Q. My family has a history of Alzheimer’s disease. We heard that a new drug for Alzheimer’s was just approved by the FDA. The process for its approval seemed kind of fast and it seems that Alzheimer’s drugs in the past have been unsuccessful. Could this one be different? Should people with Alzheimer’s and their families hope that there really is a drug that delays the start of the disease or slows its progression? Or should we manage expectations, based on nearly two decades of false starts? Thanks for your help!
A. On June 7, the U.S. Food and Drug Administration (FDA) approved the drug Aducanumab, made by the American pharmaceutical company Biogen in connection with the Japanese pharmaceutical company Eisai. The FDA approval of aducanumab marks a major milestone achievement in Alzheimer’s disease research. Aducanumab, which will be marketed and sold as Aduhelm, is the first new Alzheimer’s treatment in 18 years and the first and only that offers hope of actually attacking the disease process. Supporters believe that the approval of the drug is a reflection of the years of research and momentum we’ve seen in Alzheimer’s research. Problematically, the actual research is not clear.
Biogen and Eisai actually ended two major studies of the drug in 2019 after preliminary results suggested it did not work. However, a reanalysis of the data produced a more favorable result, and the companies decided to seek FDA approval after all. Essentially, the FDA was presented with one study showing the drug worked and another showing it didn’t, and the approval now granted by the FDA is quite controversial.
Aducanumab is intended to slow the cognitive decline that patients experience from Alzheimer’s. Clinical trial results show that the drug reduced the level of amyloid proteins from the brains of trial participants who had Alzheimer’s. Amyloid proteins are toxic proteins that are thought to be a biomarker of the disease. One thing both critics and supporters of approval agree on is that the drug substantially reduces levels of amyloid. The FDA said that the drug’s effect on a biomarker qualified it for the accelerated approval program.
“With such a devastating disease that affects tens of millions worldwide, today’s announcement is truly heartening in the fight against Alzheimer’s. This is the result of groundbreaking research and is a testament to Biogen’s steadfast determination to follow the science and do the right thing for patients,” said Michel Vounatsos, Chief Executive Officer at Biogen. “We are hopeful about the prospect of offering patients the first therapy to reduce the clinical decline of Alzheimer’s disease and the potential implication of these results for similar approaches targeting amyloid beta.”
What You Should Know About Aducanumab
Aducanumab will be made available as a treatment option for patients with mild memory problems. Here are some things you should know about aducanumab and its approval:
- Drug is administered via IV infusion: The drug, aducanumab, which will go by the brand name Aduhelm, is a monthly intravenous infusion intended to slow cognitive decline in people with mild memory and thinking problems. It is the first approved treatment to attack the disease process of Alzheimer’s instead of just addressing dementia symptoms.
- It was approved relatively quickly: Patient advocacy groups had lobbied vigorously for quick approval of aducanumab because there are so few treatments available for the debilitating condition. The FDA approved aducanumab to treat patients with Alzheimer’s using the Accelerated Approval pathway, under which the agency “approves a drug for a serious or life-threatening illness that may provide meaningful therapeutic benefit over existing treatments when the drug is shown to have an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients and there remains some uncertainty about the drug’s clinical benefit.” FDA further stated that “at the end of the day, we followed our usual course of action when making regulatory decisions in situations where the data are not straightforward.”
- Aducanumab will be available soon: Biogen is expecting to launch the drug quickly, with more than 600 sites across the country expected to administer it. Clinics for patients with cognitive problems have been scrambling to prepare.
- Reducing amyloid is not the same thing as slowing symptoms of dementia. Over more than two decades of clinical trials, many amyloid-reducing drugs failed to address symptoms, a history that, some experts say, made it especially important that aducanumab’s data be convincing.
- Approval was made despite opposition: The approval of the drug was a contentious decision made despite opposition from the agency’s independent advisory committee and some Alzheimer’s experts who said there was not enough evidence that the drug can help patients.
The 11-member advisory committee voted nearly unanimously in November that Biogen’s drug should not be approved, citing inconclusive evidence that the drug was effective.
