FDA Rejects Emergency Use Authorization for Common and Inexpensive Antidepressant COVID-19 Treatment

After receiving an Emergency Use Authorization (EUA) application for fluvoxamine on December 21 of last year, the FDA decided to reject the EUA and took the time to provide a 27-page explanation detailing its reasoning. Despite the FDA stating that fluvoxamine does not provide significant enough results, researchers continue to ask why fluvoxamine did not receive EUA. 

Why the FDA Rejected Fluvoxamine’s EUA

The FDA’s memorandum describes fluvoxamine in two ways, the first being its use as a selective serotonin reuptake inhibitor approved for obsessive-compulsive disorder treatment and the second in its proposed use to treat COVID-19. 

The memo states that the rationale behind fluvoxamine’s potential to treat COVID-19 lies in its ability to bind to the sigma-1 receptor on immune cells and act as an agonist. This characteristic has the potential to reduce the production of inflammatory cytokines. Advanced COVID-19 patients often experience an increased number of pro-inflammatory cytokines throughout the body that can result in a series of biological events that can lead to organ failure or pneumonia. 

The FDA stated that the original EUA request was primarily based on the TOGETHER trial, a Brazil-based trial that studied the effect of fluvoxamine as early treatment in confirmed COVID-19 cases on the risk of emergency care and hospitalization. The trial included 741 participants who received a 100mg daily oral dose of fluvoxamine and 756 participants who received a placebo. 

The authors’ interpretation of the study was that fluvoxamine reduces the risk of hospitalization and emergency treatment for high-risk patients with COVID-19. However, the FDA made it clear they did not think the study provided sufficient enough evidence to support EUA. 

In addition to the TOGETHER trial, the FDA referenced the STOP COVID 2 trial and the COVID-OUT trial as further proof that fluvoxamine does not show enough evidence to support EUA. The FDA stated that both the STOP COVID 2 trial and COVID-OUT trial failed to demonstrate fluvoxamine’s benefit for adults with mild COVID-19, and the trials were terminated early for futility. 

Related Article: Vaccine Inequity, How Pandemic Becomes Endemic

Why Focus on Fluvoxamine?

As the COVID-19 pandemic continues to impact lives around the globe, it is apparent that even with vaccines, other early treatment options like fluvoxamine may have the potential to help mitigate the risk of advanced COVID-19. A few previously established alternatives have popped up over the last few years, like ivermectin, but have not gained FDA approval for lack of evidence. Others, like Pfizer’s Paxlovid, were developed from the ground up and received EUA from the FDA with relative ease.

One of the major benefits of leveraging a well-established drug for a different indication is its ubiquity in the market and decreased cost compared to alternatives. Dr. David Boulware, the researcher who submitted fluvoxamine’s EUA application, expressed his opinions on fluvoxamine’s potential to treat COVID-19 in his article in The Lancet. Dr. Boulware states that a wholesale pharmacy can acquire fluvoxamine at the cost of $4-66. He also says that at these prices, fluvoxamine could provide relief for low and middle-income countries worldwide that may not have access to vaccines or other costly treatments. 

Pfizer’s Paxlovid garnered a massive amount of attention upon EUA, and for a good reason; it is an effective drug to mitigate severe COVID-19 cases and hospitalizations. It comes with the caveat of being expensive, though, and advocates worldwide are questioning the access to the drug. In April, the World Health Organization released a statement praising Paxlovid and its potential benefits in healthcare but criticized Pfizer’s lack of transparency in Paxlovid’s pricing and availability. 

Pre-emptive treatments for high-risk patients diagnosed with COVID-19 will remain a central topic of COVID treatment. Determining which treatment options are most effective and available to a greater population will, in turn, be a part of that conversation. Vaccine inequity is an issue in the United States and worldwide, and other treatment options will follow suit without cost-effective options. 

Though many researchers argue in favor of fluvoxamine’s early-treatment potential, its time to shine is not today. Advocates like Dr. David Boulware may have the opportunity to apply for fluvoxamine’s EUA again one day, and hopefully, next time, with more convincing data for the FDA to analyze.

Related Article: Pfizer to Address COVID-19 Reinfection After Treated by Paxlovid

Author

Reed Slater