• Nondiah Khalayi

What You Need to Know About the Recent Approval of an Alzheimer's Drug

On June 7, 2021, the Food and Drug Administration (F.D.A.) issued accelerated approval to Biogen's new Alzheimer's drug aducanumab marketed as Aduhelm, the first in 18 years. The approval sparked hope in more than 6 million Americans and 30 million people around the globe with the disease and other dementias.



Aduhelm single-dose injection.
Aduhelm single-dose injection. (Susan Mathews)

The approval has also sparked a contentious debate from the public, policymakers, and dementia patients over whether the drug is effective.

Alzheimer's is the sixth-leading cause of death in the U.S., and C.D.C. estimates that the numbers could double in the coming decades.


In this article, we will talk about:


What is Alzheimer's Disease?

Why has it taken 18 years?

What is Accelerated Approval?

The Issues Underlying the Approval of Aduhelm

- the debate

- members of the FDA advisory board resign

- the cost - expensive yet uncertain

How the drug works

- eligibility criteria

- how is Aduhelm taken?

- but does Aduhelm work?

Final thoughts


Let's get started!


What is Alzheimer's Disease?


Alzheimer's is a progressive type of dementia that affects memory, thinking, and behavior.

Memory problems are the main symptom of Alzheimer's disease.


Centers for Disease Control and Prevention highlights the following as other symptoms of Alzheimer's,

  • Memory loss disrupts daily life, such as getting lost in a familiar place or repeating questions.

  • Trouble handling money and paying bills.

  • Difficulty completing routine tasks at home, at work, or leisure.

  • Decreased or poor judgment.

  • Misplacing things and being unable to retrace steps to find them.

  • Changes in mood, personality, or behavior


Alzheimer's gets worse with age. People ages 60 and above are at risk of developing Alzheimer's.


Genetics plays a role in developing Alzheimer's disease. However, if one adopts healthy lifestyle behaviors such as enough physical exercise, seeking help, limited consumption of alcohol, and a nutritious diet, their risk of developing Alzheimer's may reduce.


At the moment, there is no definite cure for Alzheimer's, but it can be managed.


Medical management of Alzheimer's aims to maintain brain health, manage behavioral symptoms, and delay the severe symptoms of the disease, such as the inability to recognize close family and friends.


Sadly, the available treatment options do not work for everyone.

Why has it taken 18 years?


The last time the F.D.A. approved a drug for this devastating disease was in 2003 - the year in which Forest Labs' Namenda was approved in the U.S.


Alzheimer's patients and their families have waited for 18 years for a new approval of Alzheimer's disease.


But why 18 years? Yet other diseases have a diverse pool of treatment options available.


Most drugs have failed in clinical testing over the years. For example, Johnson & Johnson's Atabecestat halted its mid-stage trial in May 2018 due to safety issues.


In other cases, Alzheimer's drug candidates have proved inefficient throughout the clinical trial stages. This has happened for 18 years.


One probable reason for the low success rate in establishing drugs for this nefarious disease is that scientists don't fully understand its complex nature.

What is Accelerated Approval


The U.S. federal law allows accelerated approval of a drug intended for a severe disease when it is expected to offer a meaningful advantage over available treatments. It is used in times when there is uncertainty about the potential clinical benefits of a drug.


The law states that a drug may be approved when it is "reasonably likely" that its capacity to improve a measure of disease predicts clinical benefit. Reasonably likely denotes a level of uncertainty.


Therefore, in Aduhelm's case, the data presented met the accelerated approval standard because of the uncertainties of its clinical benefit.


Past accelerated approvals of cancer drugs affirmed the accelerated approval of Aduhelm. In most cases, there have been positive results in accelerated approvals of cancer drugs.

If Aduhelm does not prove any clinical benefit to Alzheimer's patients, the F.D.A. shall start working to remove the drug from the public.

The Issues Underlying the Approval of Aduhelm


The Debate

As much as there are still uncertainties regarding its efficiency, most Alzheimer's patients and their families are hopeful that the recent approval of the Aduhelm drug shall help manage the intractable condition.


The medical research fraternity has been met with differing opinions. Some say it will make a significant difference, while others say that its effectiveness is questionable and its approval was controversial.

Members of the FDA Advisory Board Resign

Following the approval of Biogen's Aduhelm, Mayo Clinic neurologist, Dr. David Knopman, resigned. He was a panel member and investigator in the clinical trials of Aduhelm before its approval and had been recused from a November 2020 meeting to review the drug.


