On June 7, 2021, the Food and Drug Administration (FDA) approved the drug Aduhelm (aducanumab) for the treatment of Alzheimer’s disease. This approval was a monumental and controversial decision. The Penn Memory Center has received many questions from patients and families about the decision and the drug.
The Penn Memory Center is committed to answering these questions and providing the community with accurate and updated information regarding Aduhelm. We will attend to the nuance, certainties, and uncertainties.
On this page are questions from patients and families and clinical team’s answers as well as a recording of the PMC Community Discussion about Aduhelm held on June 16, 2021 led by PMC Co-Directors Jason Karlawish, MD, and David Wolk, MD.
For specific questions regarding your condition or the condition of a loved one, please contact your physician or make an appointment with the clinicians at the Penn Memory Center. For other questions not answered here, please use our contact form or email firstname.lastname@example.org.
On April 7, 2022, the Centers for Medicare and Medicaid Services (CMS) released a decision for Medicare coverage of Aduhelm (aducanumab). CMS will cover Aduhelm under coverage with evidence development (CED). This means Aduhelm is covered for those who are participating in clinical trials.
- Medicare Officially Limits Coverage of Aduhelm to Patients in Clinical Trials (4/7/2022)
- On Aduhelm, Medicare Agency Gets Pressure From All Sides (2/18/2022)
- European Regulators Turn Down Aduhelm; Trial Plans Announced (12/17/2021)
- As Medicare Decides Whether to Pay For Aduhelm to Treat Alzheimer’s Disease, Its Future is Uncertain (12/3/2021)
See our Aduhelm news archive at the bottom of the page.
What is Aduhelm (aducanumab)?
Aducanumab is a drug developed by Boston-based biotechnology company Biogen. Studies of it have been designed to test whether is slows the progression of Alzheimer’s disease. Aducanumab is the scientific name of the drug. It is marketed as Aduhelm.
How does Aduhelm work?
Patients with Alzheimer’s disease have a build-up of a particular protein, amyloid-beta, in their brain. This leads to the degeneration of neurons. Aducanumab is a human monoclonal antibody synthesized in a laboratory that selectively targets these amyloid-beta plaques.
Studies show that aducanumab does not stop or reverse the disease, but may slow progression. Clinical trials have shown evidence of a significant reduction in the build-up of amyloid-beta plaque in the brain.
How will Aduhelm be administered?
The drug will be given as an hour-long intravenous (IV) infusion every four weeks.
How much does Aduhelm cost?
The drug originally cost $56,000 per year per person, or ~$4,600 per infusion. In January of 2022, Biogen cut the price in half, making the drug $28,200 per year per person. Additional costs such as, but not limited to, amyloid PET and MRI scans and related blood tests are not included in the cost.
The Centers for Medicare and Medicaid Services (CMS) will cover Aduhelm under coverage with evidence development (CED). This means Aduhelm is covered for those who are participating in a clinical trial.
Will physicians at the Penn Memory Center prescribe Aduhelm?
After discussing the risks and uncertainties, physicians at the Penn Memory Center will prescribe Aduhelm to patients and family who are interested and eligible to receive it.
“I conceive of Alzheimer’s disease as a disease that goes after a person’s autonomy and their ability to self-determine their life, early and relentlessly,” PMC Co-Director Dr. Jason Karlawish said.* “So, if — after a deliberate and introspective discussion with the patient and their family about the drug, its uncertainties, the side effects, cost, and other factors — a patient and their family decide they want to take it, I will prescribe it.”
“One has to weigh the potential, but certainly unknown, benefits of the drug with the known side effects. In essence, that is what people consider when entering a clinical trial. The difference here is that this is now clinical practice,” PMC Co-Director Dr. Wolk reiterated.
Who will be eligible for Aduhelm?
Individuals with mild cognitive impairment (MCI) or mild-stage dementia due to Alzheimer’s disease are eligible to receive Aduhelm.
Patients will need to contact their physician or make an appointment with the clinicians at PMC to discuss specific health conditions and situations.
Is Aduhelm available at the Penn Memory Center?