- It was only tested on those with MCI and those who were in the early stages of Alzheimer’s: Although the clinical trials were conducted on specific populations of patients — those with mild cognitive impairment or early-stage Alzheimer’s whose brains contained higher-than-normal levels of amyloid — the FDA’s label for the drug does not contain any such restrictions. The label simply says the drug is “for the treatment of Alzheimer’s disease.”
- Safety risks are a concern: The risks with aducanumab involve brain swelling or bleeding experienced by about 40% of Phase 3 trial participants receiving the high dose. Most were either asymptomatic or had headaches, dizziness, or nausea. Such effects prompted 6% of high-dose recipients to discontinue. No Phase 3 participants died from the effects, but one safety trial participant did. Doctors have noted that similar side effects have occurred in trials of previous amyloid-lowering drugs, but doctors consider them manageable if a patient is evaluated regularly with brain scans.
- Another clinical trial is still needed: Evidence on whether the drug is effective in helping patients is incomplete. As part of its approval, the FDA is requiring Biogen to conduct another clinical trial to determine the effectiveness of the treatment. Alzheimer’s trials are challenging to conduct because it is often difficult to recruit enough participants. Because the condition can progress very gradually, trials need to be large and continue for many months in order to be able to see if a drug is slowing cognitive decline.
- Post-approval studies will also be needed: Additionally, “drug companies are required to conduct post-approval studies to verify the anticipated clinical benefit. These studies are known as phase 4 confirmatory trials. If the confirmatory trial does not verify the drug’s anticipated clinical benefit, FDA has regulatory procedures in place that could lead to removing the drug from the market.” Several experts expressed skepticism that Biogen would be able to recruit many participants in the United States for a post-market trial because patients who can get a drug from their doctors are often reluctant to take the chance of receiving a placebo in a clinical trial.
- Aducanumab will be expensive: Biogen, its manufacturer, announced Monday afternoon that the list price would be $56,000 a year. In addition, there will most likely be tens of thousands of dollars in costs for diagnostic testing and brain imaging. The company is expected to make billions of dollars from the treatment. Because Alzheimer’s primarily affects older people, most costs are expected to fall to Medicare’s Part B program. Medicare has not yet said how it would cover the drug and its associated costs.
Are There Other Medications that Delay Alzheimer’s?
Currently, five medications approved in the United States can delay cognitive decline for several months in various Alzheimer’s stages. Some other drugs in clinical trials are promising, but they are most likely three or four years away from potential approval.
Another promising new drug, called ALZ-801, from Alzheon, is ready for Phase 3 trials. ALZ-801 works differently than aducanumab. It targets specific toxins called oligomers, which build up in the brain and are believed to lead to plaque formation. ALZ-801 is also easy for patients to take. It’s a small tablet, so it can be taken by mouth at home, versus Biogen’s aducanumab, which requires intravenous delivery in a clinic or physician’s office. Read more about ALZ-801 here.
When it comes to future drugs, some scientists worry that aducanumab’s approval could lower standards, allowing them onto the market before experts in the field are convinced the benefits outweigh any safety risks.
Not ready to rush out for Alzheimer’s drug just yet?
Many scientists, doctors, and patients are cautiously optimistic about aducanumab. Despite the FDA approval, they believe that more studies are needed and post-approval data needs to be collected and analyzed. We will continue to share updates and more information about this and other Alzheimer’s drugs in the future!
Planning for a Loved One with Alzheimer’s
Do you have a loved one who suffers from Alzheimer’s or another form of dementia? Persons with Alzheimer’s disease and their families face special legal and financial needs. At the Farr Law Firm, we are dedicated to easing the financial and emotional burden on those suffering from Alzheimer’s and their loved ones. Through the process of Life Care Planning and Medicaid Planning (also called Medicaid Asset Protection Planning), we help protect a family’s hard-earned assets while maintaining your loved one’s comfort, dignity, and quality of life by ensuring eligibility for critical government benefits such as Medicaid and Veterans Aid and Attendance. If your family is facing a diagnosis of Alzheimer’s disease or any other type of dementia, please call us as soon as possible to make an appointment for an initial consultation:
About Evan H Farr, CELA, CAP
