The FDA announced this week that it is limiting use of two monoclonal antibody drugs for Covid that do not work against the Omicron variant — a step that many thought was overdue. Acting FDA Commissioner Janet Woodcock spoke with STAT about what comes next for the regulation of Covid drugs and vaccines.
This interview has been edited for clarity.
So let’s start with how the FDA decided to limit the use of these two monoclonal antibody drugs for Covid. Can you walk us through the data that the agency relied on?
Let’s start with the understanding that I was the therapeutics lead for Operation Warp Speed, and we focused on monoclonal antibodies really early. We expected that if a variant occurred that was far enough away from the virus the monoclonals were made against, that it would be able to escape the monoclonals. And so assays were set up with something called pseudovirus assays, that are pretend virus particles, and real virus assays, where you see if the antibody can neutralize the virus. And that’s really the basis for how these work and how we pick the antibodies to start with.
So when the different strains came along, Delta and so forth, they would be tested in these assays to make sure they still had activity and could neutralize these variants. When Omicron came along, publications quickly came out and the government testing showed the same thing, and the company’s testing showed the same thing, that these monoclonal antibodies, particularly the Regeneron one and the Lilly monoclonals, did not neutralize the virus. So that would mean it wouldn’t work against the strain.
One of the criticisms that we’ve heard this week is that there’s no clinical data from human trials and that the laboratory data hasn’t been peer-reviewed. Do these criticisms hold any water with you or the agency?
Well, there have been preliminary, peer-reviewed publications published, and the government has done assays, as I said, that we’ve set up long ago to make sure, as variants came along, that the monoclonal and the vaccine serum would remain robust against them. And so we have a really robust amount of scientific data, including from the companies themselves. Don’t forget, they discovered these monoclonals and they set up assays to monitor them. And they also say that these monoclonals don’t neutralize Omicron. So there’s evidence from both government laboratories, the companies, and then independent academic laboratories. And just from the sequence of this variant itself, which we know has a lot of differences in the receptor binding domain, which is the place where these monoclonals grab on to the virus.
Outside of the scientific conversation, we’ve seen some opposition to this decision to limit the use of these antibodies. That seems to be more practical. The argument that we’ve heard from officials in Florida and others is that other treatment options for Covid-19 are so scarce that using one of these drugs, despite its limitations, would be better than nothing. Is that a salient point in your mind?
Well, as you know, I’ve long been head of the drug center at FDA and there’s no free lunch with drugs. They all have harm as well as benefits. We’re also having tremendous staffing shortages of health care personnel, and they’re required to administer these monoclonals because sometimes you can have anaphylaxis, you have to start an IV. It isn’t a simple pill or procedure. There are other alternatives. FDA recently approved remdesivir for infusion in outpatients, and it has a very good treatment effect against this variant. It is IV also, but it is three IV infusions on successive days, so it’s a little more complicated, but that’s commercially available right now. And of course, there is a monoclonal that does neutralize the virus, the GSK-Vir monoclonal, but it is in short supply.
Both Lilly and Regeneron say they have next-generation drugs in development that do hold up against Omicron, and Lilly says it’s completed Phase 2 trials and that it has hundreds of thousands of doses already made. On Twitter this week, former FDA Commissioner Dr. Scott Gottlieb called for a regulatory pathway that would authorize new antibodies quickly based on human safety data and lab evidence of effectiveness against new variants. Is that something that’s on the table under consideration here?
Certainly. In February, FDA published guidance for industry on what we would do, for example, if variants escaped diagnostic tests and how we would monitor for that. If the variants escaped vaccines, what would we do there to get additional vaccine available from the same platform, and what we do about monoclonals. And so there we talk about what companies would need to do, and it is a very streamlined program compared to what was done originally with the monoclonal antibodies.
Pivoting to vaccines: A lot of people want to know what the FDA is doing about vaccines for kids under 5. Pfizer had a little bit of a setback and is now adding a third dose. So it sounds like those results may be available late March or early April. Moderna has said that data for kids 2 to 5 will be ready in March. Do you expect that we will eventually have a vaccine for that age group kids two to five? And is there a sense of urgency around this with the FDA?
There’s definitely a sense of urgency, and we’re really working extremely closely with the developers on the younger age group. As you know, for the younger age group, you usually need a different dosage form, a smaller dose. And also we need some information in those little children and babies before we go ahead and just authorize it based on adults or teenagers or younger children. But there is a sense of urgency, and we’ve certainly heard from many, many parents who would like to immunize their children.
Thinking more broadly about the FDA’s role in the pandemic response, the issue we discussed in Florida with monoclonal antibodies wasn’t the first time that we’ve seen states openly question or view FDA decisions with some skepticism. We saw quite a bit of it in 2020 with the authorization of Covid-19 vaccines, for instance. Had you seen this kind of pressure at any point before in your career at FDA? And do the objections from states in this matter kind of have influence over how the agency conducts itself?
To answer your second question, no, we conduct ourselves according to the statutes and the regulations, and our role in overseeing product development and marketed products. In the past, we have seen states might want to go a different direction or have a different point of view than the federal government on things, for example cancer-causing agents in California. And you need to talk and work these things out as best you can.
This, of course, is higher-profile because all the states are so involved in response to the pandemic. So naturally they would have their own opinions and naturally, there would be some differences, because there’s a great deal of uncertainty here. When we started the monoclonal, and this is what’s kind of ironic, I was still at Operation Warp Speed then and we had gotten these monoclonals out and we had quite a bit of difficulty talking people into administering them at first. So, it cuts both ways. I’d say.
So just one closing question. You’ve been with the FDA since 1986 and of course, in the top job now, as you know, Robert Califf makes his way through the confirmation process. What’s next for you?
Well, that’s not something I’m really ready to talk about. I’m certainly going to oversee an orderly transition at FDA, and then we can have more conversations about that. But the handoff is in the middle of a pandemic and all these different things that’s going on. I’m definitely going to make sure we have a very robust hand-off.
To listen to the full interview, and more, listen to Episode 194 of “The Readout LOUD” podcast.
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