Which COVID Outpatient Therapy Should Clinicians Reach For?

Due to the Omicron variant and the short supply of COVID therapeutics, NIH recommends certain therapies over others for patients at high risk of progressing to severe COVID, said federal officials on a call with clinicians Wednesday.

In order of preference, clinicians should use the oral antiviral nirmatrelvir-ritonavir (Paxlovid), the monoclonal antibody sotrovimab, the IV antiviral remdesivir (Veklury) and finally, the oral antiviral molnupiravir, said Alice Pau, PharmD, of the NIH COVID-19 Treatment Guidelines panel.

While the drugs were ranked from 1 to 4, she noted that nirmatrelvir-ritonavir, sotrovimab, and IV remdesivir three times a day all had similar clinical efficacy, with a relative risk reduction of 88%, 85%, and 87% in hospitalizations and deaths, respectively, versus placebo. However, molnupiravir, with its 30% efficacy, should be used only if the other three choices are not available, Pau noted.

She cited the sweeping changes made to the NIH guidelines for COVID therapies at the end of December, namely due to the fact that bamlanivimab + etesevimab and casirivimab + imdevimab are no longer recommended for outpatients, as the agents have not shown in vitro efficacy against the Omicron variant.

Pau said that while the clinical efficacy of the agents was the most important factor in the panel’s recommendations, the logistics of delivering the drugs (taken orally vs IV infusion), duration, populations of interest, and the drug interaction potential also played a role in the panel’s reasoning.

For example, she said that nirmatrelvir-ritonavir, sotrovimab, and remdesivir are all authorized or approved for ages 12 and up, while molnupiravir is authorized only for adults ages 18 and up.

Supply of therapeutics has been a problem, although Colin Shepard, MD, CDC liaison to the Office of the Assistant Secretary for Preparedness and Response, said that this week, the federal government provided 100,000 courses of nirmatrelvir-ritonavir, and 400,000 of molnupiravir.

“Given the limited drug supplies, the highest priority should be given to patients with the highest risk of progression to severe disease,” Pau said.

She reviewed the patient groups where the drugs can be administered, in order of who might receive the most benefit:

• Immunocompromised people who don’t mount a good response to vaccines, unvaccinated adults over age 75, or unvaccinated adults over age 65 with clinical risk factors

• Unvaccinated people under age 65 without risk factors

• Vaccinated adults over age 75 or vaccinated adults over age 65 with risk factors

• Vaccinated adults over age 65 without risk factors or vaccinated adults under age 65 with risk factors

Clinicians were the most interested in nirmatrelvir-ritonavir — namely that because it contains a course of the protease inhibitor ritonavir, it could lead to the development of HIV resistance. FDA staff noted that patients with HIV who are not on treatment and do not have an undetectable viral load should consult with their healthcare provider when taking nirmatrelvir-ritonavir.

Pau also said the most important step in prescribing nirmatrelvir-ritonavir is determining if there will be any drug/drug interactions, specifically with ritonavir and the patient’s current medications. She added that because it is a 5-day course, it’s “different than taking the drug chronically.”

“Get that list of medications the patient is on, look through them, and see if there’s any potential interaction,” she noted.

CDC staff also confirmed that there are no data yet on whether patients on antivirals can discontinue isolation sooner, as there has been little research on the effect of antivirals on SARS-CoV-2 transmission.