The Penn Memory Center does not administer Aduhelm to patients. To receive the drug, you must be enrolled in a research study. The Penn Memory Center plans to be a site for future Aduhelm clinical trials, such as the ENVISION study.
When would a patient begin to show improvement after using Aduhelm?
The studies show that Aduhelm does not stop or reverse the progression of the disease, but may slow the progression of disease. The effects of the drug are shown over the course of many months.
How does Aduhelm react with other available drugs for Alzheimer’s disease (memantine and cholinesterase inhibitors)?
There have been no harmful interactions between Aduhelm and other drugs prescribed for Alzheimer’s disease. This is based on data from a few thousand people, and so rare risks and drug-drug interactions may not be discovered until more patients use it for longer periods of time.
What is the effect of the drug on short-term memory?
Aduhelm does not improve cognitive abilities or reverse the progress of cognitive impairment and dementia. This class of drugs are designed to slow the progression of disease rather than to provide symptomatic benefit.
What is the history of Aduhelm?
To study Aduhelm, Biogen sponsored several trials. In 2016, Biogen reported that aducanumab became a part of the FDA’s Fast Track program, intended to develop “new treatments for serious conditions with an unmet medical need.”
The efficacy of Aduhelm was investigated in two clinical trials – EMBARK and EMERGE.
In March 2019, Biogen announced that that the Phase 3 trials, along with a Phase 2 and Phase 1B trial, were to be discontinued as the drug had not a passed a futility analysis required to prove that it could achieve positive results. However, in October of the same year, Biogen revealed that of the two phase 3 trials – EMBARK and EMERGE – the latter had met its primary endpoint and showed successful results in slowing down amyloid buildup in the brains of participants.
In 2020, Biogen filed for FDA approval. A few months later, in November, the FDA’s independent Peripheral and Central Nervous System Drugs Advisory Committee examined available data. The committee, consisting of eleven medical and neurological experts, advised against the approval of the drug as there was not enough evidence to support the drug as a safe and effective treatment. Read more about the advisory committee’s meeting last November and PMC’s involvement.
“I do think it’s important to appreciate the context of what’s happened here,” Dr. Wolk said. In the duration of his professional research and clinical career, Aduhelm is the first Alzheimer’s disease drug to be approved by the FDA. The last drug was Namenda (memantine) in 2003. “The mere fact that we have developed tools where we can actually see the amyloid plaques of Alzheimer’s disease as well as the tangles, and developed immune-based drugs to remove or target amyloid in the brain is remarkable. I think this is a hopeful time and I don’t want that to get lost.”
Was the Penn Memory Center a part of any of the studies and clinical trials for Aduhelm?
Yes. PMC has had an active role in the Aduhelm trials through participation in the EMERGE trial and the EMBARK Study. The latter study was designed to evaluate the long-term effects of the drug at a high dose. Dr. David Wolk was the site principal investigator for the trials at Penn. More information can be found about PMC’s EMBARK trial and PMC’s involvement with aduhelm. PMC also plans to be a testing site for for ENVISION, the study to verify the clinical benefit of Aduhelm.
Is the Penn Memory Center a part of trials studying other Alzheimer’s disease drugs?
The Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) Study at PMC investigates solanezumab, a drug by the Eli Lilly and Company, as a monoclonal antibody that could reduce the impact of the amyloid-beta protein in the brain. The study is not enrolling for new participants. Learn more about the A4 Study.
The AHEAD study at PMC is currently studying the effect of the drug lecanemab, a human antibody that binds to amyloid proteins in the brain, in reducing the risk of developing dementia. The study is currently enrolling. Learn more about the AHEAD Study.
Is Aduhelm (aducanumab) FDA-approved?
Aduhelm (aducanumab) was approved by the Food and Drug Administration (FDA) on June 7, 2021.
FDA approved the drug using its Accelerated Approval Pathway. This allows the Agency to approve drugs that could be “potentially valuable therapies for patients with serious diseases where there is an unmet need, and where there is an expectation of clinical benefit despite some residual uncertainty regarding that benefit.”
