As of August 2021, aducanumab (ADUHELM™) has been launched in the US for the treatment of Alzheimer’s disease  .
In June 2021, the US FDA granted accelerated approval for aducanumab (ADUHELM™), for the treatment of Alzheimer’s disease. The approval was based on data from the phase III EMERGE, ENGAGE and PRIME clinical trials [see trials below], demonstrating the effect of the drug on reducing amyloid beta plaques. Under the accelerated approval provisions, Biogen needs to conduct a new randomised, controlled clinical trial to verify the drug’s clinical benefit. If the trial fails to verify clinical benefit, the FDA may initiate proceedings to withdraw approval of the drug. Earlier, in January 2021, the US FDA extended the review period by three months for the Biologics License Application (BLA) for aducanumab and granted new Prescription Drug User Fee Act (PDUFA) action date of June 7, 2021. The US FDA, in August 2020, accepted for priority review, and granted a Prescription Drug User Fee Act (PDUFA) action date of March 7, 2021, for. The FDA also stated that there may be a possibility of early action on the application, under an expedited review. In November 2020, data were presented and opinions were expressed for the review process at the FDA Advisory Committee meeting. Earlier, in July 2020, following a pre-BLA meeting, Biogen completed the rolling BLA submission, which was initiated in April 2020. The submission package included data from the phase III EMERGE and ENGAGE studies, and the phase Ib PRIME study          .
In the first quarter of 2021 Biogen submitted a marketing authorisation application (MAA) to Agência Nacional de Vigilância Sanitária (ANVISA), Brazil for aducanumab for Alzheimer’s disease treatment. The application is in queue for review   .
In the first quarter of 2021, Biogen submitted marketing authorisation applications for aducanumab to Health Canada, the Therapeutic Goods Agency in Australia, and Swissmedic in Switzerland, all of which are subject to agency validation of whether the applications are accepted   .
In December 2020, Biogen has submitted Japanese New Drug Application (J-NDA) to the Ministry of Health, Labor and Welfare (MHLW) for aducanumab in the treatment of Alzheimer’s disease  .
In October 2020, Biogen announced that European Medicines Agency (EMA) accepted Marketing Authorization Application (MAA) of Aducanumab for the treatment of Alzheimer's Disease for review, following a standard timetable. The MAA was submitted in the same month   . In November 2021, Biogen and Eisai announced that following an oral explanation held at the November meeting of the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA), Biogen received a negative trend vote on the aducanumab Marketing Authorization Application for aducanumab 100 mg/mL concentrate solution for infusion for the treatment of Alzheimer’s disease. The CHMP may adopt a formal opinion on the Marketing Authorization Application at its December meeting (December 13-16, 2021). Biogen intends to continue to engage with the EMA and CHMP as it considers next steps towards the goal of providing access to aducanumab to patients in Europe  .
In April 2017, the Japanese MHLW granted SAKIGAKE designation system to aducanumab for the treatment of Alzheimer’s disease in Japan  .
In August 2016, Biogen reported that aducanumab was granted fast track designation by the US FDA, for treatment of early Alzheimer's disease  .
In June 2016, the EMA granted the PRIME (priority medicines) designation to aducanumab for the treatment of Alzheimer’s disease. The PRIME status was granted based on the results of the phase Ib PRIME trial [see below]  .
In October 2019, Biogen reported that after consulting with the US FDA, the company intends to pursue regulatory approval for aducanumab, based on a new analysis conducted by Biogen, of a larger dataset from the phase III clinical studies that were discontinued in March 2019 following a futility analysis. Significant benefits on measures of cognition and function such as memory, orientation, and language were reported in patients who received aducanumab. The analysis includes additional data available after the pre-specified futility analysis demonstrating that aducanumab is pharmacologically and clinically active. The BLA submission will also include data from the phase I/Ib [see below] and phase III [see below] studies. Biogen also intends to offer access to aducanumab to eligible patients previously enrolled in the phase III studies, the long-term extension study for the phase Ib PRIME [see below] study, and the EVOLVE [see below] safety study  .
