FDA Approval of Aduhelm (Aducanumab) for Alzheimer's Disease

Alzheimer’s disease is the most common form of dementia. Over time, Alzheimer’s can lead to a slow decline in memory, thinking, reasoning skills, ability to carry out daily activities such as getting dressed, social interactions, and simply having a conversation with loved ones and friends. Currently there approximately 6 million people in the US living with Alzheimer’s.

On June 7, 2021 the FDA approved Aduhelm (aducanumab) for the treatment of Alzheimer’s. The first new treatment in over 17 years, its approval has not come without controversy.

There is no cure for Alzheimer’s. However, there are FDA-approved medications that can keep the symptoms from getting worse for a period of time. These medications include:

Aricept (Donepezil)

Exelon (Rivastigmine)

Razadyne (Galantamine)

Namenda (Memantine)

Aduhelm (Aducanumab) *Newly approved*

An Alzheimer’s diagnosis is made through cognitive testing, CT, MRI, and PET scans. Scans may show changes in the brain, but diagnosis is made by exclusion; that is, by ruling out everything else that may cause these changes. A more definitive blood test is being discussed in research papers as a possibility in the next few years. On average, a person with Alzheimer’s lives 4-8 years after diagnosis but can live as long as 20 years, depending on factors such as other health conditions and, in part, age at diagnosis.

New Treatment: Aduhelm (Aducanumab)

Aduhelm (aducanumab) was approved by the FDA on June 7, 2021. It is the first new drug to be approved for the treatment of Alzheimer’s in 17 years. Instead of granting the drug a standard approval, which is typically reserved for agents that have demonstrated benefit for people in large phase III trials, the FDA opted to use its accelerated approval pathway, also known as fast-tracking. This path is used for treatments that are reasonably likely, but not certain, to help patients. For reference, fast-tracking has also been utilized by the FDA for cancer drug approvals.

Aduhelm’s fast-tracking approval has resulted in controversy due to the fact that the FDA ignored the advice of its advisory committee and approved the drug based on its ability to lower levels of amyloid plaques (protein clumps that some scientists think cause Alzheimer’s) in the brain. Key here is that there is no direct evidence that plaques themselves cause Alzheimer’s Disease or whether they are a by-product of the Alzheimer’s Disease process. It is also unknown if lowering the quantity of amyloid plaques in the brain will slow the disease progression.

Labeling

Also part of the controversy, Biogen’s clinical trials for Aduhelm were only conducted on early-stage Alzheimer’s patients with mild cognitive impairment. However, Aduhelm’s initial labeling indicated the drug can be used broadly “for the treatment of Alzheimer’s disease,” meaning anyone diagnosed at any stage may be prescribed the drug.

On July 8, 2021, the Food and Drug Administration approved an updated label submitted by Biogen, which specifies that the drug should be initiated in patients with mild cognitive impairment or in the mild dementia stage of disease. Those categories represent the populations in which treatment was studied in clinical trials. The new label specifies that "there are no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than were studied."

Pricing

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Biogen has announced a list price of $56,000 per year for Aduhelm. The Kaiser Family Foundation projects that Medicare could spend $57 billion or more per year on this drug alone, which is more than Medicare Part B spends on all other drugs combined. (In 2019 Medicare spent $37 billion on drugs.) It has been noted that out of pocket costs for Medicare beneficiaries could total as much as $11,500 per year, putting the drug financially out of reach for many seniors and further dividing an already complicated health care system.

The high list price for Aduhelm has been met with criticism. ICER (the Institute for Clinical and Economic Review) reported that the $56,000 per year is “‘not a fair price” for the treatment. In its revised report, ICER said its cost-effectiveness analysis for Aduhelm placed the value of the drug significantly lower – around $3,000 to $8,400 per year of treatment. This reflects an 85-95% discount on the drug’s current list price. ICER feels that the evidence for Aduhelm is insufficient to prove the drug has a net health benefit for patients with mild cognitive impairment due to Alzheimer’s disease, as well as patients with mild Alzheimer’s disease.

Administration

Aduhelm is administered as an infusion over one hour and titrated upwards until it is at the maintenance dose of 10mg/kg every 4 weeks. The length of time the patient will need to be on the medication is unclear at this point. The clinical trials lasted one year. Drug labeling indicates MRIs should be completed at the 7th and 12th infusion to look for microhemorrhages and/or other abnormalities. 

Dosage Forms & Strengths

injectable solution

·       100mg/mL (1.7-mL, 3-mL single-dose vials)

Alzheimer’s Disease

Indicated for treatment of Alzheimer’s Disease

Administered as IV infusion every 4 weeks and at least 21 days apart

Dose and Titration:

Infusions 1-2: 1 mg/kg IV q4Weeks

Infusions 3-4: 3 mg/kg IV q4Weeks

Infusions 5-6: 6 mg/kg IV q4Weeks

Infusion 7 and beyond: 10 mg/kg IV q4Weeks

Side Effects

Like all drugs, Aduhelm comes with side effects for some. The most commonly observed during clinical trials were brain swelling and tiny brain bleeds. Headaches, falls, diarrhea and confusion were also reported. These will require monitoring of the patient by a physician.

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Summary: Cautious Hope

Of course, the hope is for individuals and their families, this would be the first drug that actually slows down the progression of Alzheimer’s disease. That means Alzheimer’s could possibly be considered a chronic disease instead of a fatal disease. It could be a disease that people could live with for many years, in the same way that people are living with cancer, diabetes, and HIV/AIDS.

The fast tracking of Aduhelm has given hope not only to the millions with Alzheimer’s disease and their families, but also to those researchers involved with other neurodegenerative diseases such as ALS, Huntington’s Disease, and Parkinson’s Disease. They see the fast tracking of Aduhelm as a sign of flexibility from the FDA with diseases that have had difficulties finding successful treatments. Other researchers fear that this regulatory precedent puts false hope above solid clinical science and harms patients in the process.

Each health plan will need to determine if it will cover the drug. Likewise, each patient and family along with their physician will need to determine if it is appropriate for them. Our Summit ReSources managed care staff is available to answer any questions or concerns you may have. We will continue to investigate and provide information to our clients as this field of medicine continues to evolve.

Adapted from alz.com.

Adapted from alz.com.