Dr. Knopman did not participate in the vote because the F.D.A. did not consider the advisory panel's thoughts on the inconclusive evidence that the drug was effective.


Dr. Joel Perlmutter, a Washington University neurologist, resigned from the committee, citing that F.D.A.'s approval of Aduhelm mocked the committee's consultative process.


Aaron Kesselheim, a professor of medicine at Harvard Medical School and Brigham and Women's Hospital, who had served the F.D.A. committee for six years, also resigned.


He noted that "This might be the worst approval decision that the F.D.A. has made that I can remember."


The three former F.D.A. panelists, along with several researchers, citing that the drug might cause more problems for Alzheimer's patients than solve them.

The Cost - Expensive yet Uncertain

Aduhelm drug is stipulated to be very costly and, in turn, less affordable to patients.


Biogen Inc. will charge around US$56,000 per year per person for the drug. This is rather costly and would attract a revenue of nearly $17 billion per year if 5% of 6 million people with Alzheimer's in the U.S. receive the treatment.

The issue here is not that Aduhelm is expensive but has uncertain benefits and may be unsafe for use.

How the drug works


Aduhelm drug's approval is the first novel treatment of Alzheimer's that aims at treating a possible cause of the disease rather than just the symptoms. Previous medications for Alzheimer's have been treating symptoms of the disease.


Aduhelm clears out the buildup of beta-amyloid plaques in the brain that disrupt the communication of neurons.

The F.D.A. approved Aduhelm because of its ability to reduce the beta-amyloid plaques and potentially slow down memory loss and function that is often impossible to address in Alzheimer's disease.

Eligibility Criteria

People with early-stage Alzheimer's disease are potentially eligible for Aduhelm. However, beyond this stage, Aduhelm may not be effective.

How is Aduhelm taken?

To take Aduhelm, one needs an intravenous infusion every four weeks - for the rest of their lives.


But does Aduhelm work?

One thing about accelerated approval drugs is that the company in question, in this case, Biogen, should conduct an additional study to check if Aduhelm works.


Clinical studies show that 30% of those who took the drug had reversible brain swelling, while 10% had tiny brain bleeds. Other side effects are not known, more reason to be skeptical about the medicine.


For now, there is no definite information whether Aduhelm will work or not - until results from an additional study that could take three to four years are out.


In the meantime, the devastating effects of Alzheimer's disease and the dire need of patients and families of the intractable disease, alongside other vital factors, have necessitated the F.D.A. approval of the drug.

Final Thoughts


While there are varied thoughts regarding Aduhelm, it is important to stay hopeful that the drug helps manage Alzheimer's disease.


There is no doubt that Aduhelm's approval has and will bring in more research in Alzheimer's disease and other dementias. In addition, it may be a pathway to discovering better treatment options for this degenerative disease, even if it proves ineffective after Biogen conducts future trials.


Other FDA-approved medications for Alzheimer's are helpful if one cannot afford Aduhelm (once Biogen starts distributing it) or does not meet the eligibility criteria.


Also, the US Government is discussing whether to add Aduhelm and other related drugs to the Medicare scheme.


An old lady enjoying the naked sky with a doctor.


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References


https://www.alz.org/alzheimers-dementia/what-is-alzheimers


https://www.bloombergquint.com/onweb/harvard-expert-quits-fda-panel-as-furor-over-biogen-drug-grows


https://www.cdc.gov/aging/aginginfo/alzheimers.htm


https://edition.cnn.com/2021/06/17/opinions/biogen-alzheimers-drug-opinion-ramachandra-ross/index.html


https://www.health.harvard.edu/blog/a-new-alzheimers-drug-has-been-approved-but-should-you-take-it-202106082483


https://markets.businessinsider.com/news/stocks/remember-when-was-the-last-time-a-new-alzheimer-s-drug-was-approved-1027337782


https://www.nature.com/articles/d41586-021-01546-2


https://www.reuters.com/world/us/two-members-us-fda-advisory-panel-resign-over-alzheimers-drug-approval-2021-06-09/


https://techcrunch.com/2021/06/07/after-contentious-debate-fda-approves-first-alzheimers-drug-since-2003/


https://www.washingtonpost.com/opinions/2021/06/23/fda-alzheimers-drug-approval-aducanumab/



Nondiah Khalayi is a Kenya-based Statistics and Programming student at Kenyatta University, a Health Science student at the University of the People, and also a Content Writer at IYOPS. Being an INFJ-T personality, she enjoys a calm life, coding, data analysis, reading, and writing multiple-niche research-based articles.


Inputs and Edits by Sovena Ngeth and Aswin Raghav R.