The FDA has rejected the application, explaining the COVID-19 treatment benefit of the drug was “not persuasive” in the TOGETHER study that was the basis of the EUA application.
The randomized, double-blind study had a composite endpoint consisting of a reduction of emergency room visits due to worsening COVID-19 infection and hospitalization resulting from COVID-19 up to 28 days after randomization.
The study concluded that fluvoxamine reduced COVID-19 hospitalizations by as much as 30%.
Although the study met its primary endpoint, FDA noted that “the results were primarily driven by a reduction in the emergency department visits lasting greater than 6 hours.”
The agency added that “there are uncertainties about assessing this endpoint” and questioned whether the 6-hour time threshold was “a clinically meaningful threshold.”
FDA went on to raise doubts about the design of the TOGETHER study.
Finally, the agency noted that two other trials, known as STOP COVID 2 and COVID-OUT, “failed to demonstrate a benefit with fluvoxamine in adults with mild COVID-19 in the outpatient setting, and both were terminated early for futility.”
In 1994, fluvoxamine became the first FDA-approved SSRI.
The logic for using the drug for COVID-19 is that it inhibits the sigma-1 receptor (SR1) associated with inflammation, which influences the body’s COVID-19 response.
It was developed by Kali-Dupha, part of Solvay Pharmaceuticals, which Abbott Laboratories acquired for €4.5 billion in 20210.
It is currently FDA-approved for treating obsessive-compulsive disorder in individuals at least 8 years old.
Boulware responded to FDA critiquing the consistency of the agency’s definition of “hospitalization” for new drugs such as the COVID-19 antiviral Paxlovid from Pfizer compared to generic drugs.
In an interview with MedPage Today, Boulware observed that Merck & Co.’s molnupiravir appeared to have similar treatment efficacy as fluvoxamine, which was authorized for emergency use.
Boulware filed for emergency use authorization before FDA authorized the use of the COVID-19 antivirals molnupiravir and Plaxovid.