The FDA claims the treatments are ineffective against Omicron while DeSantis officials say the agency has insufficient evidence to rule them out.
Over the summer, while the White House was shouting “get vaccinated” from the rooftops, Florida governor Ron DeSantis was trailblazing monoclonal antibodies as a supplemental treatment for Covid-19. DeSantis didn’t present the treatments as an alternative to inoculation; he distributed them as part of his strategy to stock his state’s medicine cabinet with weapons to fight the virus. The uptake was huge, as was the performance in reducing severity and duration of illness.
The governor’s pandemic management has been characterized by allowing Floridians to make their own choices about masking, vaccination, and treatments, while the Biden administration has preferred aggressive intervention, producing tension between Florida and the feds. The mistrust deepened when DeSantis officials started accusing the administration of subverting and limiting the circulation of antibody treatments so the population would have nowhere to turn but the vaccine. In December, Florida surgeon general Joseph Ladapo alleged that the federal government was “actively preventing the effective distribution of monoclonal antibody treatments.”
The U.S. Department of Health and Human Services had reportedly reduced the allocation of certain monoclonal antibodies to Florida due to mounting evidence that they didn’t target the Omicron variant sweeping the nation. Regardless, Ladapo wrote to HHS secretary Xavier Becerra that “the federal agencies under your control should not limit our state’s access to any available treatments for Covid-19.”
On Monday, the plot thickened when the FDA suspended emergency-use authorization (EUA) for two monoclonal antibodies, declaring them ineffective, a move that DeSantis claims has left Florida in a very vulnerable position. But while the governor argues for offering maximal resources, including even unproven therapeutics, the FDA claims it has a scientific and ethical obligation to protect consumers from useless medicine.
Omicron, a highly infectious and diverse strain, has many mutations that make it more likely to evade older therapeutics, posing a challenge for scientists. The FDA claimed it revoked approval for the pair of drugs based on scientific studies showing that bamlanivimab/etesevimab, produced by Lilly, and REGEN-COV, produced by Regeneron, do not combat the new variant.
The FDA did not meet its burden of proof to justify taking these therapeutics off the market for Floridians, DeSantis spokeswoman Christina Pushaw told National Review.
So who is correct: the FDA or the state of Florida? The answer could be both and neither, as the scientific debate is nuanced, according to Dr. Myron Cohen, who helped develop the two monoclonal antibodies the FDA just determined are impotent against Omicron. Cohen is the director of the Institute for Global Health & Infectious Diseases and a professor of medicine, microbiology and immunology, and epidemiology at the University of North Carolina at Chapel Hill.
“The FDA is acting in the logical way that science has always worked. They are using the proper methodology, but it is also true that we have not proven that the drugs will fail in a clinical setting,” Cohen said.
The main impetus for the discontinuation was the rise of Omicron, the variant that now predominates in the United States, he said. While the original Wuhan strain and Delta variant were receptive to bamlanivimab/etesevimab and REGEN-COV, Omicron was not, at least in a tissue culture, Cohen noted.
“The only antibodies that were effective in a test tube against the new variant were AstraZeneca’s [Evusheld] and Virginia Biotechnology’s [ Sotrovimab]. They are active against Omicron,” he said. Evusheld and Sotrovimab both still have their emergency-use authorization.
Cohen said the scientific community is increasingly confident in the strength of the relationship between test tube and human results, which is called “surrogate of immunity.” If a drug shows promising in vitro data, it’s likely to work clinically, too. Therefore, the FDA’s decision was a matter of following protocol, he said.
During her press briefing Wednesday, White House press secretary Jen Psaki emphasized the alternative treatments the Biden administration is promoting and providing to Florida in lieu of the two discontinued drugs, namely anti-viral medications.
But applying the logic the FDA used to nix bamlanivimab/etesevimab and REGEN-COV, the anti-virals are not perfect either, particularly molnupiravir, produced by Merck, according to Jeremy Redfern, press secretary for the Florida Department of Health.
