TThe Food and Drug Administration on Monday refused to approve a 30-year-old generic antidepressant as a treatment for Covid-19, which gave a big blow to a small group of doctors who have been organizing around the pill for several months, arguing that it could provide a cheap and accessible way to prevent hospitalizations and deaths both in the United States and around the world.
In an unusual two-sided Summary – The FDA generally does not disclose the rationale behind the rejections – regulators said doctors failed to provide sufficient evidence for the efficacy of the drug, called fluvoxamine.
The presentation was primarily based on a randomized, controlled trial of approximately 1,500 patients in Brazil, who found that patients receiving fluvoxamine early in the course of their disease were 32% less likely than patients receiving placebo to be admitted or in need of emergency treatment for at least six hours. There were also 17 deaths in the fluvoxamine group compared with 25 in the placebo group, although the difference was not statistically significant.
Fluvoxamine can be found at local pharmacies for around $ 4. When the clinical trial results came out last summer, they gave hope headlines about the prospect of using fluvoxamine as a cheap oral treatment against Covid-19 – at a time when other antiviral drugs were not yet on the market.
However, the FDA said Monday that it was uncertain that the six-hour cut-off used by the Brazil study was “a clinically meaningful threshold.”
Meanwhile, the results of hospitalizations and deaths alone were “not convincing.” Nor, regulators added, was a less randomized clinical trial conducted in the United States or a number of real-world studies because they were small, non-randomized, or used different endpoints.
Regulators also pointed to a few major randomized controlled trials that did not show the same benefit as the Brazil study did.
In a detailed rebuttal filed last week and shared with STAT, David Boulware, an infectious disease doctor at the University of Minnesota who led the push to get fluvoxamine approved as a Covid-19 treatment, said the FDA’s logic was “inconsistent”. . “
For example, he noted that the Merck and Pfizer trials for their oral antiviral drugs against Covid – molnupiravir and Paxlovid – were also not dependent on a conventional definition of hospitalization. Instead, they defined hospitalization as more than 24 hours of “emergency care.”
In an interview, Boulware said fluvoxamine could still have applications, although the Pfizer pill, Paxlovid, is far more effective and now fills pharmacies’ shelves. For example, many high-risk patients may not take Paxlovid because it may interact with a medicine they are taking to treat another condition.
Fluvoxamine may also be useful in middle- and low-income countries, where Pfizer and Merck pills are not yet widely available, Boulware said. The Merck pill reduces the risk of hospitalization from Covid-19 by about 30% according to the company’s clinical trials.
“It’s not my first choice as a doctor, but I should have the opportunity,” Boulware said.
Fluvoxamine was unusual among experimental Covid-19 drugs. Because it was generic, there were no drug companies that could profit from bringing it to regulators, which can be an expensive and time consuming process.
Instead, it was advocated by Boulware and a group of doctors and researchers who saw it as the easiest way to cheaply prevent Covid-19 at a time when the only drugs available to prevent hospitalization from Covid-19 were monoclonal antibodies, which must be injected or infused over an extended period of time.
Their efforts offered a test of how easily physicians could obtain a drug through regulators in a crisis without the support of patents or a drug sponsor.
With the new drugs now available, Boulware recognized that fluvoxamine is less essential. But he said it could have been hugely helpful during the Omicron rise in December, when he originally submitted the paperwork for approval.
At that time, neither Paxlovid nor molnupiravir were widely available, and the new variant had rendered most monoclonal individuals useless.
“This was extremely relevant back in December, when we had no Paxlovid, no antibodies,” he said. “Now it’s less relevant.”
Still, he said, more trials are underway. And if more evidence comes up, he and other researchers can resubmit it. Trials of other recycled medicines are also underway.