Gregg Gonsalves feels guilty. Now a professor at Yale’s School of Public Health, Dr. Gonsalves remembers standing with other AIDS activists outside the Food and Drug Administration headquarters in the 1980s, accusing the agency of murder for not approving medications that might save lives but hadn’t been proven effective in clinical trials yet. “People were dying. We didn’t know what to do,” Gonsalves told me.
The activists demanded an expedited approval process for medications that showed potential with improving immune system markers like CD4 cell levels, while studies on whether the drugs actually prolonged lives were still being conducted. Rapid approval, even before a drug was shown to help, could mean the difference between life and death, they argued.
In 1992, the FDA established precisely this kind of rapid approval process. Now the FDA has used it to approve a controversial drug for Alzheimer’s disease, even as the agency hasn’t fully approved Covid vaccines with far greater evidence of efficacy. Aduhelm, a drug produced by a company called Biogen, reduces a type of brain plaque that is associated with Alzheimer’s—but it’s not yet clear if the medication can help control or halt the disease itself. Thanks to the FDA’s accelerated approval in June, patients can start using the drug to see if it helps while trials continue. But at a price tag of $56,000 every year, with thousands of dollars in other potential medical bills for monitoring side effects like brain swelling, families desperate for a wonder drug could also be bankrupting themselves for nothing.
Six months into Biden’s presidency, the FDA is in turmoil; the administration still hasn’t even named a commissioner to lead the agency. The hasty Aduhelm approval shocked observers, in part because the agency has yet to offer full approval to Covid-19 vaccines despite millions of successful and safe vaccinations. With Pfizer expected to file within weeks for another emergency use authorization for a third Covid booster shot, and the highly contagious delta variant spreading, fully approving the Covid vaccines could offer the country a much-needed vaccination boost. “The FDA is close to hitting rock bottom,” Gonsalves said.
The lack of a nominated commissioner, during one of the most turbulent times in recent history, could have long-term implications for the agency. Without a confirmed commissioner, it’s difficult for the agency to form and execute policy. “We have leaders for a reason. And the FDA right now has no leader,” one longtime representative for pharmaceutical companies and other FDA-regulated industries, who asked not to be identified by name, told me. “I don’t think the FDA is going to get out of this mess until they get a confirmed commissioner.”
Yet progress on that front seems to be stalled. After floating a short list of potential commissioners earlier in the year—the current acting leader Janet Woodcock and Obama FDA official Joshua Sharfstein—the Biden administration then suggested a few more names in April. When I contacted an FDA spokesperson for comment on the commissioner nomination process, they referred me to the White House, which did not respond to press inquiries. In March, six former commissioners signed a letter asking Biden to make the choice soon. Lawmakers have also called for quickly filling the position—but they remain divided along partisan lines about how many ties a commissioner should have to the pharmaceutical industry.
Last year, the FDA made several major missteps in addressing the pandemic, authorizing antibody tests as well as treatments like hydroxychloroquine and convalescent plasma on the thinnest of evidence. Experts were terrified that, in addition to the FDA’s own decisions being rushed, President Trump would overrule the agency and force the authorization of Covid vaccines before Election Day. But then-Commissioner Dr. Stephen Hahn stood firm and directed the agency to wait until the trials were complete and the data had been analyzed. Gonsalves called it “a high point of last year” and proof that “not everything is falling apart at the FDA.”
“The FDA played it straight on vaccines, and we should be grateful. But it doesn’t let you ignore the larger trends that are at work,” Gonsalves added. And last year’s political battles, which thrust the FDA in the public spotlight, may have done lasting damage to public trust and perception about regulations.
“I have never seen anything like this. The political interference, or the appearance of attempted political interference, was frankly shocking,” the longtime industry representative said. “I think that Trump did tremendous damage to the agency by attempting to coerce it, and complaining about it, and insulting the agency, ridiculing the agency, reviling it, accusing it of being political. And that stuff tends to stick.”
