Ordinarily, the approval of a new drug for a dreaded disease affecting millions of Americans would be a cause for celebration. But aducanumab, which the Food and Drug Administration approved last week to treat Alzheimer’s disease, is no ordinary drug. It encapsulates everything that ails the regulation of the pharmaceutical industry and is a grim reminder of the soul-searching about the FDA’s integrity that’s desperately needed.
What’s so bad about aducanumab? By law, the FDA is supposed to approve only drugs that prove to be safe and effective. But no robust evidence exists for this drug, as an FDA committee of independent experts found almost unanimously.
Yet the FDA ignored those experts and approved the drug anyway, based on its ability to reduce amyloid plaque in the brain — even though multiple clinical trials have yet to show any association between plaque and Alzheimer’s disease progression. Three members of the committee have since resigned in protest.
The FDA will require the drug’s manufacturer, Biogen, to conduct additional clinical trials to generate more evidence of aducanumab’s effects, but won’t demand results before 2030, meaning patients could take the drug for nine years without really knowing whether it works.
Meanwhile, the drug might be dangerous — even deadly. Across the two largest clinical trials, approximately 40 percent of trial participants receiving a high dose of aducanumab developed brain swelling or bleeding.
It’s also expensive. Given its high price tag and huge number of patients who might use it, U.S. health care spending could swell by $112 billion annually just from this one drug.
This isn’t the first time FDA allowed its standards to slip. In 2016, it approved eteplirsen for Duchenne muscular dystrophy, despite no evidence of therapeutic benefit. The drug’s manufacturer charges as much as $1 million per year, though five years later, it has yet to generate convincing evidence of efficacy. FDA has also approved other drugs on skimpy or questionable evidence, such as flibanserin, a drug for female sexual dysfunction, and a host of cancer drugs.
How did the FDA get to this point? Congress is partly to blame. For years, the Prescription Drug User Fee Act (PDUFA) has tethered a growing portion of the FDA’s operating budget to “user fees” that the FDA charges its “customers” in the pharmaceutical industry. PDUFA created incentives for the FDA to view its role as serving industry, as opposed to the public. As part of the law, the agency is regularly evaluated by the number of approvals it issues each year, how quickly it makes its decisions and whether it meets industry-set deadlines.
Additionally, politicians on both sides of the aisle have supported legislation such as the 21st Century Cures Act — signed into law by President Barack Obama and championed by then-Vice President Joe Biden as well as the pharmaceutical industry — that has further corroded the FDA’s ability to enforce rigorous safety and efficacy standards in new drug approvals. The intent of the 21st Century Cures Act and other federal legislation might be to get new cures to patients faster, but its actual effect is to weaken the agency’s power to protect the public from unsafe and ineffective drugs.
There’s also the question of whether the FDA has fallen into regulatory capture. The Center for Drug Evaluation and Research, the FDA division that approved aducanumab, is run by Patrizia Cavazzoni, a veteran of the pharmaceutical industry, with long stints at Pfizer and Eli Lilly. Acting FDA commissioner Janet Woodcock is a longtime public servant, but she, too, has been widely accused of being too friendly with the pharmaceutical industry, most notably when she openly worried about Sarepta’s stock price while presiding over the approval of its drug eteplirsen.
Furthermore, the revolving door through which FDA leaders end up in industry spins at an alarming rate. Shortly after leaving his post as commissioner, Scott Gottlieb joined the board of Pfizer. And just recently, his successor, Stephen Hahn, joined Flagship Pioneering, a financial backer of Moderna.
The many good people at the agency fighting to uphold scientific standards need support. The best way to do this is to revive and restore trust in the FDA.
Here are four ways this can be accomplished: First, Congress needs to appropriate sufficient funding to ensure competitive salaries for the FDA’s workforce, adequate staffing and greater resources for non-premarket evaluation activities. Second, leadership across all levels must commit to maintaining its independence in regulating treatments, including by making any meetings between companies and the agency public. Third, FDA leadership must champion strong evidentiary standards for all approvals, expedited or standard, relying on the analyses of its own scientists and the recommendations of its expert advisory committees to make decisions. Finally, the FDA must commit to publishing full documentation of its internal discussions about approvals in its so-called approval packages, as is required by law.
No one is served by approving drugs like aducanumab. Its approval erodes confidence in what we put in our bodies, what doctors prescribe, what we pay for and what companies produce and sell. If we want effective treatments for Alzheimer’s disease and other conditions, we have to create a system that incentivizes innovation and true therapeutic advances, not a race to the bottom, where drugs with no proven benefit are allowed on the market.
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