Election undermining activities

Beyond the curve: Dr. Peter Lurie's COVID-19 blog

Many of us in public health have toiled for years in the alphabet soup of 3-letter acronyms: FDA, CDC, DPT, and so on. But we never dreamed that some would become household names. Who would have thought dinner table conversations would have offhandedly referred to PPE? Or a more recent arrival: EUAs.

Emergency Use Authorizations are a tool provided by Congress that allows FDA to temporarily authorize (not approve) a medical product for certain serious or life-threatening diseases or conditions during public health emergencies. The authority has been appropriately wielded in the current pandemic to usher to market diagnostic tests, ventilators, and the proven effective drug remdesivir.

But the mechanism has been shrouded in controversy, ever since pressure from the White House contributed to the granting of an EUA for hydroxychloroquine, a decision the agency was forced to retract when clinical trial data proved the drug ineffective. And sometimes FDA has flailed in the opposite direction: it initially permitted antibody tests on the market without EUAs, but was then forced to reverse course and require applications for EUAs when many tests proved unreliable. Predictably, a number of companies didn’t even bother applying.

But recently the hitherto obscure bureaucratic tool has attained a newfound prominence. Back in August, on the eve of the Republican convention, the President used a hastily convened press conference to announce that convalescent plasma had received an EUA. The FDA, which had dutifully conferred the EUA under White House pressure, was in turn showered with a deluge of criticism for hyping the product in the absence of the kind of data that would have justified an EUA in prior epidemics.

Since then, convalescent plasma has been relegated to relative obscurity. But the wheels of science have continued to grind. Several randomized, controlled trials have now been completed and none shows convincing evidence of a mortality reduction or clinical benefit. Looks like it’s time for FDA to reconsider the convalescent plasma EUA.

Meanwhile, the President’s notoriously abbreviated attention span was shifting elsewhere. This week, his hopes for a vaccine before election day appeared to recede still further. FDA had prepared a guidance recommending a median of at least two months of follow-up following vaccination in the ongoing Phase 3 clinical trials, likely placing even the earliest end date for all or most of the trials beyond Election Day. The agency submitted its guidance to the White House where it came to the attention of that veteran clinical trialist, Trump Chief of Staff Mark Meadows, who apparently consigned it to bureaucratic purgatory. Trump himself, as ever availing himself of authorities that are not his, announced that he “may or may not approve it.”

But FDA outplayed the White House by releasing a version of the guidance as an Appendix to briefing materials for the upcoming meeting of FDA’s Vaccines and Related Biological Products Advisory Committee on October 22. Miraculously, the White House released the guidance hours later. The guidance also explained that before granting an EUA for any particular vaccine, it would convene an Advisory Committee meeting, separate from the one on October 22 (at which I’ll be presenting). Having put these Advisory Committee meetings together while I was at FDA, I can attest that process will certainly take weeks.

Meanwhile, he who had been so belligerent and confrontational on the debate stage on the Tuesday had been laid out by a submicroscopic organism by the Thursday. But help was on the way, at least in the President’s telling, in the form of monoclonal antibodies from the pharmaceutical company Regeneron.

The drug was part of a cocktail of drugs the President received, including remdesivir and dexamethasone, products actually proved to benefit patients with serious COVID-19 infections in randomized, controlled trials, as well as a potpourri of unproven nostrums including zinc, vitamin D, and famotidine (a drug supported by Operation Warp Speed under questionable circumstances). But when he claimed to feel better, the President was certain it was the Regeneron product, proclaiming it to be a “cure” even though he’s not out of the woods yet.

But the President went further. If it works for me, he said, employing a form of epidemiological narcissism, it should be available to everyone for free. Never mind that the company only has enough of its product on hand to treat 50,000 people – about as many as the current number of U.S. infections per day.

Turns out Trump had spent time on the links with Regeneron CEO Leonard Schleifer, who was a member of the Trump National Golf Club Westchester. Trump held stock in the company at one time and Regeneron is funded to the tune of $450 million by Operation Warp Speed, the government’s ill-named vaccine and therapeutics initiative.

Which brings me back to the EUA. Both Regeneron and Eli Lilly, which also makes a monoclonal antibody drug, have applied for EUAs, though both have so far opted for publicizing their clinical results by press release rather than in a peer-reviewed journal, where clinical results could be more rigorously evaluated. I’ve outlined my concerns about the data available for the Regeneron product before, and won’t reiterate them here. But Trump and Meadows have called FDA Commissioner Stephen Hahn, urging him to accelerate the review of the products, a degree of involvement from the White House in drug regulatory decision-making unprecedented in my experience.

At least monoclonal antibodies have a theoretical basis for efficacy that exceeds those for hydroxychloroquine or, need I say it, bleach or ultraviolet light, products that previously caught the President’s imagination. But, at the end of the day, we need to see full reports of completed randomized, controlled trials before an EUA can be issued. What we don’t need yet again is the politically motivated granting of an EUA, potentially discouraging enrollment in the ongoing clinical trials that could answer the questions around product safety and effectiveness definitively.