But now that there’s ample evidence the vaccines are both safe and effective, the agency’s failure to offer full approval for the Pfizer-BioNTech, Moderna, and other vaccines also puzzles experts. “Why they haven’t issued the approval, I simply don’t understand it,” the observer said. “I can’t imagine anything that’s a higher priority.”
“The FDA recognizes that vaccines are key to ending the Covid-19 pandemic and is working as quickly as possible to review applications for full approval,” an FDA spokesperson told me via email. The FDA is now sorting through the extensive data collected on the vaccines—and Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, has hinted that some of that data was delayed, writing recently that the approval of the vaccines “depends on the submission of complete applications by the companies.”
Dr. Eric Topol, director and founder of the Scripps Research Translational Institute, has argued for the vaccines’ approval, in large part to improve vaccination rates in the United States. “I do think that’s the biggest thing we can do right now to get the United States on track,” he told me. Once the vaccines are approved, employers and organizations—from hospitals to schools—can require either vaccination or masking with frequent testing, he said. “The day that happens, with full FDA licensure—which should’ve happened by now—we will see a big jolt. Tens of millions of people who get vaccinated because they realize there’s no way out, because they don’t really want to wear a mask and get a swab up their nose frequently.” As the highly contagious delta variant spreads, the country desperately needs the vaccination jump that full approval would offer.
“There’s just no excuse anymore, just no excuse,” Topol said. (He has said he was approached as a potential candidate for the commissioner job, but he declined.) “And here they approve the Alzheimer’s drug, which had no data yet, and they approved that based on 3,000 people—and here we have hundreds of millions of people where the proof is there of the safety and effectiveness” of vaccines, he said. “I’m extremely frustrated. Every day I get more frustrated, because that is the singular thing that could change this thing around.”
Last Thursday, in the face of criticism, the FDA narrowed Aduhelm’s recommendations for use to mild cases of Alzheimer’s—which more closely aligns with the trials Biogen conducted. But, the FDA spokesperson told me, “some patients may benefit from ongoing treatment even if they progress from mild cognitive impairment or mild dementia to later stages of the disease during treatment.”
On Friday, the acting head of the agency, Janet Woodcock, called for an independent investigation into how the drug was approved, after reports of FDA officials working closely with Biogen to gain approval. The agency’s own statisticians said there is little data so far to show the drug works, and the advisory committee of outside experts recommended against approval without more data; when the agency approved it anyway, several advisers quit in protest.
In the long term, good regulations help the pharmaceutical industry enormously. Undermining regulations, or pushing out drugs that don’t actually work, could undermine the credibility of the entire industry. And approving drugs in the hope that they might work could do more harm than good.
“Patients need more than hope,” Gonsalves told me. “Patients need drugs that keep them alive.” What troubles him about the FDA’s seemingly arbitrary approval pattern in the past year is that it frequently seems to serve pharmaceutical companies rather than patients. AIDS activists, he recalled, quickly abandoned the push for FDA authorization in favor of demanding more funding and better research from the National Institutes of Health. But drug companies had already latched onto the idea of a fast track: “We got hijacked by the pharmaceutical industry and its allies to use our early, most naïve moment as their own rallying cry today in the most cynical way,” he said.
“By the early ’90s, we were very, very worried about what we’d just done.… We realized it’s not the case that any drug is better than no drug at all, or that a new drug is better than an old drug,” Gonsalves added. “True blockbusters and therapeutic advances are rare, and they take a long time.”
The irony is that Covid vaccines really do seem to be one such blockbuster. (They, too, took time: almost a decade of research since the first SARS outbreak, as well as years of work on platform vaccines.) Why the FDA has withheld approval from them while offering it to Aduhelm is a question people will be puzzling over for a long time to come. At this critical moment in FDA history, the choices the agency makes—and the Biden administration, in nominating a leader—could reverberate for decades.