FDA Declines EUA Request for Fluvoxamine for COVID-19 Treatment

The totality of the evidence led the FDA to determine that the criteria for issuing an EUA had not been met.

The Food and Drug Administration (FDA) has declined to issue an Emergency Use Authorization (EUA) for fluvoxamine maleate for COVID-19 treatment due to insufficient data supporting its use.

The submission for EUA included data from the phase 3 TOGETHER trial (ClinicalTrials.gov Identifier: NCT04727424), the phase 2 STOP COVID trial (ClinicalTrials.gov Identifier: NCT04342663), and a real-world study. The proposed use was for outpatient treatment of adults 24 years of age and older with positive test results of SARS-CoV-2 viral testing to prevent progression to severe COVID-19 and/or hospitalization.

The TOGETHER study included 1497 high-risk symptomatic adults who were randomly assigned 1:1 to receive fluvoxamine 100mg twice daily or placebo for 10 days. The STOP COVID study included 152 nonhospitalized adults who were randomly assigned 1:1 to receive fluvoxamine 100mg up to 3 times daily or placebo for 15 days. The real-world observational study included 113 patients who were offered fluvoxamine (50mg twice daily) on the same day that they tested positive for SARS-CoV-2.

Results from the TOGETHER study showed that treatment with fluvoxamine met the primary composite endpoint (reduction in emergency department [ED] visits due to clinical worsening of COVID-19 and hospitalization due to progression of COVID-19, up to 28 days after randomization), but the results were primarily driven by the reduction in ED visits lasting greater than 6 hours. The FDA noted that there were “uncertainties” as to whether the 6-hour timepoint could be considered a clinically meaningful threshold.

Moreover, the findings showed that when looking at clinically meaningful outcomes (ie, the proportion of patients experiencing hospitalizations or death), “the treatment benefit of fluvoxamine was not persuasive.”

When reviewing data from the STOP COVID and real-world studies, the Agency noted several design limitations, including small sample size and lack of randomization. Two additional studies, STOP COVID 2 (ClinicalTrials.gov Identifier: NCT04668950) and COVID-OUT (ClinicalTrials.gov Identifier: NCT04510194) also failed to show a benefit with fluvoxamine in patients with mild COVID-19 in the outpatient setting; these trials were terminated early for futility.

The totality of the evidence led the FDA to determine that the criteria for issuing an EUA had not been met as the data were insufficient to conclude whether the benefits of fluvoxamine outweighed its potential risks in nonhospitalized individuals with COVID-19. Evidence to support the proposed mechanism of action of fluvoxamine for COVID-19 treatment was also found to be lacking. However, the FDA did note that the existing data do suggest “further clinical investigation may be warranted”.

Fluvoxamine maleate, a selective serotonin (5-HT) reuptake inhibitor (SSRI), is currently indicated for the treatment of obsessions and compulsions in patients with obsessive compulsive disorder (OCD). 


Memorandum explaining basis for declining request for emergency use authorization of fluvoxamine maleate. News release. US Food and Drug Administration. Accessed May 17, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/EUA%20110%20Fluvoxamine%20Decisional%20Memo_Redacted.pdf

This article originally appeared on MPR