The FDA’S Antimicrobial Drugs Advisory Committee (ADAC) voted 16 to 1 on Thursday in favor of Pfizer’s antiviral Paxlovid (nirmatrelvir and ritonavir) for the treatment of mild-to-moderate COVID-19 in adults who are at high risk for progression to severe COVID-19, including hospitalization or death.

The expert panel was overwhelmingly supportive of the FDA granting traditional approval to a five-day course of Paxlovid in adults. If the agency agrees, Paxlovid could soon become the first oral approved treatment for mild-to-moderate COVID-19.

“Besides oxygen, Paxlovid has been the single most important treatment tool in this epidemic,” and it continues to be pivotal for those who are unvaccinated, elderly, and/or immunocompromised,” said Richard Murphy, chief of infectious diseases at the Veterans Affairs White River Junction Medical Center in White River Junction, Vt.

As for safety, most on the panel agreed Paxlovid was safe, except for some drug interactions that can put a patient at risk. The panel agreed that if Paxlovid gets full approval, physicians will need to be vigilant about potentially dangerous drug interactions.

Paxlovid, which renders SARS-CoV-2 incapable of replicating, got emergency use authorization (EUA) on Dec. 22, 2021, for patients who are at high risk for progression to severe COVID-19 (DID, Dec. 23, 2021).

The only other treatment option that has traditional FDA approval for non-hospitalized adults with mild-to-moderate COVID-19 at high risk for severe COVID-19 is Gilead’s Veklury (remdesivir) for injection.

Besides Paxlovid, only one other oral COVID-19 treatment has an EUA: Merck’s Lagevrio (molnupiravir). However, the National Institutes of Health (NIH) guidelines currently recommend only using molnupiravir when Paxlovid and remdesivir are not available or cannot be given.

To support the proposed Paxlovid indication, Pfizer conducted three phase 2/3 trials.

The two treatment trials enrolled in 2021 — before omicron, which since 2022 has been the dominant SARS-CoV-2 strain — and included very few immunocompromised subjects.

One trial showed high efficacy for unvaccinated patients at high risk for complications. The FDA said the relevance of these results is in question as now 91 percent of the total U.S. adult population and 95 percent of those 65 and older have gotten at least one COVID-19 vaccine dose or were previously infected with COVID-19.

A second trial had lackluster effects on symptom alleviation but subjects had a lower rate of COVID-19-related hospitalizations or deaths from any cause than did the control group.

A third trial tested Paxlovid for post-exposure prophylaxis of symptomatic SARS-CoV-2 infection in adult household contacts of people with symptomatic COVID-19, and failed to demonstrate any meaningful difference when compared to placebo.

Pfizer has other trials under way to monitor Paxlovid’s efficacy.

FDA presenters noted that, despite the lack of clinical trial data to directly determine the clinical efficacy of Paxlovid in high-risk adults infected with the omicron variant, “nonclinical and clinical data demonstrate that Paxlovid retains antiviral activity against omicron.”

The FDA added that it’s aware of five retrospective cohort studies using real-world evidence showing that Paxlovid is effective against the omicron variant. — Suz Redfearn