The Food and Drug Administration is under attack for being too comfortable with drugmakers, but there’s nothing wrong with regulators working with private industry. This is how we got Covid vaccines and therapies in record time. What’s fishy is that applications for new uses of generic drugs are reviewed to different standards than those for novel treatments. That’s what the FDA did this month when it denied a Covid Emergency Use Authorization (EUA) application by doctors for the antidepressant fluvoxamine.
The media has derided some doctors as quacks for endorsing off-label drugs like hydroxychloroquine and ivermectin. Early in the pandemic, studies suggested the two drugs could be beneficial against parasites. David Boulware, an infectious disease specialist at the University of Minnesota, helped direct four of those studies. But now he’s oddly at odds with the FDA over the rejection of fluvoxamine.
In December, Dr. Boulware and several colleagues submitted an EUA application for fluvoxamine to treat non-hospitalized adult Covid patients. Three studies have shown that the drug, which is typically prescribed for OCD and mood disorders, may be able to prevent patients from getting sicker thanks to its anti-inflammatory properties. A large randomized controlled trial in Brazil found that fluvoxamine reduced the risk of hospitalization or emergency treatment 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 results in October.
A smaller study in the fall of 2020 found none of the 80 patients given fluvoxamine got worse, compared with six of the 72 given a placebo, four of whom were hospitalized. And in a real-world experiment at Golden Gate Fields horse track in Berkeley, California, 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 did not were hospitalized and more than half had persistent symptoms.
The FDA has issued many EUAs for novel Covid treatments based on far less evidence. Consider Merck-Ridgeback Biotherapeutics’ antiviral drug molnupiravir, which the FDA approved in December after a single study found it reduced hospitalizations by 31% and deaths by 89% in high-risk patients.
In February, the FDA approved Eli Lilly‘s
monoclonal antibody bebtelovimab after a small study found it reduced viral loads in a larger proportion of patients by day seven of treatment. It’s not clear if this resulted in a meaningful clinical benefit, and the drug didn’t reduce hospitalizations or deaths compared to the placebo group.
The FDA justified the approval of bebtelovimab with the fact that there are only a few treatment alternatives. At the time there was a shortage of Pfizer‘s
the antiviral Paxlovid – which reduces the risk of hospitalization or death by almost 90% – and Merck’s antiviral molnupiravir. Paxlovid also interacts with dozens of drugs, including common cancer, coagulation, and blood pressure drugs, leaving many high-risk patients unable to take it. The FDA wasn’t wrong that more treatments are needed.
But after sitting on fluvoxamine use for nearly five months — most other EUAs were approved within two months — the FDA told Dr. Boulware this month that “the treatment benefit of fluvoxamine was not convincing when focusing on clinically meaningful outcomes.” How is prevention of major disease not a clinically meaningful outcome?
The FDA criticized that the “timing of the studies spanned different periods” of the pandemic and “the demographics of the patient populations were not consistent.” huh? These are study strengths as they show that the benefits can be generalized to different patient populations, settings, and variants. This does not apply to monoclonal antibodies or even vaccines, which have lost effectiveness against new variants.
The agency also said there are many alternative treatments. Never mind that the Biden administration has warned that it may have to ration antiviral and monoclonal treatments unless Congress coughs up billions to buy more. A 10-day course of fluvoxamine costs about $5 compared to $500 to $700 for Paxlovid and molnupiravir. Monoclonals cost around $2,000.
Doctors also worry that Paxlovid could induce antiviral resistance, as some patients report relapses after completing a course. The more frequently an antiviral drug is used, the more likely it is that a virus will develop mutations that render the drug ineffective. Because of this, the US needs a broader arsenal of therapies – a point Dr. Boulware in a rebuttal to the FDA.
dr Boulware criticized the agency’s “inconsistent logic” and its use of “different definitions of ‘hospitalization’ for big pharma versus low-cost generics.” He also criticized the FDA’s lack of clear guidance and expectations when dealing with medical researchers, which contrasts with their constructive working relationships with drugmakers.
Some conservatives accuse regulators of protecting drugmakers’ profits by restricting access to repurposed generics. There is no evidence for that. The FDA has approved a record number of generic drugs in recent years. But the FDA doesn’t like stirring up political controversy. And there’s no question that other repurposed drugs like ivermectin have been controversial.
But by applying inconsistent regulatory standards and rejecting fluvoxamine despite its proven benefits, the FDA could incite more political cynicism that undermines support for pharmaceutical innovations like Covid vaccines.
Ms. Finley is a member of the Journal’s editorial board.
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https://www.wsj.com/articles/why-wont-the-fda-let-doctors-prescribe-fluvoxamine-for-covid-drug-approval-ivermectin-11653923709 Why Won’t the FDA Let Doctors Prescribe Fluvoxamine for Covid?