In October 2019, the Alzheimer's Association reported that Biogen will pursue regulatory approval from the US FDA for aducanumab based on phase III trial results from the EMERGE and ENGAGE studies. The company plans to offer access to aducanumab to eligible patients previously enrolled in the phase III studies, the long-term extension of the phase Ib study, and a safety study  .
As of April 2019, aducanumab was no longer reflecting on Biogen's pipeline and Neurimmune Therapeutics' pipeline, and based on the results of phase III ENGAGE and EMERGE trials, it seemed that the drug development was discontinued (Neurimmune Therapeutics pipeline and Biogen pipeline, April 2019).
In July 2021, Biogen and Eisai released pooled results of the PRIME, EMERGE and ENGAGE trials  . In June 2021, pooled efficacy data for aducanumab in Alzheimer's disease from three clinical trials was released by Biogen  . In the same month, pooled safety and pharmacodynamics results from the phase III EMERGE and ENGAGE trials were presented at the Alzheimer's Association International Conference 2021 (AAIC-2021)   . Later, n November 2021, updated pre-specified pooled analysis from the two pivotal phase III trials namely; EMERGE and ENGAGE trials [see below] were released by Biogen 
In March 2020, Biogen initiated phase IIIb EMBARK trial to evaluate the long-term safety and tolerability of aducanumab after a wash-out period imposed by discontinuation of feeder studies in participants who had previously received aducanumab (previously treated patients) or who had previously received placebo (treatment-naïve patients) (participated in the aducanumab studies PRIME, EVOLVE, EMERGE and ENGAGE; or 221AD103, 221AD301, 221AD302 and 221AD205) (221AD304; EudraCT2019-004368-22; NCT04241068). The first patient was dosed in the same month. The open-label, single group assignment trial intends to enrol 2400 participants in the US, Australia, Austria, Belgium, Denmark, Canada, Finland, France, Germany, Italy, Japan, South Korea, Netherlands, Poland, Portugal, Spain, Sweden, Switzerland, Taiwan, United Kingdom. In November 2020, study design of the ongoing trial was presented at the 2020 Clinical Trials on Alzheimer's Disease digital conference   .
In October 2019, Biogen reported that the phase III EMERGE trial that assessed the efficacy and safety of two dosages of aducanumab in patients with early Alzheimer's disease met its primary endpoint showing a significant reduction in clinical decline in Clinical Dementia Rating-Sum of Boxes (CDR-SB) scores (221AD302; NCT02484547; EudraCT2015-000967-15)  . The double-blind, randomized trial was initiated in July 2015 and completed enrolment of 1 683 patients in the second quarter of 2018, in the US, Belgium, Canada, Finland, France, Germany, Italy, Japan, Netherlands, Poland, Spain, Sweden, Switzerland  . Earlier, in March 2019, Biogen and Eisai terminated the trial based on analysis by an independent data monitoring committee which indicated that the trial was unlikely to meet the primary endpoint upon completion. There were no safety concerns regarding the study drug. In March 2021, efficacy data from the trial was Biogen      . In July 2021, Biogen and Eisai released updated results of the trial. The results were presented at the Alzheimer's Association International Conference (AAIC-2021)   .
In October 2019, Biogen reported that the phase III ENGAGE trial that assessed the efficacy and safety of two dosages of aducanumab in patients with early Alzheimer's disease did not meet the primary endpoint (221AD301; NCT02477800; EudraCT2015-000966-72). The trial was discontinued in March 2019, based on analysis by an independent data monitoring committee which indicated that the trial was unlikely to meet the primary endpoint upon completion. There were no safety concerns regarding the study drug. The double-blind, randomised trial was initiated in June 2015 and completed enrolment of 1 605 patients in the second quarter of 2018, in the US, Australia, Austria, Canada, Denmark, France, Germany, Italy, Japan, Portugal, South Korea, Spain, Taiwan, and the United Kingdom  . The first patient was enrolled in September 2015, thereby triggering a $US60 million milestone payment to Neurimmune       .
In March 2019, Biogen and Eisai announced that the initiation of the aducanumab phase III secondary prevention trial will be assessed while the data from ENGAGE and EMERGE are further evaluated  .
