- After nearly 20 years without new treatments, drugmaker Biogen has won accelerated approval for aducanumab, also known by the brand name Aduhelm, a drug that treats Alzheimer’s by attacking the protein plaques associated with this disease.
- Clinical trials confirmed that the drug slows disease progression in its early stages by helping clear plaques associated with the disease.
- But the drug's approval is controversial, as the drug does not clearly show that it improves symptoms.
On Monday, the Food and Drug Administration (FDA) announced accelerated approval for drugmaker Biogen’s Aduhelm, the brand name for aducanumab. It is the first drug to treat a likely cause of Alzheimer's disease, despite controversy around whether clinical evidence proves it works.
While other drugs relieved some symptoms of the condition, Aduhelm has been found in one clinical trial to actually slow the progression of plaques associated with Alzheimer’s in patients with early stages of the disease.
But the drug's approval is also controversial, as it is not clear how beneficial it will be at stopping the clinical symptoms of the disease.
Amyloid plaques associated with Alzheimer’s disease
“In Alzheimer's disease, nerve cell death is due to the deposit of amyloid plaques and neurofibrillary tangles in the brain, and that eventually leads to clinical dysfunction,” Dr. Gayatri Devi, a neurologist at Lenox Hill Hospital in New York who specializes in memory disorders, told Healthline.
According to Devi, author of “The Spectrum of Hope: An Optimistic and New Approach to Alzheimer's Disease and Other Dementias,” a similar process can occur with other forms of dementia.
“For example, in Lewy body disease [a common form of dementia], there are Lewy body deposits,” she said, adding, “There is data that shows that removing or preventing plaques can help in Alzheimer's disease.”
Aduhelm targets underlying disease process
“Alzheimer’s disease is a devastating illness that can have a profound impact on the lives of people diagnosed with the disease, as well as their loved ones,” Dr. Patrizia Cavazzoni, director of the FDA’s Center for Drug Evaluation and Research, said in a statement.
She emphasized that while currently available therapies only treat symptoms of Alzheimer’s, Aduhelm is the first therapy to target and affect the underlying disease process of Alzheimer’s.
“As we have learned from the fight against cancer,” she said, “the accelerated approval pathway can bring therapies to patients faster while spurring more research and innovation.”
According to the FDA, this is the first new treatment approved for Alzheimer’s since 2003.
According to the FDA, Biogen researchers evaluated Aduhelm’s efficacy in two different studies that looked at almost 3,500 patients.
All three were “double-blind, randomized, placebo-controlled, dose-ranging studies” in patients living with Alzheimer’s disease.
Researchers found that patients who received the drug had significant dose- and time-dependent reduction of amyloid beta plaque. But patients in the control arm of the studies, or those not given Aduhelm, had no reduction of this plaque.
Drug’s approval is controversial
The findings of the studies didn't clearly show that people were likely to have fewer symptoms of Alzheimer's disease if they were taking the drug. In one of the studies, researchers found a small benefit for people taking the drug. In the other study, however, no benefit was seen.
The FDA has asked that Biogen now start another trial to verify that the drug actually works. If that trial fails, the FDA could revoke approval.
According to the FDA, not all experts agreed that Aduhelm merited accelerated approval.
“The data included in the applicant’s submission were highly complex and left residual uncertainties regarding clinical benefit,” said the FDA in a statement. “There has been considerable public debate on whether Aduhelm should be approved. As is often the case when it comes to interpreting scientific data, the expert community has offered differing perspectives.”
The FDA confirmed that it examined the clinical trial findings with a “fine-tooth comb,” solicited input from the Peripheral and Central Nervous System Drugs Advisory Committee, reviewed all relevant data, and “listened to the perspectives of the patient community” before making their decision.
Taken by injection and may cause serious side effects
According to the new treatment’s label, Aduhelm is administered by injection as an intravenous infusion for about 1 hour every 4 weeks, and patients might experience side effects that include:
- cerebral edema, or swelling of the brain
- bleeding from the brain
- amyloid-related imaging abnormalities (ARIA)
- angioedema, or swelling beneath the skin
- urticaria, a reaction similar to hives
According to the drugmaker, some patients in Aduhelm clinical trials also experienced adverse effects like falling, diarrhea, and disorientation.
Due to the potential for brain swelling and brain bleeding, those taking the drug will need to undergo MRIs to ensure they're not having serious side effects.
Aduhelm comes with a hefty price tag
However, he also said the biotech company has vowed not to increase the price of the medication for the next 4 years.
Vounatsos explained the price of the drug reflects “two decades of no innovation,” and will allow Biogen to invest further in their pipeline of medicines for other diseases, he said during an interview with CNBC’s “Power Lunch,” reported CNBC.
Biogen will conduct post-approval clinical trial
Even with accelerated approval, Aduhelm will continue to be studied.
According to the FDA, this type of approval can be based on a drug’s effect on a “surrogate endpoint that is reasonably likely to predict a clinical benefit to patients,” but requires a post-approval trial to “verify that the drug provides the expected clinical benefit.”
These are called phase 4 confirmatory trials and are intended to verify a treatment has clinical benefit. Failing to show efficacy in this trial could result in the FDA rescinding their decision.
“It's conceivable that negative findings could lead to retraction of approval,” said Devi. “In general, phase 4 trials allow for more data gathering,”
Aduhelm is only part of treatment, says Alzheimer’s Association
“This therapy will be of great interest to many, but it is not the only important element of Alzheimer’s treatment and care,” said Joanne Pike, DrPH, and chief strategy officer at the Alzheimer's Association, in an emailed statement.
“The Alzheimer’s Association has made it a priority to partner with healthcare systems, physicians, and the Centers for Medicare and Medicaid Services to ensure early and accurate diagnosis, and access to treatment, care management, and care planning,” she continued.
Pike added that the association would do everything in its power to ensure access to the drug and FDA-required diagnostic testing for all who will benefit, and that eliminating barriers to access “is our highest priority.”
The bottom line
After nearly 20 years without new treatments, drugmaker Biogen has won accelerated approval for Aduhelm, the brand name for aducanumab, a drug that treats Alzheimer’s by attacking the protein plaques associated with this disease.
According to Biogen, multiple separate clinical trials confirmed that the drug slows disease progression in its early stages. But its approval is controversial, as the drug does not clearly show that it improves symptoms.
Experts say the drug is only a facet of Alzheimer’s treatment, and early diagnosis, access to treatment, care management, and care planning, are critical components in caring for people with the disease.