Will The Fda Limit Who Can Be Treated With These Therapies
The FDA initially approved aducanumab for anyone with Alzheimers a disease that affects more than six million people in the United States. But Biogen tested the antibody only in a subset of these patients.
After the backlash, the agency narrowed the specification to people with mild cognitive impairment or mild dementia stage, to better match the group tested in Biogens trials. But the drugs label, which specifies who should use it, does not stipulate that people must have evidence of amyloid build-up in their brain a key requirement for inclusion in Alzheimers trials.
Uk Regulators Are Assessing The Data Right Now
The UK and European regulators are currently completing their own rigorous assessment of the data around aducanumab and are expected to announce their response in the autumn.
Regulators decide whether a drug is safe and effective. However, this is only the first step towards the drug reaching people in the NHS. The health services then needs to decide if it will fund a medicine. Aducanumab would need to be assessed by NICE and the Scottish Medicines Consortium to determine its cost-effectiveness for the health service and therefore whether it is funded for routine use in the NHS. This process looks at the cost of the medicine and also the financial impact it would have on NHS services against the clinical benefit of the medicine, For Aducanumab we dont expect the process to finish until the middle of next year at the earliest.
Until the outcome of those decisions, the drug wont be available to NHS patients.
Watch our animation to find out more about this process.
We know from recent experience with COVID-19 vaccines that its possible to speed up this process without compromising on the quality of the assessment. So today, our Chief Executive Hilary Evans has to ask the government to prioritise and accelerate this process, so that people with Alzheimers in the UK can be given the answers they need as quickly as possible.
Am I Eligible To Receive Aducanumab
The clinical trials of aducanumab studied a limited, specific group of people. You may be eligible to receive the drug if you:
- Are younger than 85 years old
- Have confirmed mild cognitive impairment, defined as a mild decrease in memory and/or thinking that occurs daily but does not yet affect functioning
- Have amyloid present in the brain
- Do not have a history of microbleeds, transient ischemic attacks, or stroke due to bleeding
- Do not take blood-thinning medications
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What Are The Possible Side Effects Of Aducanumab
The most common side effects include areas of brain swelling, small brain bleeding, headache, or falls. The areas of brain swelling and small brain bleeding are usually temporary and resolve over time. Everyone who receives aducanumab will have periodic MRIs to monitor for these side effects, which can cause headache, confusion, dizziness, vision changes, or nausea but may not cause any symptoms.
Who Is A Candidate For Aducanumab
Based upon the clinical trials in which it was studied, the drug can be potentially considered for use in individuals with early-stage Alzheimers disease. This means individuals who have Alzheimers in its mild cognitive impairment or mild dementia stage. Individuals in this early stage of Alzheimers may be able to function normally, or they may require a little bit of help with complicated activities like paying bills, grocery shopping, preparing meals, or balancing their checkbook. Individuals who need help with dressing, bathing, or other basic activities would be beyond the early stage and the drug would not be indicated for them.
Note that not everyone with mild cognitive impairment or mild dementia has Alzheimers disease. There are other causes of these problems as well. To determine if Alzheimers is present, you need to get either an amyloid PET scan or a lumbar puncture to be sure you have the amyloid plaques of Alzheimers. Currently, a lumbar puncture is generally covered by insurance, but an amyloid PET scan is not.
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Discuss With Your Doctor
Should you or a loved one take aducanumab? You should discuss this decision with your doctor. Because we dont know if aducanumab works or not, deciding to take it is similar to deciding to participate in a clinical trial. As mentioned above, the known side effects are that 30% of people experienced reversible brain swelling and more than 10% had tiny brain bleeds. Although it does clear amyloid plaques from the brain, we dont know if it will slow down the dementia or not.
What Everyone Can Do Today
I am hopeful that this medication will work to slow Alzheimers and reduce the suffering it causes individuals and their families. We should remember that the other FDA-approved medications for Alzheimers can also be helpful , as can , engaging in aerobic exercise, eating a Mediterranean , staying , keeping a positive attitude, and using memory strategies.
About the Author
Andrew E. Budson, MD, Contributor
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A New Treatment For Alzheimers Disease
Improving cognition in Alzheimers disease
Magnetic stimulation of the brain shows promise as a potential new treatment for people with Alzheimers disease and is now ready for testing in larger clinical trials.
- Professor Kate Hoy of the Bionics Institute has developed a treatment program using Transcranial Magnetic Stimulation to improve brain function in people with Alzheimers disease.
- Alzheimers disease has been shown to interfere with important networks in the brain and this disruption in neural communication is linked to the cognitive difficulties experienced.
- Our team will conduct a large-scale, randomised, controlled trial of a personalised treatment approach, which will include using neuroimaging to precisely identify the regions of the brain to stimulate for each patient, and to adapt the TMS for each patient so that stimulation is delivered in a manner which matches their own brain activity.
