FDA's recent approval of a controversial drug -- aducanumab (Aduhelm) -- to treat people living with Alzheimer's disease shows just how broken the agency is, and reminds us that we all have to pay for it.
A series of events that has unfolded since January tells the story.
In late April, the FDA's Oncologic Drugs Advisory Committee reviewed six accelerated approvals -- a provisional pathway -- involving a group of cancer immunotherapies where clinical trials had failed to confirm that the drugs extended survival or improved quality of life. Yet, in four of the six cases, the advisory committee voted to keep the accelerated approvals intact. The lesson was painfully clear: once the toothpaste is out of the tube it is hard to get it back in. Once doctors get used to using a therapy, pulling a drug from the market or in this case, revoking indications, is hard -- even after the drugs fail to confirm benefit.
On June 7, the FDA approved aducanumab for the treatment of Alzheimer's disease. The drug received accelerated approval because it showed it could reduce the rate of amyloid plaque on scans. What remains uncertain is whether this reduction in plaque means Alzheimer's patients live longer or better lives -- and notably, the totality of the clinical trial data do not show that. Moreover, the drug has various side effects and a whopping price tag: $56,000 a year.
In response to the FDA's approval, three members of the Peripheral and Central Nervous System Drugs Advisory Committee who opposed approval of the drug, quit the panel in protest. Aaron Kesselheim, MD, JD, MPH, a Harvard professor called the drug "problematic," and argued that there was it would help patients. Writing in The Atlantic, Nicholas Bagley, JD, and Rachel Sacks, JD, MPH, estimate that if the drug is prescribed to just one-third of eligible patients, it would a year -- a massive figure that dwarfs any other medication.
What Is FDA Thinking?
In the last 3 months we have seen that the FDA does not have the ability to revoke accelerated approvals, even when the drugs and their sponsors fail to meet the promises made. And to wash that down, the FDA has now approved another uncertain drug for people suffering from Alzheimer's, against the wishes of a different advisory panel. With Alzheimer's disease affecting 6 million Americans, the financial and human implications of the approval are staggering.
FDA Has Pitched Their Tent on the Side of the Mountain
Many observers don't fully appreciate how the FDA has taken a position that is indefensible. The agency does not guarantee that drugs that come to the U.S. market actually help Americans live longer or better lives (beyond what could be achieved without these drugs). At the same time, the FDA insists on interfering in the market and sets arbitrary standards for approval. The combined effect is the worst of all possible worlds: we don't know if drugs work, and the companies can charge massive prices for them!
Let's consider, two views of what the FDA could be.
One vision of the FDA -- held by progressive reformers -- is that the purpose of the agency is to shield desperate, sick, and vulnerable patients from making choices that may not be in their best interest. That is why we demand drugs be safe and effective, and not let any charlatan sell you any snake oil. The FDA exists to protect the American public from taking toxic drugs that don't work. By that metric, our system has failed. The FDA often makes products available with no robust proof they are effective -- such as in the case of aducanumab -- and remains reluctant to withdraw the products or specific indications even when trials fail to confirm the benefit of living longer or better lives.
The other vision for the FDA is to abolish it entirely. Some libertarian policymakers argue that without the FDA, the market would work itself out. Without the agency, the barrier to sell a drug would be dramatically lowered. Small companies that cannot afford to jump through the FDA's regulatory hoops might be able to bring small-batch products to market. Prices would tumble as drugs would flood the market and compete based on price and patient experience. In this vision, word of mouth would help clarify which drugs were effective, and some payers might conduct good randomized controlled trials to decide whether to fund products. I am not in this camp -- I see dangers with this approach -- but even I must concede, prices would likely fall.
Yet, instead of either of these visions, we have an agency that lives in between the two. The FDA poses a series of hurdles to get a drug to market, but none of those hurdles are an assurance a drug works or has net benefit to people. Then the agency stamps drugs with their imprimatur. Ironically, this system is ideal for medium and large pharmaceutical firms. Small firms are kept off the market, and larger firms specialize in jumping through the hoops. Once approved, costs can be astronomical, and the FDA seal of approval justifies the high price. Along the way, no one seems to ask whether patients are better off.
From this vantage, the FDA looks like an agency whose goal is to preserve pharmaceutical profits. Coincidentally, among medical reviewers at the agency, the after working at the FDA is either as a consultant for or employee of a biopharmaceutical company.
Just this week, yet another former FDA Commissioner, Stephen Hahn, MD, a venture capital firm in healthcare.
What is the American public to think? We have an agency that is happy to approve $100-billion-a-year drugs to a desperate and vulnerable population without knowing that patients are better off. Society pays for those costs -- often through Medicare -- but that same society won't pay for a caregiver who might actually ease the burden on families who have a loved one with Alzheimer's. If drugs approved by accelerated approval later don't work, experts are happy to continue to keep them on the market, citing anecdotal impressions of their utility. The bar for approval is ridiculously low, but not absent altogether -- a fact that facilitates high drug prices. Finally, the people who work at the FDA later go to work predominately for the companies that profit from the FDA's lax standards. The revolving door spins so fast it might hit you in the rear.
Our system is grievously and horribly broken. I have been following it closely and my worry is that I see no signal it is getting better any time soon.
is a hematologist-oncologist and associate professor of medicine at the University of California San Francisco, and author of .