FDA Caught in Political Crossfire

With the national election taking place at a time of desperate hope for new vaccines and therapies to combat the lethal coronovirus, FDA officials are struggling to maintain the credibility and independence of its drug regulatory process amidst accusations of intentionally delaying clinical testing for political reasons. In response to calls from Democrats for better strategies to prevent and treat COVID-19, President Trump ramped up charges that FDA staff look to limit access to needed therapies.

On August 22, Trump blasted FDA for blocking efforts to test and approve a COVID vaccine before election day. The entire research community acknowledges that sponsors and public health authorities are moving at record speed to test potential vaccines, enabling several sponsors to launch Phase III trials for promising products. While some early data may appear this fall, its unlikely that the public will see clear results on efficacy and safety from these very large studies in just two months. And with many of the early studies being conducted overseas, FDA would face challenges in approving a vaccine based on foreign clinical trial data.

That prompted a Trump “tweet” on August 22, 2020 that the “deep state” at FDA was “making it very difficult for drug companies to get people in order to test the vaccines and therapeutics.” The aim of agency staffers, he said, was to “delay the answer until after November 3”.

To be able to claim some victory in tackling the pandemic on the eve of the Republican convention, the President trumpeted progress in treating patients with COVID convalescent plasma (CCP) from recovered individuals. At a Sunday evening press conference on August 23, 2020, FDA Commissioner Stephen Hahn joined President Trump and Health and Human Services (HHS) secretary Alex Azar to announce it had issued an emergency use authorization (EUA) for convalescent plasma that would make it easier to provide this treatment to COVID-19 patients. Trump heralded the move as “truly historic” and that FDA “really stepped up, especially over the last few days” to take this action.

At the press briefing, Hahn said the agency was encouraged by “promising data” from recent studies, and that analysis indicated that potential benefits of administering CCP outweigh risks. The evidence came from early reports on two small trials and a large expanded access protocol sponsored by the Mayo Clinic, which has provided plasma to more than 70,000 patients. A Clinical Memorandum from the Office of Blood Research and Review (OBRR) in the Center for Biologics Evaluation and Research (CBER), summarizes the study data showing that CCP “may be effective,” but that patients will benefit more if CCP is administered early in the course of disease and has higher antibody levels.

Such “optimal patients” treated with plasma at the highest antibody titers showed “significant clinical benefit” in survival, Hahn said. But he sidestepped the White House claim that CCP was a “powerful therapy” that reduced mortality by 35%, noting that data so far did not come from randomized trials.

The EUA approval followed considerable analysis and debate within FDA and other federal health agencies over the scope and timing of an authorization. Last week, FDA indicated it would hold off on an EUA due to objections from leaders of the National Institutes of Health (NIH) and the National Institute of Allergy and Infectious Diseases (NIAID) that evidence of efficacy was too limited and that an EUA would make it harder to obtain clear risk-benefit information on how best to use this treatment. While some 150 clinical trials are testing plasma treatment, few are sufficiently randomized and controlled to produce clear data. Additional information on testing and developing convalescent plasma treatments is provided by CBER.

Vetting vaccines

While some public health authorities support the EUA as not likely to harm patients and may be beneficial, recent events raise fears that the administration will continue to press for approval of a COVID vaccine before all the evidence is in. Hahn and his deputies have maintained that FDA will “rigorously” evaluate all the evidence on vaccine safety and efficacy and will refer to the agency’s earlier guidance recommending that vaccines be at least 50% more effective than placebo in preventing COVID-19 infection. And to ensure a transparent, unbiased, science-based evaluation, the agency will discuss clinical trial data on vaccine candidates with its advisory committee on vaccines, starting with a meeting tentatively scheduled for October 22, 2020.

All eyes will be on CBER Director Peter Marks, who recently stated that he would resign if policy makers seek to approve a vaccine before data shows that it is safe and effective. According to press reports, Marks emphasized that so far FDA has not faced such political pressure, but that efforts to put something unsafe or ineffective through the approval process was his “red line.” Marks also said he would respond similarly if parties sought political gain by delaying approval of a vaccine shown to work safely.

Any perception that FDA approval decisions on vaccines and therapeutics reflect political pressures—as opposed to scientific evidence—stands to further undermine public confidence in the benefits and safety of any COVID vaccine. The already accelerated pace of product development has fueled anti-vaccine campaigns, and caveats raised by President Trump may further encourage vaccine hesitancy. Biopharma companies, research leaders and the medical community recognize the importance of an independent and credible FDA that maintains worldwide respect for its science-based regulatory decisions. Political moves that challenge the agency’s authority will only hinder efforts to address today’s world health crisis and the economic turmoil and public health catastrophe affecting billions.