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The findings raise hopes that aiming not so narrowly at beta-amyloid, and instead at the full cascade of molecular changes, might be more effective. But this hypothesis-free approach can also be a bit unsettling. Sure, it looks like the drug might work for Alzheimers disease. But why would it work? No one knows.
The mechanism of the drug is well-known, but what the authors havent addressed is how that mechanism is related to what they think might happen if they were to give this drug to Alzheimers patients, said Shilpa Kadam, a neurologist at Johns Hopkins University who studies developmental disabilities. She has been closely following a trend of physicians prescribing bumetanide off-label to people with autism, epilepsy, and other brain disorders. But in these instances of drug repurposing, the mechanism for why the drug might provide a benefit is well-understood. Bumetanide reduces water retention by blocking proteins that shuttle salts across cell membranes. Those proteins are also found in neurons, and if those neurons are overexcited as occurs in conditions like epilepsy blocking them can restore balance.
However, bumetanide can also be tricky to use because it can leave patients dehydrated and with their electrolytes off-kilter, said Jeffrey Cummings, director of the Chambers-Grundy Center for Transformative Neuroscience at the University of Nevada Las Vegas, who was not involved in the study.
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Medicare Will Only Cover New Alzheimers Drug In Trials
April 8, 2022 — Federal officials have made their final decision: Medicare will only pay for patients to get the new Alzheimer’s drug aducanumab if the patients are participating in clinical trials.
On Thursday, the Centers for Medicare & Medicaid Services released its national coverage determination for aducanumab and other similar drugs that target beta-amyloid in the brain, which is considered a hallmark of Alzheimer’s disease.
In a press release, the CMS said its decision is a two-part policy based on the currently available evidence for anti-amyloid agents.
Last year, the FDA approved aducanumab for Alzheimerâs disease using the accelerated approval pathway, because trials had shown the drug removed beta-amyloid from the brain, but it wasnât clear the drug had improved the symptoms of people with Alzheimerâs.
The decision sparked controversy and led to the resignation of three members of the FDA’s advisory panel that had voted against approving the drug.
CMS set far less restrictive conditions for potential coverage of anti-amyloid drugs that may get full FDA approval in the future. In such cases, coverage would be pegged to participation in CMS-approved studies, such as a data collection through routine clinical practice or registries, not only clinical trials.
Howard Fillit, MD, co-founder and Chief Science Officer of the Alzheimerâs Drug Discovery Foundation, supported the decision.
Show Sources
Biogen.
What We Know So Far
The studys Chief Investigator Professor Naji Tabet of Brighton and Sussex Medical School said:
Results of the phase 1 and phase 2 trials indicate that semaglutide may have a positive effect on Alzheimers disease, but this phase 3 trial will give us a more accurate picture.
We will measure the impact by comparing cognition tests taken at the start and end of the study and by collecting regular information about our patients health, cognition, ability to perform daily activities and general wellbeing.
I would encourage anyone with early Alzheimers disease or MCI to consider taking part in this study.
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How Does Aducanumab Work
Amyloid is a protein that can build up in the brain and may cause Alzheimers disease. Aducanumab travels to the brain, sticks to amyloid, and removes it.
You may be eligible to participate in clinical research studying aducanumab or other drugs that could fight Alzheimers disease and other types of dementia.
Early Stage Smaller Trials
After initial trials showed that Aducanumab was safe to use in humans, a further trial called PRIME assessed if the drug could slow the progression of Alzheimers disease in people who were in the early stages of the disease. This included people who had mild cognitive impairment or early-stage dementia.
The PRIME trial started in 2012. Biogen, the pharmaceutical company who developed the drug, reported that treatment led to a reduction in amyloid levels in the brain. The company said the drug appeared to slow the rate of cognitive decline for people with mild Alzheimers disease receiving the drug.
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Large And Longer Trials
These findings allowed Biogen to conduct larger clinical trials of Aducanumab. Two trials, called ENGAGE and EMERGE, collectively enrolled over 2,500 people with MCI or early-stage dementia caused by Alzheimers disease.
The changes in the brain caused by Alzheimers disease tend to start many years before symptoms show. This means that earlier treatment is likely to have a better chance of being effective. The main aim of the ENGAGE and EMERGE trials was to see if Aducanumab could reduce signs of cognitive decline in the people with MCI and mild dementia. Participants received different doses of the drug and were compared to people receiving a placebo treatment. The placebo contained no active ingredient.
The two large Aducanumab trials began in 2015 but were cut short in March 2019. Although the EMERGE trial was said to be trending positive in terms of potential outcomes, early results indicated the ENGAGE study was not going to be successful. In order to progress, Biogen had specified that both trials needed to be heading in the right direction. The results meant that both trials were terminated.
