Why Trump's 'Cure' Isn't Ready for Approval
Shortly after President Trump touted Regeneron Pharmaceuticals’ experimental antibody cocktail treatment for COVID-19 as a “cure,” both Regeneron and Eli Lilly and Company applied to the U.S. government to open their antibody treatments to the public.
Regeneron’s treatment, REGN-COV2, contains two antibodies: one from a person who had recovered and the other from a mouse genetically modified to have a human immune system. Eli Lilly’s treatment, LY-CoV555, uses an antibody from one of the first patients in the U.S. to recover.
Both of these treatments contain antibodies that are meant to attach to the “spike protein” of the SARS-CoV-2 virus. (A spike protein mediates the virus’s entry into cells.)
Antibodies are proteins that our immune cells and B cells make to fight off infection. There was a strong push months ago for “convalescent plasma”—which is plasma donated by persons who have recovered from COVID-19 – in the hopes that the antibodies that their bodies created to fight the virus could help those with current infections through transfusions. But as researchers learn more about COVID-19, they’re trying to pick out the most important antibodies that attach to the virus and engineer them to make them more effective. Neither company has finished its clinical trials yet, but both argue that the pandemic is so urgent that the treatments should be made available immediately.
However, Aruna Subramanian, MD, an infectious disease physician at Stanford Health Care and site principal investigator for a number of COVID-19 drug trials, is skeptical about that. She told Medical Daily that both treatments are thought to be effective, but that they’re still “very much under study.” And she would know, considering she’s the principal investigator for Stanford’s Regeneron antibody cocktail inpatient trial.
“We’re looking at three arms,” she said. “People will either get the high dose of the monoclonal antibody, the lower dose, or the placebo. And they’re blinded -- we don’t know what they're getting, and the patient doesn’t know what they’re getting. And then we’re following the viral load through swabs of nasal passages and bloodwork.”
The data that both companies have so far come from outpatients with mild to moderate disease. The inpatient studies have not yet enrolled enough patients or analyzed enough data to announce any findings. Dr. Subramanian said that her study has thus far enrolled a few hundred patients, not all of whom have survived, and she doesn’t know who has received medications (or at what dose) versus placebos.
So, at the moment, there is preliminary evidence that both drug treatments do help patients with mild to moderate cases: Their viral load goes down faster, symptoms resolve faster, and they’re less likely to need hospitalization. The treatments have been most helpful in patients whose immune systems hadn’t yet mounted a response to the virus. No one yet knows the effect on the more severe cases, nor of the long-term side effects of the medications, but the infusions themselves have not caused serious immediate side effects.
Dr. Subramanian said that the evidence the U.S. Food and Drug Administration (FDA) will have available to evaluate these emergency applications is scant. “What’s been released [from Regeneron] is only 275 patients, and even that is only top-line results. The full FDA approval process is a much more in-depth process. For this application, they do sort of a superficial look and decide if giving this sort of a conditional emergency authorization has enough benefit to society.”
Phase 3 studies like this normally have significantly higher numbers; by comparison, Moderna, AstraZeneca and Pfizer are all looking to enroll 30,000 subjects in their Covid-19 vaccine trials, and Johnson & Johnson is recruiting 60,000 subjects around the world. Only 25 to 30% of drugs that make it to this stage move on to approval and the final stage: studying the drug in real-world use.
The FDA doesn’t have to give blanket approval. For example, the antiviral drug remdesivir was granted emergency authorization only for inpatients. However, Dr. Subramanian hopes that won’t happen with the new applications.
For one thing, if they are approved for emergency use it will make it much harder to enroll patients in the clinical studies where they don’t know what treatment they’re getting. Why would someone sign up to potentially get a placebo or an unknown dose in a study if they can just get a prescription for the medication after it is approved?
Losing out on enrollees for further studies would hobble researchers’ efforts to collect important information: how effective (or not) is each drug, at what dose, with what side effects, in which populations, and at what timing and frequency? For instance, at this time, it’s not known whether there’s any need for the high doses or whether the low dose is just as effective.
She understands that President Trump’s bold remarks after his successful treatment have pushed this emergency request forward, but cautions that major drug decisions should never be based on one person’s outcome. Besides, in this case, there are too many variables to say with any certainty whether or how much Regeneron’s treatment helped.
“We don’t know when [the president] last tested negative; we don’t know when it started. He received other treatments, they never told us what his lung imaging scans looked like or the severity of his case, and these are all things that need to be studied.”
Dr. Subramanian hopes the FDA will deny the applications for now, allowing the studies to continue for a few more months so the data can be properly gathered and reviewed.
“Let's study this further and see where it really belongs before pushing something through. I think that would be the most responsible thing,” she said.
Jenna Glatzer (www.jennaglatzer.com) is the author or ghostwriter of more than 30 books, including Celine Dion’s authorized biography. Her latest work is Gratitude in Motion: A True Story of Hope, Determination, and the Everyday Heroes Around Us with Colleen Kelly Alexander.