Aducanumab is an antibody being studied as a potential drug that eases symptoms of Alzheimer’s disease. Antibodies are made by the immune system to fight viruses and bacteria that make us ill, and drug developers say aducanumab is from cloned immune cells (called “monoclonal antibodies”) that help fight dementia by targeting amyloid beta.
Amyloid beta is a protein that occurs naturally in healthy brains but forms clumps or tangles between the brain cells of people with Alzheimer’s disease, causing brain-cell death that leads to symptoms including memory loss. Studies have suggested that aducanumab binds to amyloid beta tangles and reduces them.
Aducanumab’s journey through the FDA approval process has been a mix of promising developments and setbacks. For more on the steps the drug has taken toward becoming available to people with Alzheimer’s disease, possibly in 2021, see below.
While aducanumab doesn’t reverse or cure the deterioration of the brain as dementia kills cells, aducanumab may be able to slow the loss of memory and general cognition (thinking ability) that are hallmark symptoms of Alzheimer’s disease. Orientation and language problems—like losing track of time and place, and not being able to name well-known objects—also improved in test subjects. The drug’s developer, Biogen, even specifically claimed that test subjects saw an increased ability to manage finances, do chores around the house, go shopping, and leave the home independently. These are instrumental acts of daily living (IADLs) that usually become too difficult for people with dementia somewhere around the middle stages of the disease.
Researchers said a majority of the test subjects taking aducanumab showed no negative side effects. In some cases, however, patients experienced swelling in the brain called “amyloid-related imaging abnormalities” (ARIA) and headache.
Critics of aducanumab say that a closer look at the data from trials shows thinking improvements might be overblown or unrelated to the drug itself. There is even debate over whether targeting amyloid beta plaques in the brain actually improves dementia symptoms. The “amyloid hypothesis” says that reducing the plaques will improve cognition, but this has not yet been shown to work in any drugs that went for FDA approval. Aducanumab is trying to be the first.
Aducanumab is also expensive, with the annual costs projected to be around $50,000 for the recommended dosage. Even if the drug is approved by the FDA, which became less likely after an advisory committee meeting in November (see Latest on FDA Approval below), the Centers for Medicaid and Medicare Services can determine for themselves how much Medicaid and Medicare will cover aducanumab if the cost is high and the drug’s effectiveness remains in doubt. PET brain scans to detect amyloid beta plaques would probably be necessary to determine aducanumab coverage, and those are expensive as well.
Drug developer Biogen announced in July 2020 that they had formally applied to the FDA for approval of aducanumab. The company said they submitted more than 2.5 million pages of information, including data from years of clinical trials. Those clinical trials were a roller coaster, including the company fully declaring that testing would end, and then changing its mind. (See History of Drug Trials below.)
The thousands of people participating in aducanumab’s Stage 3 trial will continue to be administered the drug and monitored as the FDA reviews Biogen’s application, but the company has said it believes the drug could earn approval in 2021. The process hit another bump in November 2020, however, when the Peripheral and Central Nervous System Drugs Advisory Committee (these advisory committees are called “AdComms”) reviewed the trial results and voted on whether aducanumab has been shown as effective for treating Alzheimer’s. While the manufacturer Biogen says its results are promising, and FDA reviewers say they agree, the advisory committee voted 0 for yes and 10 for no on whether the drug has been demonstrated effective.
The AdComm’s vote and recommendations are considered by the FDA when a decision is ultimately made, but those voters are outside experts, mostly professors, working as advisers independent of the agency. Scientists within the FDA, in fact, analyzed data from the same trials and reported they were positive, with “favorable results” (click here) in demonstrating effectiveness.
Other drugs have been voted down by AdComms and still ended up being approved by the regulatory agency. Therefore, aducanumab might still become the first new FDA-approved drug for Alzheimer’s symptoms in almost 20 years. The FDA is expected to make its decision by March 2021.
Another possible result is the ordering of a third major trial, which would significantly delay aducanumab being made available to the public. Even if the trial went well, it would mean perhaps three or more years before FDA approval.
Clinical trials are required by the Food and Drug Administration before a pharmaceutical can be approved for use in the public, and aducanumab made it all the way to Phase 3 before an announcement by the drug’s developer, Biogen, that testing had been halted. More than 3,000 patients were part of the trial, but after about 1,700 patients completed 18 months of treatment, Biogen said its researchers determined that statistical modeling (a “futility analysis”) showed the drug wouldn’t work well enough for FDA approval.
When more subjects completed the 18-month treatment, however, and a larger set of data was available, Biogen announced that findings were actually more promising. When assessments of progress in more than 3,000 subjects could be fully analyzed, benchmarks like their scores on the Mini-Mental State Exam (used to measure severity of thinking problems caused by Alzheimer’s) showed improvement compared to those who took a placebo. Also, brain scans showed a reduction in amyloid beta. The FDA approved the resumption of Stage 3 trials early in 2020.
Unfortunately, test subjects are chosen for the study by invitation only, so participation in ongoing trials for aducanumab are not open to the general public.
The FDA process for reviewing applications for approval, called New Drug Applications or NDAs, usually takes around 10 months. Biogen has said the aducanumab application has about 4,500 files with more than 2.5 million pages of data and information. Even if the NDA review takes longer than usual, this still means an answer will probably come in 2021. Biogen believes a decision will be made by March.
Though the FDA would continue to monitor the effects of the drug, to ensure no unexpected side effects from prolonged usage, after approval the drug can be made available widely. People with Alzheimer’s disease, in other words, may have a new medication to take soon.