Aducanumab As a Treatment for Alzheimer’s Disease (AD)

Aducanumab

Aducanumab (aka BIIB037) is a high-affinity, recombinant, fully human anti-Aβ IgG1 monoclonal antibody (mAb) that recognizes a neoepitope of disease-associated proteins (e.g., a disease specific variant of an endogenous protein) which derive from a native endogenous protein but are prevalent in the body of a patient in a variant form and/or out of their normal physiological context. 

Technology for a method of providing disease-specific binding molecules and targets was assigned to the University of Zürich in Switzerland as covered in the following US issued patent (US 9,670,272 B2). 

Biogen manufactured BIIB037 based on the method licensed from the University of Zürich.

Patent(s)

  • US Patent Number: US 9,670,272 B2 (issued on June 6, 2017).
    • A method of obtaining a monoclonal antibody specific for a pathological variant of an endogenous protein associated with a disorder characterized by the presence of pathological protein structures of the pathological variant of the endogenous protein, wherein the variant of the endogenous protein is derived from beta-amyloid or AIAPP (islet amyloid polypeptide). 
  • Patent PDF download at https://patentimages.storage.googleapis.com/00/0a/e8/6fa374058e229a/US9670272.pdf 

Clinical Trials

  • Phase 1 (PRIME)
    • ClinicalTrials.gov ID: NCT01677572
    • Experimental drug: 221AD103
    • 197 participants
  • Phase 2 (EVOLVE)
    • ClinicalTrials.gov ID: NCT03639987
    • Experimental drug: 221AD205
    • 57 participants
  • Phase 3 (ENGAGE)
    • ClinicalTrials.gov ID: NCT02477800
    • Experimental drug: 221AD301
    • 1647 participants
  • Phase 3 (EMERGE)
    • ClinicalTrials.gov ID: NCT02484547
    • Experimental drug: 221AD302
    • 1638 participants
  • Phase 3b
    • ClinicalTrials.gov ID: NCT04241068
    • Experimental drug: Aducanumab at 10 mg/kg by intravenous
      (IV) infusions every four (4) weeks for a total duration of 100 weeks.  
    • This is 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 (i.e. previously treated participants) or who had previously received placebo (i.e. treatment-naïve participants).
    • 2400 participants in estimated enrollment based on the Aducanumab studies (aka “feeder studies”) involving 221AD103, 221AD301, 221AD302 and 221AD205.
    • Estimated Primary Completion Date: September 1, 2023
    • Estimated Study Completion Date: September 1, 2023

“Alzheimer’s disease remains one of the greatest public health challenges of our time. It robs memories, independence and eventually the ability to perform basic tasks from the people we love,” said Michel Vounatsos, Chief Executive Officer at Biogen. “The aducanumab BLA is the first filing for FDA approval of a treatment that addresses the clinical decline associated with this devastating condition, as well as the pathology of the disease. We are committed to driving progress for the Alzheimer’s disease community and look forward to the FDA’s review of our filing.”

“People living with Alzheimer’s, their families, caregivers and so many others in the community are fighting this disease every day, and the global social burden of the disease is expected to grow as the population ages,” said Dr. Haruo Naito, Chief Executive Officer at Eisai Co., Ltd. “The BLA submission is an important step in the fight against this disease, for which pathophysiological progression currently cannot be stopped, delayed or prevented.”

As listed above for clinical studies for aducanumab,, there were two Phase 3 trials (EMERGE and ENGAGE) in patients with early stage Alzheimer’s disease (enrolled patients had mild cognitive impairment (MCI) due to Alzheimer’s disease and mild Alzheimer’s disease dementia with Mini-Mental State Examination (MMSE) scores of 24-30).

In EMERGE, patients who received aducanumab experienced significant slowing of decline on measures of cognition and function such as memory, orientation and language. Patients also experienced slowing of decline on activities of daily living including conducting personal finances, performing household chores, such as cleaning, shopping and doing laundry, and independently traveling out of the home.

EMERGE (n=1,638)

EMERGE trial met its pre-specified primary endpoint, with patients treated with high dose aducanumab showing a statistically significant reduction of clinical decline from baseline in Clinical Dementia Rating-Sum of Boxes (CDR-SB) scores at 78 weeks (22% versus placebo, P=0.01). Patients treated with high dose aducanumab also showed a consistent reduction of clinical decline as measured by the pre-specified secondary endpoints: the Mini-Mental State Examination (MMSE; 18% versus placebo, P=0.05), the Alzheimer’s Disease Assessment Scale-Cognitive Subscale 13 Items (ADAS-Cog 13; 27% versus placebo, P=0.01) and the Alzheimer’s Disease Cooperative Study-Activities of Daily Living Inventory Mild Cognitive Impairment Version (ADCS-ADL-MCI; 40% versus placebo, P=0.001). Imaging of amyloid plaque deposition in EMERGE demonstrated that amyloid plaque burden was reduced with low and high dose aducanumab compared to placebo at 26 and 78 weeks (P<0.001).

ENGAGE (n=1,647)

While ENGAGE did not meet its primary endpoint, Biogen believes a subset of data from ENGAGE are supportive of the outcome in EMERGE.

Biogen recently completed its submission of Biologics License Application (BLA) for Aducanumab to the US Food and Drug Administration (FDA)

Last Updated: 2020-07-10

 

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