recommendation their Peripheral Central Nervous System Advisory Committee (PCNSDAC), FDA surprisingly approved aducanumab for treatment Alzheimer's disease. The ruling split neurology community, with some clinicians researchers welcoming as needed boost field others believing does not follow data available. PCNSDAC basis safety efficacy whereas new was unexpectedly under FDA's accelerated pathway, which means can be based surrogate or intermediate clinical endpoint instead demonstrated benefit. For reduction amyloid β plaque. In wake approval, three nine core voting members resigned. defended change mechanism stated that, despite uncertainties about benefit they had listened patient advocacy groups decided benefits outweighed risks. It is unusual drugs undergo approval; by end 2020, more than 250 candidates this pathway in USA, mostly cancer but also rare disorders such Duchenne muscular dystrophy. Use process rather an lead faster chronic diseases. With have outlined expectation burden reasonably likely result future Whether European Medicines Agency will consider expedited unknown. indications USA criticised many being line inclusion exclusion criteria phase 3 trials (EMERGE ENGAGE). example, prescribing label restrict use people early-stage disease confirmed status. cost US$56 000 per year, lack guidance who should prescribed huge implications, only neurologists wondering how manage patients health insurance system. A further potential hazard possibility off-label other conditions implicated, cerebral angiopathy. predominant adverse event amyloid-related imaging abnormalities (ARIA), presence angiopathy could increase likelihood ARIA. comes caveats. manufacturer drug, Biogen, must complete 4 confirmatory trial shows efficacy. However, period within completed fixed, requiring sufficient duration, Biogen results available until 2030. 9-year wait confirmation unacceptable paying receiving ineffective treatment. enforce requirement ensure completed, back up bolster regulatory Three investigational monoclonal antibody treatments are very similar target (donanemab, gantenerumab, lecanemab) trials. 24, announced it granted breakthrough therapy designation donanemab lecanemab. This enables through development review serious life-threatening conditions. donanemab, Eli Lilly, subsequently intention apply later 2021. precedent now set targeted therapies, implications research funding huge. intense scrutiny, countries outside looking on, clinicians, researchers, policy makers come together conducted patients' closely monitored requirements met. Off-label angiopathyThe & disease.1 Approval provided treat fill unmet need, plaques brain. Full-Text PDF Rapid access scientific rigour: delicate balanceDespite substantial associated disease, no pharmacotherapies licensed since 2003. Aducanumab, human targets reduces accumulations brain, defining pathology considered Drugs Nov 6, 2020. Although final may March surrounding evaluation caused controversy. resurrection diseaseOn Mar 21, 2019, failed futility analyses two identically designed trials, discontinued . Oct 22, surprise announcement were applying marketing aducanumab. company explained reanalysed from include continued studies Dec 26, 2018, cut-off date when announced.