Aducanumab is an antibody infusion that recently received FDA approval as a drug that eases symptoms of Alzheimer’s disease, especially for people in the early stages. Sold under the brand name Aduhelm, 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 cell death that leads to symptoms including memory loss. Studies have suggested that aducanumab binds to amyloid beta tangles and reduces them.
Aducanumab is not taken as a pill, but rather as an infusion administered in a doctor’s office for one hour every four weeks. The price tag is unfortunately expensive, at around $56,000 per year, but the drugmaker Biogen has said it is working with insurance companies to make out-of-pocket costs much less for those who need it. For more on cost and insurance coverage, see below.
Aducanumab’s journey through the FDA approval process was a mix of promising developments and setbacks until its approval in June 2021. The history of how Aduhelm became available to people with Alzheimer’s disease is described below in “Accelerated Approval by the FDA.”
While aducanumab doesn’t reverse or cure dementia, it may 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. That would mean aducanumab helps with the instrumental acts of daily living (IADLs) that usually become too difficult for people with dementia somewhere around the middle stages of the disease.
Patients taking aducanumab have experienced swelling and bleeding in the brain, a side effect called “amyloid-related imaging abnormalities” (ARIA). Headache, balance problems leading to falls, stomach issues including diarrhea, and disorientation are also possible side effects.
The swelling or bleeding that comes from ARIA can be monitored via brain scans for people taking aducanumab. The drugmaker recommends MRI scans that detect ARIA before the 7th and 12th infusions, as the problems typically develop in the first 12 to 16 weeks of treatment and are asymptomatic (meaning a person can’t feel them happening). During trials, ARIA was detected in 41% of people taking aducanumab, compared to 10% of those in the control group who did not take the drug.
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 had not been shown to work in any drugs that went for FDA approval, until aducanumab became the first. Inflammation and brain cell death are other important factors of Alzheimer’s disease that aren’t related to amyloid-beta.
The bottom line is that some people question whether or not aducanumab works. In 2020, in fact, an advisory board of experts unanimously agreed (10-to-0) that aducanumab should not be approved as effective against Alzheimer’s disease. A year later, it was approved anyway.
Aducanumab is also expensive, costing about $4,312 per infusion or about $56,000 annually. The drugmaker Biogen has said it will not raise the cost of Aduhelm (aducanumab’s brand name) for at least four years, but that price tag might be a problem for people who would be good candidates for infusions. The Centers for Medicaid and Medicare Services (CMS) have yet to determine how much Medicaid and Medicare will cover aducanumab. MRI or PET brain scans to detect amyloid beta plaques would probably be necessary to determine aducanumab coverage, with CMS and private insurers both, and those are expensive as well.
FDA approval is a step toward paying the high price for aducanumab (brand name Aduhelm) through private insurance, Medicare, or Medicaid, but questions about coverage have yet to be answered. The Centers for Medicare & Medicaid (CMS) have not formally determined if the programs will pay for Aduhelm, meaning we don’t know yet whether Medicare or Medicaid will cover the drug. However, as an infusion drug that people with Alzheimer’s would need to take in their doctor’s office, aducanumab is likely covered by the outpatient care benefit under Medicare Part B, whose standard premium is $148.50 per month. Enrollees of Medicare Advantage, which pairs the government program with private insurers, also have a cap on expenses that would be significantly less than out-of-pocket costs for Aduhelm. Whether Medicare Part D, which pays for prescriptions, will cover Aduhelm has not been determined yet.
Whether private insurers will cover aducanumab (Aduhelm) remains to be seen and probably depends on the individual’s brain scans and a determination by medical professionals. Insurers will want to be as certain as possible that their customers will benefit from Aduhelm, and that probably means submission of MRI brain scans that show someone is a good candidate for the treatment. And depending on an individual’s plan, they might have to pay several thousand dollars before hitting their annual limit.
It’s also possible that insurers could reject a claim and not cover Aduhelm. Someone with advanced dementia, for example, might be considered a bad candidate for aducanumab because it’s been shown to help those in early stages.
In June 2021, it was announced that aducanumab (brand name Aduhelm) had been approved by the Food and Drug Administration under the “accelerated approval” designation, and the drugmaker Biogen said it expected Aduhelm to be available in more than 900 doctor’s offices beginning the same month.
Accelerated approval is for drugs that can help with serious illnesses but also need more study. Even though Aduhelm is available to people with Alzheimer’s disease whose doctors believe it will help (and can administer the infusions in their offices), another phase (Phase 4) of trials is ongoing. If there is not more evidence in this latest phase that aducanumab is effective for treating symptoms of dementia, the drug might be pulled off the market.
The road to get to this step, where Aduhelm can be prescribed and provided by doctors to people with Alzheimer’s disease, has been a roller coaster for the drug developer Biogen. At one point, the company fully declared that testing would end, and then changed its mind. Aducanumab made it to Phase 3 before an announcement 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.
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 said its results were promising, and FDA reviewers said 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.