Disclosures: Healio could not confirm relevant disclosures for Boulware at the time of publication.
The FDA declined a request to authorize an inexpensive generic antidepressant and obsessive-compulsive disorder medication for emergency use as an outpatient treatment for COVID-19.
In a 25-page memo, the FDA said there were insufficient data showing that the medication, fluvoxamine maleate, “may be effective in the treatment of nonhospitalized patients with COVID-19 to prevent progression to severe disease and/or hospitalization.”
The request for an emergency use authorization was based on data from the randomized placebo-controlled TOGETHER trail conducted in Brazil, which demonstrated that fluvoxamine reduced the need for hospitalization among high-risk patients with COVID-19, researchers reported.
The researchers argued that the medication, which costs around $4 for a 10-day regimen, could benefit lower-income countries with less access to COVID-19 vaccines and therapies.
The FDA noted that the trial met its primary endpoint but said “the results were primarily driven by a reduction in the emergency department visits lasting greater than 6 hours, and there are uncertainties about the assessment of this endpoint and whether the 6-hour timepoint represents a clinically meaningful threshold.”
It said the trial failed to demonstrate a “persuasive” treatment benefit “when focusing on clinically meaningful outcomes such as proportion of patients experiencing hospitalizations or hospitalizations and deaths,” and that three other trials and real-world data were either limited in their design or failed to demonstrate a benefit of fluvoxamine for COVID-19.
The physician who submitted the EUA request for fluvoxamine this past December said he was “disappointed that FDA holds generics to different standards” than medications supported by large pharmaceutical companies — “in this case using [a] different definition of endpoints” for what a COVID-19-related hospitalization is.
David Boulware, MD, MPH, professor of medicine in the division of infectious diseases and international medicine at the University of Minnesota Medical School, said pharmaceutical companies are allowed to define hospitalization as “hospitalization or [more than] 24 hours of acute care” whereas applications for genetic medications can only use “hospitalization.”
“The two-tiered standard seems overtly wrong to me,” Boulware tweeted.
“During the EUA process, when FDA requested ‘hospitalization’ only data on Feb 1, in my response, I pointed out that FDA was being inconsistent with the FDA treatment of molnupiravir” — Merck’s antiviral, which received an EUA in December — “which used ‘hospitalization or [greater than] 24hrs acute care.’ (They didn’t care),” Boulware continued.
In addition to molnupiravir, the FDA in December also issued an EUA for Pfizer’s oral antiviral for COVID-19, Paxlovid, which is now available at many US pharmacies.
“Ultimately, fluvoxamine is less relevant in the USA now during the vaccine era with Omicron,” Boulware tweeted. “But, in low and middle income countries globally, most people worldwide do not have access to effective therapies. It’s good to give options & Steer away from ineffective therapies.”