Editor's Note (January 29, 2021): The FDA has requested additional information, including clinical trial data and analysis, on Biogen’s Alzheimer’s drug aducanumab. A decision on approval now is expected by June 2021.
Biogen’s aducanumab — a therapy that aims to slow Alzheimer’s progression — is back in the news. Last week, an advisory panel of medical experts recommended against approval, citing lack of sufficient evidence that the drug slows cognitive decline. (This contrasted with positive recommendations from an internal FDA panel earlier in the week.) The advisory panel’s recommendations can influence the approval decision, but the FDA has the final say. Their formal decision is expected on or before March 7, 2021.
What is aducanumab?
The drug is a monthly infusion (given by IV) that aims to remove amyloid beta plaques, a hallmark of Alzheimer’s, which are thought to lead to brain cell loss and memory and thinking changes.
Why is this drug so closely watched?
Millions of people worldwide live with Alzheimer’s and other dementias. Currently available drugs, such as Aricept (donepezil) or Exelon (rivastigmine), treat symptoms but do not impact underlying disease.
What’s the research on aducanumab?
The drug was studied in two, identical Phase III trials — EMERGE and ENGAGE — which evaluated different doses in more than 3,200 people with early Alzheimer’s. Both trials looked at cognitive changes, using clinical scales, as well as a number of biomarkers, such as the amount of amyloid in the brain.
In March 2019, a futility analysis (which looks at whether a trial will meet its goals) concluded that the drug did not slow progression and both trials were stopped. A few months later, Biogen announced that, on further analysis of additional data, the drug did have an effect. In summary, says Kenneth Marek, MD, president and senior scientist at the Institute for Neurodegenerative Disorders and scientific advisor to The Michael J. Fox Foundation, “The additional analysis showed that, at the highest dose of aducanumab, there was a significant clinical effect, of small magnitude, which was supported by very robust biomarker effects — dramatic changes in brain amyloid.” Because of conflicting results from the two Phase III trials (ultimately one was positive and the other negative) and the way in which the additional analysis was conducted, some have doubts about the proposed benefits.
What could this mean for Parkinson’s?
Aducanumab uses antibodies to target harmful amyloid-beta protein in the brain. Similar therapies — antibodies targeting alpha-synuclein, the hallmark of Parkinson’s — are now in clinical testing to slow Parkinson’s progression. Understanding if and to what degree aducanumab works, as well as its side effects and, if approved, how best to use it, will benefit PD drugs in development.
What happens now?
The FDA reviews all data in addition to recommendations from the two advisory panels. A decision on approval is expected by March 2021.