Aducanumab Therapy to Treat Alzheimer’s Disease: A Narrative Review
Table 1
Studies that evaluated the efficacy or safety of aducanumab.
Trial name, reference, and NCT no.
Country
Design
Participants
Intervention
Results
PRIME (multiple dose study of aducanumab (BIIB037) (recombinant, fully human anti-Aβ IgG1 mAb) in participants with prodromal or mild Alzheimer’s disease) [18] NCT01677572
32 sites in the U.S.A.
RCT phase 1b placebo-controlled multiple dose study
197 patients with prodromal or mild AD
Dose-escalation trial (4 aducanumab doses (1, 3, 6, and 10 mg/kg)) 40 patients from both groups discontinued treatment
165 patient analysis of PET scan showed dose- and duration-dependent reduction of amyloid plaque Terminated after futility analysis of ENGAGE and EMERGE trial on March 21, 2019
Absolute bioavailability of a single fixed subcutaneous dose of aducanumab in healthy participants [37] NCT02782975
2 sites in the U.S.A.
RCT phase 1 open label trial to assess absolute bioavailability
28 healthy volunteers
Single, fixed subcutaneous dose of aducanumab
No results are available Started on May 26, 2016, and completed on Jan 13, 2016
Single ascending dose study of BIIB037 in participants with Alzheimer’s disease [20] NCT01397539
3 sites in the U.S.A.
RCT phase I placebo-controlled single ascending dose study
A total of 53 patients with probable AD with MMSE score of 14–26
Aducanumab () and placebo () Aducanumab was given at doses 0.3, 1, 3, 10, 20, 30, and 60 mg/kg
Aducanumab has adequate safety and tolerability profile and linear PK at
Amyloid PET screening for enrichment of early-stage Alzheimer disease clinical trials: experience in a phase 1b clinical trial [40]
33 sites in the U.S.A.
RCT phase 1b, multicenter, placebo-controlled, multiple-dose study of aducanumab
278 patients with an evaluable PET scan
Ability of PET scan as a tool to identify amyloid plaque-positive patients
Interreader and intrareader agreements from visual readings were 98% and 100%, respectively. Amyloid PET imaging is an effective and feasible screening tool for enrollment of amyloid-positive patients with early stages of AD into clinical trials
PROPEL (single and multiple ascending dose study of aducanumab (BIIB037) in Japanese participants with Alzheimer’s disease) [35] NCT02434718
7 sites in Japan
RCT phase I placebo-controlled, single and multiple ascending dose study
21 Japanese patients with mild to moderate AD To evaluate safety, tolerability, and PK
Single and multiple IV infusion of aducanumab Versus placebo
Started on June 24, 2015, and was completed on December 9, 2016 No results were posted
A study to assess absolute bioavailability of aducanumab in healthy volunteers [38] NCT04924140
2 sites in the U.S.A.
Phase I open label interventional trial to assess bioavailability
30 healthy participants
No results are available
Started on June 11, 2021 Expected to be completed on October 14, 2021
EVOLVE study (a study of aducanumab in participants with mild cognitive impairment due to Alzheimer’s disease or with mild Alzheimer’s disease dementia to evaluate the safety of continued dosing in participants with asymptomatic amyloid-related imaging abnormalities) [41] NCT03639987
22 sites in the U.S.A.
RCT phase II double-blind, controlled study of aducanumab
52 patients with mild MCI or mild AD dementia To evaluate safety of continuing aducanumab dosing in asymptomatic ARIA
Aducanumab
Terminated following futility analysis of ENGAGE and EMERGE trials
ENGAGE (221AD301 phase 3 study of aducanumab (BIIB037) in early Alzheimer’s disease) [43] NCT02477800
181 sites from 14 countries (U.S.A., France, Australia, Spain, Austria, Canada, Denmark, U.K., Germany, Italy, Japan, Korea, Portugal, and Taiwan)
RCT phase III double-blind, placebo-controlled, parallel-group study
1647 patients with mild cognitive impairment or mild Alzheimer’s dementia
Comparison of low-dose aducanumab and high-dose aducanumab and placebo
CDR sum boxes were not different Terminated due to anticipated lack of benefit
EMERGE (221AD302 phase 3 study of aducanumab (BIIB037) in early Alzheimer’s disease) [42] NCT02484547
180 sites from 13 countries (Belgium, Italy, Canada, Finland, France, Sweden, Germany, Japan, Poland, Spain, Switzerland, Netherlands, and U.S.A.)
RCT phase III double-blind, placebo-controlled study
1638 patients with early Alzheimer’s disease with confirmed amyloid pathology
Comparison of low- and high-dose aducanumab and placebo
High-dose aducanumab reduced clinical decline as measured by CDR-SB at 18 months and MMSE, ADAS-Cog 13, ADCS-ADL-MCI
EMBARK (a study to evaluate safety and tolerability of aducanumab in participants with Alzheimer’s disease who had previously participated in the aducanumab studies 221AD103, 221AD301, 221AD302, and 221AD205) [50] NCT04241068
229 sites from 20 countries (Australia, Austria, Belgium, Canada, Denmark, Finland, France, Germany, Italy, Japan, Korea, Netherlands, Poland, Portugal, Spain, Sweden, Switzerland, Taiwan, U.K., and U.S.A.)
RCT phase IIIb with a 24-month treatment period
Planned enrollment of 2400 participants
It will evaluate the long-term safety and efficacy of aducanumab in participants with AD, who will be titrated to receive 10 mg/kg aducanumab by intravenous infusion every 4 weeks
AEs leading to treatment discontinuation or study withdrawal; amyloid-related imaging abnormality-edema (ARIA) or amyloid-related imaging abnormality-hemorrhage or superficial siderosis; and the number of participants with antiaducanumab antibodies
ADUHELM ICARE AD-US study (the first real-world observational phase 4 study in Alzheimer’s disease at AAIC 2021) [36] NTC pending
Approximately 200 sites in the U.S.A.
Observational phase IV prospective, multicenter, noninterventional real-world study
Expected to enroll 6000 participants for 4 years, with at least 16% Latinx and Black/African American patients
The study is aimed at evaluating long-term changes in cognition, function, and neuropsychiatric status among patients treated with aducanumab 100 mg/mL solution for injection
The confirmatory phase IV trial is still under process of being designed and it is expected to monitor the participants for up to 5 years
Abbreviation: AD: Alzheimer’s disease; ADAS-Cog 13: Alzheimer’s disease assessment scale–cognitive subscale (13-item); ADCS-ADL-MCI: Alzheimer’s disease cooperative study–activities of daily living inventory; ARIA: amyloid-related imaging abnormalities; CDR-SB: clinical dementia rating–sum of boxes; MCI: mild cognitive impairment; MMSE: mini-mental state examination; PET scan: positron emission tomography scan; RCT: randomized control trial; U.K.: United Kingdom; U.S.A.: United States of America.