In March 2019, Biogen and Eisai terminated the phase II EVOLVE trial intended to evaluate the safety of aducanumab dosing in asymptomatic amyloid-related imaging abnormalities (ARIA) in patients with mild cognitive impairment due to Alzheimer's disease or with mild AD dementia, based on futility analysis and not based on safety concerns (EudraCT2018-002102-31; 221AD205; NCT03639987). The decision was taken following discontinuation of phase III trials EMERGE and ENGAGE [see above]. The randomised, double-blind, placebo-controlled trial was initiated in December 2018 and intended to enrol approximately 500 patients in the US, the UK, France, Italy and Spain   .
In October 2021, Biogen in collaboration with Eisai Co Ltd, completed a phase I trial of aducanumab (NCT04924140; 221HV103). The primary objective of the study is to evaluate the absolute bioavailability of a single, fixed subcutaneous (SC) dose of aducanumab, compared with a single weight-based intravenous (IV) dose of aducanumab, in healthy volunteers. The secondary objectives of the study are to assess the safety and tolerability of aducanumab, administered SC in healthy volunteers, and to characterise additional pharmacokinetic (PK) parameters of a single, fixed SC dose of aducanumab and a weight-based IV dose of aducanumab in healthy volunteers. The randomised, open-label, parallel-arm study was initiated in June 2021 and enrolled 30 volunteers, aged 40 to 70 years, in the US  .
In December 2016, Biogen completed a randomised, double-blind, placebo-controlled phase I trial that assessed the safety, tolerability, pharmacokinetics and immunogenicity of single and multiple ascending doses of aducanumab in patients with mild to moderate Alzheimer's disease (NCT02434718; 221AD104). The trial was initiated in May 2015 and enrolled 21 patients aged 55 to 85 years, in Japan  .
In November 2016, Biogen completed a phase I trial which evaluated the absolute bioavailability, safety and tolerability of a single, fixed subcutaneous (SC) dose of aducanumab compared with a single, weight-based intravenous (IV) dose in healthy volunteers and to characterise the pharmacokinetics of aducanumab (221HV102; NCT02782975). The randomised, open-label trial initiated in May 2016, enrolled 28 volunteers in the US  .
In August 2013, Biogen Idec completed a phase I trial, which investigated the safety, tolerability and pharmacokinetics of single ascending doses of aducanumab in patients with mild to moderate Alzheimer's disease (NCT01397539). The randomised, double-blind trial was initiated in June 2011 and enrolled 53 patients in the US  . Interim results were presented at the 2013 Alzheimer's Association International Conference in July 2013   . Biogen Idec submitted the IND for the trial in April 2011  .
In In March 2019, the long-term extension phase of the randomised, double-blind, placebo-controlled phase Ib PRIME trial was discontinued which was planned to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple doses of aducanumab in patients with Alzheimer's disease, based on futility analysis and not safety concerns (NCT01677572; EudraCT2012-000349-10). The trial was initiated in October 2012. The primary endpoint is tolerability, assessed from baseline to 30 weeks. Enrolment of 197 patients aged 50 to 90 years was completed in the US in August 2015  . Patients completing the one-year placebo-controlled portion of the study had a long-term extension further. Positive interim results were reported in December 2014 and March 2015. Updated results from the trial were reported in March 2018    . Positive results from a phase Ib study of aducanumab (BIIB037) analysis were presented at the Alzheimer’s Association International Conference in July 2015 (AAIC-2015)  . In December 2016, interim results from the titration cohort as well as data from the first year of the long-term extension (LTE) study were released by the company  . Updated results from the LTE study for patients treated with aducanumab up to 24 months in the titration cohort and up to 36 months in the fixed-dose cohorts were reported in August 2017  . In November 2017, Biogen released new efficacy data from the phase Ib long-term extension trial. Safety data from the LTE was reported in March 2018. Additional safety data was released in August 2018    . The decision was taken following discontinuation of phase III trials EMERGE and ENGAGE [see above]  . In May 2019, data from the long term extension trial were released at the American Academy of Neurology (AAN- 2019)  .
In August 2016, Biogen released results from structural analysis designed to understand the epitope targeted by aducanumab and its binding profile relative to other therapies that showed less efficacy. The study demonstrated that aducanumab was highly selective for aggregated forms of beta-amyloid, including soluble oligomer and insoluble fibril and that non-binding to monomer was critical  .