A notable condition of the approval requires Biogen to conduct a new, randomized, controlled, clinical trial to verify the drug’s clinical benefit. Biogen has not yet announced when this trial will start. The FDA has given Biogen until 2029 to complete the new clinical trial. Learn more about the Accelerated Approval Pathway in the video below.
Why did the FDA approve Aduhelm?
According to Dr. Patrizia Cavazzoni, director of the FDA Center for Drug Evaluation and Research, the FDA believed that there was “substantial evidence that Aduhelm reduces amyloid beta plaques in the brain and that the reduction in these plaques is reasonably likely to predict important benefits to patients.”
What were the reactions from the scientific and medical community to the FDA approval of Aduhelm?
Co-directors of the Penn Memory Center Drs. Dave Wolk and Jason Karlawish, among other scientific and medical experts, believe that the data provided by the Biogen trials does not sufficiently support that Aduhelm is a safe and effective treatment.
“Immune-based drugs that target the amyloid-beta plaques in the brain have shown some promise in clearing amyloid from the brain and several drugs that do so with similar effect to aducunamab have also shown signal for slowing disease progression or downstream markers of disease progress,” Dr. Wolk said. “So, I think this approach to treatment of Alzheimer’s disease and other dementias is certainly not off the table. Aducanumab falls into that bin of treatments that show some promise but, right now, there remains uncertainty about their effectiveness.”
In the wake the FDA approval, three members of the advisory committee have resigned.
What is the evidence in support of aducanumab?
In a press release on June 7, 2021, Biogen stated, “In these studies, ADUHELM consistently showed a dose- and time-dependent effect on the lowering of amyloid beta plaques.”
Biogen also reported, in 2019, that the Phase 3 EMERGE trial “met its primary endpoint showing a significant reduction in clinical decline.”
What are the side effects of Aduhelm?
The main side effect of Aduhelm is ARIA (Amyloid-Related Imaging Abnormalities). These are abnormalities caused by inflammation around blood vessels that can lead to local swelling of the brain and microhemorrhages in the brain. For the most part, ARIA is asymptomatic, but about 25% of these individuals have mild symptoms and a small number have more serious and permanent neurological outcomes. Additional side effects include hypersensitivity reactions, headaches, diarrhea and falls.
According to Dr. Jason Karlawish, another unusual risk is that the drug might not have any benefit. “It gets back to the FDA’s point that another study is required to confirm the benefit of the drug,” he said. “The point that clinicians and researchers like myself have raised is there needs to be one more study done to show that this drug can benefit patients. Currently, patients and their families will be undertaking a difficult cognitive exercise debating the merits of taking a drug that might not benefit.”
Will Penn be participating in a Phase 4 trial for Aduhelm?
The Penn Memory Center plans to be involved with the Phase 4 trials for Aduhelm that will verify the clinical benefit of the drug. These trials are called ENVISION. We are still involved in the EMBARK study which is an open-label follow-up study in individuals who have participated in prior aducumab studies.
I was/am a participant in the clinical trials for aducanumab. Is there anything I should know?
Please connect with your research team for further information.
- Aduhelm Lowers Tau: Registry to Track Real-World Performance (11/19/2021)
- Mass General Brigham won’t offer Biogen’s new Alzheimer’s drug (9/29/2021)
- An open letter to the Alzheimer’s disease community from Biogen Head of Research and Development, Alfred Sandrock, MD, PhD (7/22/2021)
- Cleveland Clinic, Mount Sinai and Providence Won’t Give Biogen’s New Alzheimer’s Drug (7/15/2021)
- Medicare Is Deciding Now Whether To Cover Aduhelm—And All the Similar Drugs to Follow (7/13/2021)
- FDA commissioner calls for review of Aduhelm approval (7/9/2021)
- Actual cost of Aduhelm may be over $61,000 (7/9/2021)
- FDA revises label, reduces number of people eligible to two-thirds (7/8/2021)
- House Committees launch investigation into pricing and approval of Aduhelm (6/25/2021)
*Quotes have been edited for clarity.