“I’d be happy to review any clinical data that was provided by the FDA to support their conclusions. Laboratory data is great and absolutely necessary, but as the pre-print referenced by Christina states, it does not tell us the benefits in a clinical setting. There is clinical data that shows Merck’s molnupiravir to be no better than placebo, but HHS just allocated Florida another 21,000 courses,” Redfern noted.
For molnupiravir, Cohen said the company completed a multinational clinical trial “as fast as it could,” and at the end it could declare only a 30 percent benefit. “The overall conclusion was that molnupiravir looked to be 30 percent effective, across all variants. We plan to do more studies to see if efficacy is limited to 30 percent,” Cohen added.
As for Psaki’s claim Wednesday that the two discontinued drugs “have side effects,” Cohen referred to his personal experience as a doctor at a massive hospital system of 13 facilities that has administered thousands of doses. “We haven’t seen a lot of side effects. It targets the virus, not the host, so it’s safe,” he said.
Molnupiravir, however, has risk factors for certain demographics, Cohen said. It probably should not be given to pregnant women, for instance, because it works through lethal mutagenesis. Lethal mutagenesis is a process by which the drug kills the virus by causing it to mutate. As a potential mutagen, the drug might hurt human tissues that are vulnerable to mutation, but this requires further study, he said.
“This drug [molnupiravir] is brand-new. It is not a drug for everybody; it may come with risk. This is the dialogue going around it as an alternative,” he added.
When it comes to pharmaceuticals, there’s always a cost-benefit analysis, Cohen said. To his knowledge, “There are no studies showing that you can kill Omicron with a drug that doesn’t work in a test tube. We’ve got to remember that there is time and money in giving drugs that don’t work for people.”
Then there’s the ethical dilemma. The FDA doesn’t want physicians offering drugs to patients that don’t work, Cohen said. With a drug under EUA, a different designation than a Biologics License Application, the patient must sign a consent agreement and be informed of its benefits. If the FDA believes it doesn’t work, then it’s doing a disservice to patients, he added.
Even though Cohen is an author on the papers for the two withdrawn drugs, he said his hospital voluntarily stopped giving them to patients long before the FDA officially revoked their authorization, given that Omicron accounted for 80 percent of all Covid-19 cases. “We didn’t think it was right as physicians,” he said.
Addressing reporters Wednesday, DeSantis mentioned that he’s aware of anecdotal evidence that patients have recovered shortly after receiving one of the two now-discontinued drugs. But while isolated personal testimonies can be compelling, they are insufficient to draw causation, Cohen said.
“It’s very difficult to sort out anecdotal evidence with Covid-19. You need a large number of subjects to prove benefit with a drug,” Cohen said. “If your elderly grandmother heals from the illness, it’s nearly impossible to conclude from a single anecdote whether it was God’s will or the REGEN-COV antibodies.”
“That’s why we do randomized control trials,” he said, in which there’s a large, randomized sample size with active agents and placebo agents.
“This is a repeat rodeo. The FDA is trying to protect patients who are vulnerable for receiving drugs that they don’t believe works. DeSantis wants the proof in the pudding. FDA believes it won’t work, but DeSantis wants them to show them it doesn’t work. It’s complicated.” Cohen said.
This an issue where scientific and political questions intersect, and both are valid, he suggested. Ultimately, however, the debate will become irrelevant in a few months, Cohen said. As new drugs are being manufactured or are already in the queue for EUA, they will replace the old ones, and it will no longer matter what the FDA is doing with bamlanivimab/etesevimab and REGEN-COV.
If he were the FDA or the governor, Cohen said, he would fight for rapid production of drugs that he knows will work.
“If you’re going to take away drugs that don’t work in a test tube, the FDA needs to expedite alternatives because we don’t have time to do massive, randomized control trials. We need to think about drug combinations or swapping in other antibodies,” he concluded.