Why Won’t the FDA Let Doctors Prescribe Fluvoxamine for Covid?
Trials show it keeps patients from getting sicker, but the agency won’t approve its emergency use.
Article first appeared in the WSJ.
Ms. Finley is a member of the Journal editorial board.
The Food and Drug Administration is under attack for being too cozy with drugmakers, but there’s nothing wrong with regulators cooperating with private industry. That’s how we got Covid vaccines and therapies in record time. What’s rotten is that applications for new uses of generic drugs are reviewed under different standards than those for novel treatments. That’s what the FDA did this month when it rejected a Covid emergency-use authorization (EUA) application by doctors for the antidepressant fluvoxamine.
The media has derided some doctors as quacks for advocating off-label drugs like hydroxychloroquine and ivermectin. Early in the pandemic studies suggested the two anti-parasite drugs could be beneficial. David Boulware, an infectious disease specialist at the University of Minnesota, helped lead four of those trials. Yet he now strangely finds himself clashing with the FDA over its rejection of fluvoxamine.
In December, Dr. Boulware and several colleagues submitted an EUA application for fluvoxamine to treat non-hospitalized adult Covid patients. Three trials have shown the drug, typically prescribed for obsessive-compulsive and mood disorders, could prevent patients from becoming sicker, potentially because of its anti-inflammatory properties. One large randomized controlled trial in Brazil found that fluvoxamine reduced the risk of hospitalization or emergency care by 32%. Those who stuck to the treatment regimen were 66% less likely to be hospitalized and 91% less likely to die. The Lancet first published the findings in October.
A smaller trial in fall 2020 found that none of the 80 patients given fluvoxamine got worse compared with six of the 72 who received a placebo, four of whom were hospitalized. And in a real-world experiment at the Golden Gate Fields horse-racing track in Berkeley, Calif., none of the 65 workers who took the drug were hospitalized or had symptoms 14 days later. However, six of the 48 (12.5%) who didn’t were hospitalized, and more than half had lingering symptoms.
The FDA has issued many EUAs for novel Covid treatments based on far less evidence. Consider Merck-Ridgeback Biotherapeutics’ antiviral molnupiravir, which the FDA authorized in December after a single trial found it reduced hospitalization among high-risk patients by 31% and death by 89%.
In February the FDA authorized Eli Lilly’s monoclonal antibody bebtelovimab after a small study found it reduced viral load in a greater share of patients on the seventh day of treatment. It isn’t clear whether this translated into a meaningful clinical benefit, and the drug didn’t reduce hospitalizations or death compared with the placebo group.
The FDA justified its approval of bebtelovimab because it said there were few treatment alternatives. At the time there was a shortage of Pfizer’s antiviral Paxlovid—which was found to reduce risk of hospitalization or death by nearly 90%—and Merck’s antiviral molnupiravir. Paxlovid also interacts with dozens of drugs, including common cancer, anti-clotting and blood pressure medications, so many high-risk patients can’t take it. The FDA wasn’t wrong that there’s a need for more treatments.
Yet after sitting on the fluvoxamine application for nearly five months—most other EUAs have been approved within two—the FDA notified Dr. Boulware this month that “the treatment benefit of fluvoxamine was not persuasive when focusing on clinically meaningful outcomes.” How is prevention of severe illness not a clinically meaningful outcome?
The FDA quibbled that the “timing of the trials spanned different periods” of the pandemic and “demographics of the patient populations were not uniform.” Huh? These are trial strengths since they show the benefits can be generalized across different patient populations, settings and variants. That has proved not to be the case for monoclonal antibodies or even vaccines, which have become less effective against new variants.
The agency also said there are plenty of alternative treatments available. Never mind that the Biden administration has been warning it may need to ration antiviral and monoclonal treatments unless Congress coughs up billions to purchase more. A 10-day course of fluvoxamine costs about $5 compared with $500 to $700 for Paxlovid and molnupiravir. Monoclonals cost about $2,000.
Doctors also worry that Paxlovid could breed antiviral resistance as some patients report experiencing relapses after finishing a course. The more an antiviral is used, the more likely a virus will develop mutations that render the drug ineffective. That’s why the U.S. needs a broader arsenal of therapies—a point Dr. Boulware underlined in a rebuttal to the FDA.
Dr. Boulware assailed the agency’s “inconsistent logic” and its use of “different definitions for ‘hospitalization’ for big pharma vs. low-cost generic drugs.” He also criticized the FDA’s lack of clear guidance and expectations when dealing with medical researchers, which contrasts with its constructive working relationship with drugmakers.
Some conservatives accuse regulators of trying to protect drugmaker profits by limiting access to repurposed generics. There’s no evidence for this. The FDA in recent years has approved record numbers of generics. But the FDA doesn’t like to attract political controversy. And there’s no question other repurposed drugs like ivermectin have been controversial.
But by applying inconsistent regulatory standards and rejecting fluvoxamine despite its demonstrated benefits, the FDA may engender more political cynicism that undermines support for pharmaceutical innovations such as Covid vaccines.
A 10-day course of fluvoxamine costs about $5 compared with $500 to $700 for Paxlovid and molnupiravir. Monoclonals cost about $2,000.