Can Exercise Prevent Alzheimer’s
Since new pharmaceutical treatments may be years from being available for patients, some Alzheimers researchers are looking more to early detection and prevention such as exercise to slow the onset or progression of the disease.
Data from the longest-ever phase 3 trial of exercise on cognition released at the conference on Tuesday found that exercise may stall cognitive decline in Alzheimers patients.
Three hundred patients in the trial by Alzheimers Disease Cooperative Study in partnership with Wake Forest and the YMCA were randomized to moderate intensity aerobic training, or to stretching, balance and range of motion for 18 months. Neither group showed 12-month declines in cognitive tests.
The data suggest exercise “may be a mechanism of potentially reducing risk for not only developing dementia” but “an overall healthy, balanced lifestyle approach to risk reduction,” said Edelmayer, of the Alzheimers Association.
A key benefit of an exercise program is that doctors could prescribe it to patients right away to reduce their risk of the disease, without waiting years for clinical drug trials.
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How Will Aducanumab Impact The Future Of Alzheimers Care
I think its going to herald a new era in Alzheimers therapy. There are now two other monoclonal antibodies for treating Alzheimers lecanemab and donanemab that are showing similar promise in early studies. In the next two to three years, as more clinical-trial results are published, a lot of the controversy and smoke around these drugs should clear. We will have a clearer picture of what these drugs do, who they help, and who they dont help.
Consider the history of treatment for HIV and many cancers. The first drugs that were used to treat these diseases had serious toxicity and modest benefit a lot like aducanumab. Yet we now have highly effective drug cocktails that allow people with HIV to live normal lives and keep the virus under control, and we have extremely sophisticated ways of understanding individual tumors and developing targeted therapies to treat them. With Alzheimers, we have just reached the precipice of this precision approach to treatment, and aducanumab is the first drug, hopefully, of many.
I wish it were a better drug. I wish it were less controversial. But I do think its a step in the right direction.
Disclosures: UCSF served as an enrollment site for the clinical trials of aducanumab. Gil Rabinovici was not involved in the trials. He has done consulting work unrelated to aducanumab for Eisai Co. Ltd., which has a partnership with Biogen Inc. to develop and commercialize aducanumab and other treatments for Alzheimers disease.
How Did The Drug Become Controversial
In February 2019, the manufacturer, Biogen, suddenly announced that they had stopped the phase III trials of aducanumab, which were designed to test whether the drug slowed cognitive decline for patients with amyloid plaques who were in the early stages of memory loss. Basically, Biogens statisticians had determined that there was a very low likelihood that the drug would show a difference in clinical outcomes compared with a placebo.
Then, eight months later, the company made another sudden announcement: As more of the trial data had become available, they had found that one of the trials in which more people received the highest dose of the drug actually was successful. In the following months, Biogen worked closely with the FDA to try to understand these very complicated data. There are now allegations that this relationship was a little too close at least two congressional committees and the Office of the Inspector General are investigating.
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But Does The Drug Work
In a I reviewed the publicly available data and the daylong FDA hearing on aducanumab. In a nutshell, there were two large clinical trials to assess effectiveness, side effects, safety, and how the drug might be used in clinical practice. One of the studies was positive, meaning that the drug worked to slow down the decline of thinking, memory, and function that is usually impossible to stop in Alzheimers. The other large study was negative. In my view and that of the FDA advisory panel these results mean that we dont know if the drug works or not.
Another factor to consider is that the potential benefit if the drug works as well as it did in the positive study was fairly small. Looking at the two objective measures, in the positive trial, the high dose made a 0.6-point change on the 30-point Mini-Mental State Examination. On the 85-point Alzheimers Disease Assessment ScaleCognitive Subscale-13, the high dose made a 1.4-point change.
How Can I Find Out More About How To Receive Aducanumab
If you are already being treated for mild cognitive impairment or Alzheimers at Duke, talk to your doctor at your next, regularly scheduled appointment. If you dont have an appointment scheduled, contact your doctor via MyChart. If you are not an existing Duke patient, ask your primary care provider, neurologist, or memory disorder specialist for a referral to one of our Alzheimer providers.
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Other Experts Disagree With You Including Some Of Your Own Ucsf Colleagues Who Are Not Convinced There Is Enough Evidence That Aducanumab Can Help People
I agree that this is not a home-run drug, I agree that the data could be clearer, and I can understand physicians who are worried and reluctant. I wish the FDA had required Biogen to complete a third phase III trial with the higher dose so that there wouldnt be any confusion about whether the drug does or doesnt work.
That being said, Im not ready to throw this drug out entirely now that the FDA has approved it. Alzheimers disease is a devastating illness. Given the choice between the certainty of decline and the chance that a drug like this might slow that process even if the benefit is modest, and there is risk involved many patients will choose to take that risk. I feel we have an obligation to discuss this drug as an option with our patients who might benefit.