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The most important news in healthcare: Friday, June 4th
Today, we’re covering a roller coaster that the biotech world has been on for the last two years — the aducanumab story. The controversial Alzheimer’s drug will be either approved or rejected by the FDA come Monday. Read on to learn why many people are calling this the FDA’s most important decision in years.
Today’s Pulse is 800 words, or a 7 minute read.
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PharmaFDA Decision over Controversial Alzheimer’s Drug Approval
The pulse:
It’s been more than 18 years since the FDA approved a new drug for Alzheimer’s dementia. This coming Monday, Biogen is hoping its experimental drug aducanumab can break that cold streak.
What is aducanumab?
Aducanumab is an antibody that targets plaques called β-amyloid. If you believe in the amyloid hypothesis, you believe that it’s the aggregation of these β-amyloid plaques that drives the pathogenesis of Alzheimer’s. This theory in itself is controversial, as some scientists and physicians have spurned the amyloid hypothesis in recent years. You can read more about the amyloid hypothesis in this Past Pulse.
Aducanumab was developed by Biogen and at first, viewed with giddy optimism by clinicians and patients’ families alike. After early studies, it was highlighted on the cover of Nature back in September 2016 and an accompanying editorial said it would be “a game changer in the fight against Alzheimer’s disease”.
So why is it so controversial?
After the Nature cover, Biogen went on to design two clinical trials for aducanumab to work towards FDA approval. However, by early 2019, things were looking grim and Biogen announced they had decided to run a “futility analysis” on interim data of the two trials (meaning data collected before the trial had been completed). This is done when a company thinks there is likely very little chance that the clinical trial succeeds. A futility analysis essentially weighs costs of continuing the trial against the likelihood that the trial shows promising results. On March 21, 2019 Biogen announced that their futility analysis was in favor of shutting down the two trials.
While this was assumed to be the end of aducanumab, seven months later, Biogen unexpectedly announced that it had changed its mind. After a full data analysis, one of the two trials seemed to show that high doses of aducanumab led to cognitive benefit in Alzheimer’s patients as compared to placebo. Based on these new analyses, Biogen decided to apply for FDA approval.
Despite Biogen’s confidence, an FDA advisory committee that met last November voted 11-0 against approval. At that time, the FDA’s statistical reviewer said “there was no compelling substantial evidence of treatment effect or disease slowing and that another study is needed." Many others have echoed the sentiment that another trial is needed, including Dr. David Knopman, a Mayo Clinic neurologist who oversaw the aducanumab trials.
Source: FiercePharma
What is the case for approval?
Many families of Alzheimer’s patients are begging for approval (including many of those who were included in the clinical trial) saying even a slim possibility of benefit would be worthwhile. The Alzheimer’s Association has launched an initiative called More Time to encourage FDA approval. The association’s chief science officer Dr. Maria Carrillo said “it is a moment of hope because it is the first drug that has made it [to the point of being considered by the FDA] in 17 years.”
The FDA’s reputation
Given the controversy that has plagued this drug, the entire pharma sector is watching this story closely. An approval based on such questionable data could definitely damage the FDA’s credibility and set a precedent for approval despite shoddy trial design. The FDA may instead delay the decision or request Biogen to perform another clinical trial.
Most importantly, the consequences for patients and families of an unproven drug could be devastating. About 2 million Americans could be prescribed aducanumab. Let’s put cost aside (though at a price of $20,000 to $50,000 per year, that’s easier said than done). There’s little evidence of compelling benefit; however, there are very real risks — aducanumab can cause microscopic hemorrhages in the brain that lead to brain bleeds and swelling. Patients and families may take on these real risks while hoping for a hypothetical benefit.
Additionally, Alzheimer’s patients may opt for the approved aducanumab instead of enrolling in other clinical trials for investigational drugs, which could actually slow progress in this space.
Bottom line it for me:
Given the nightmare that has surrounded aducanumab’s clinical trials, it’s difficult to imagine the FDA will approve it come Monday. It may instead call for Biogen to run another clinical trial — what most experts have been saying since 2019.