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The FDA has to nirmatrelvir-ritonavir (Paxlovid) for treating adult outpatients with mild to moderate COVID-19 who are at risk for severe disease, the agency announced on Thursday.

"Today's approval demonstrates that Paxlovid has met the agency's rigorous standards for safety and effectiveness, and that it remains an important treatment option for people at high risk for progression to severe COVID-19, including those with prior immunity," Patrizia Cavazzoni, MD, director of the FDA's Center for Drug Evaluation and Research, said in a statement.

Approval of the antiviral -- which helps ward off hospitalization and death in high-risk patients -- follows an endorsement from the agency's Antimicrobial Drugs Advisory Committee and was largely anticipated, despite some concerns about rebound cases and a host of drug-drug interactions, which garnered the drug a boxed warning on and for healthcare providers.

"Prescribers should review all medications taken by the patient to assess for potential drug-drug interactions and determine if other medicines that a patient may be taking require a dose adjustment, interruption and/or additional monitoring," according to the FDA. "Prescribers should consider the benefit of Paxlovid treatment in reducing hospitalization and death, and whether the risk of potential drug-drug interactions for an individual patient can be appropriately managed."

Nirmatrelvir-ritonavir was a critical component of President Biden's test-to-treat strategy during the pandemic. Given that the antiviral is indicated for use within 5 days of symptom onset, the program aimed to get it into the hands of patients testing positive quickly, and even allowed pharmacists to prescribe the drug directly to patients.

Millions of people with COVID-19, including Biden, have already taken the drug since its emergency use authorization (EUA) in late 2021, and multiple studies have confirmed the drug's benefit in high-risk groups, with studies in lower-risk groups typically showing little to no benefit.

In its approval notice, the agency said that previous packages distributed under the EUA will remain available for use. High-risk kids ages 12 and up will also continue to be eligible for the drug under the EUA, though the approval does not cover this group.

The agency further stipulated that nirmatrelvir-ritonavir is not intended for use as a preventive therapy either pre- or post-exposure to COVID (i.e., patients should have symptoms and a confirmed case before use).

Primary support for approval came from the final results of the EPIC-HR trial, which demonstrated an 86% reduction in the risk for hospitalization or death at 28 days versus placebo. Patients enrolled in the study included unvaccinated adults 18 and over with a medical condition(s) placing them at high risk for severe disease, or adults 60 and older with or without a chronic condition.

Of the 1,966 patients in the final analysis without SARS-CoV-2 antibodies at baseline, 0.9% of those who received nirmatrelvir-ritonavir and 6.5% of those on placebo were hospitalized due to COVID-19 or died through 28 days. Some benefit against hospitalization or death was also seen in that trial among people with prior immunity to the virus that causes COVID-19 as well (0.2% vs 1.7%, respectively).

And in the negative EPIC-SR study, which enrolled vaccinated patients with at least one risk factor for progression, a non-significant risk reduction in hospitalization and death was observed in the nirmatrelvir-ritonavir arm.

Data in those trials suggested that COVID-19 rebound cases occurred in a similar proportion of nirmatrelvir-ritonavir and placebo patients, leading the agency to conclude that "there is not a clear association" with the available evidence.

Beyond that, the FDA noted impaired sense of taste and diarrhea as the most common side effects with treatment.

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