Aducanumab is a medicine to treat Alzheimer’s disease by Biogen. The U.S. Food and Drug Administration (FDA) granted the priority review of aducanumab in August 2020. The FDA also set a start date for the Prescription Drug User Fee Act of 7 March 2021.
Currently, the review is in progress. The FDA also said that they would act much sooner if the conditions require it.
The FDA has planning to hold a committee meeting related to the aducanumab application soon. If approved, aducanumab, previously known as BIIB037, would become the first treatment of Alzheimer’s disease.
So, can the drug be a success in treating Alzheimer’s disease? Let’s find out the answers.
What Is Alzheimer’s Disease?
Alzheimer’s is a chronic disorder in which signs of dementia progressively worsen over many years. In the early stages, memory loss is moderate. But with late-stage Alzheimer’s, patients lose communication power and the ability to manage their surroundings. Alzheimer’s is the sixth-leading cause of death in the United States. An individual with Alzheimer’s lives, on average, four to eight years after diagnosis. But they may live for as long as 20 years, depending on other factors.
Excessive protein build-up in and near brain cells causes Alzheimer’s disease. One of the proteins involved is called amyloid, which forms plaques inside brain cells.
To treat this disease, researchers need to find a way to control the build-up of these proteins. Researchers from Biogen exactly did that.
Details About Aducanumab
Aducanumab is an investigational human antibody for the prevention of Alzheimer’s disease. Biogen believes that Aducanumab can improve the patient’s ability to perform daily tasks. These tasks include managing personal finances, doing domestic duties, and travel independently from home.
Neuroimmune scientists collaborated with a research team at the University of Zurich. Together they discovered aducanumab. Biogen licensed aducanumab from Neurimmune under a joint production and licensing deal. Biogen and Eisai have been working together on aducanumab internationally since October 2017. They aim to produce and commercialize the product jointly.
How Does Aducanumab Work?
Alzheimer’s disease’s leading cause is the excessive build-up of protein complexes in the brain. These are also known as amyloid plaques. Amyloid-beta is usually present as a single protein or monomer in the brain. However, it aggregates to clumps in Alzheimer’s disease. Researchers conclude that these clumps contribute to brain cell death.
Aducanumab is an antibody that binds to the beta-amyloid antigen. Through this relationship, aducanumab may decrease the number of amyloid plaques in the brain. As a result, these will slow down neurodegeneration and disease development.
Clinical Trials of Aducanumab for Alzheimer’s
Biogen has funded several clinical trials of aducanumab in humans.
Researchers have performed three Phase 1 trials. They performed tests in healthy volunteers and patients with Alzheimer’s disease in the U.S. and Japan.
Biogen performed a fourth Phase 1 trial in 192 pre-symptomatic and moderate Alzheimer’s patients. The test was randomized, double-blind, placebo-controlled. They named it PRIME and held it at 32 sites in the U.S. The aim was to determine the effects of various aducanumab doses on amyloid plaques. Researchers measured the progress with positron emission tomography imaging. The first 165 patient’s intern results suggested that all aducanumab doses decreased amyloid plaques. After one year, little or no improvement was evident in the placebo community. Higher doses of this drug caused significant reductions. Aducanumab also tended to slow down the rate of cognitive impairment. Researchers presented the findings of the PRIME experiment’s long-term expansion at the 2017 Clinical Trials on Alzheimer’s Disease. A total of 143 patients from the original trial began the long-term expansion analysis. The results of the study showed positive impacts.
Biogen also began two large-scale Phase 3 clinical trials in people with early-stage Alzheimer’s disease. Both tests were randomized, double-blind, and placebo-controlled.
The first trial called ENGAGE: The study aimed to recruit 1,350 patients at 187 locations in North America, Australia, Europe, and Asia.
The second trial called EMERGE: This trial aimed to recruit around 1,650 patients at 194 sites in North America, Australia, Europe, and Asia.
The organization suspended the trials in May 2019. It is because an independent committee found out that the trials would not reach their primary goal. The suspension was based on the initial test results and not on safety issues. However, a later review found that EMERGE had fulfilled its primary objective. Patients taking the most massive dosage of aducanumab found significant benefits. They experienced a substantial decline in cognitive and physical defects development.
What data from clinical trials support potential approval from the FDA?
The “ENGAGE” trial failed to meet its immediate results. But other clinical trial data are suggesting that Aducanumab may be a success. Some promising factors indicate the potential approval of Aducanumab. They are:
- Biogen sent all results from the aducanumab clinical program to the FDA. They include Phase 3 EMERGE and ENGAGE studies and PRIME trials, including long-term extensions.
- EMERGE reached its pre-specified primary endpoint. It showed a meaningful decrease in amyloid protein in patients treated with high-dose aducanumab.
- The findings of the PRIME study indicated that aducanumab decreased the amyloid-beta. But it requires a dose-dependent and time-dependent manner. Analysis of exploratory medical endpoints revealed a substantial decrease in amyloid-beta. The decline lasted for 48 months.
- Imaging of amyloid plaque formation in EMERGE showed a decrease of amyloid plaque. This decline was both at low and high doses of aducanumab relative to placebo at 26 and 78 weeks.
Will The FDA Approve Aducanumab?
Biogen submitted all evidence from the aducanumab clinical program to the FDA. The clinical trial program includes Phase 3 EMERGE and ENGAGE studies and Phase 1b PRIME trials. Biogen has announced that the FDA has approved the priority review submission. They also set the target date of the Prescription Drug Patient Fee Act of 7 March 2021. It is still early to speculate whether or not the FDA will approve aducanumab. But based on the promising data that Biogen got from trials, we can be hopeful. If Biogen succeeds, aducanumab can be a solution to yet untreatable Alzheimer’s disease.
