FDA Authorises First Oral Antiviral for Treatment of COVID-19

December 22, 2021

The US Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for

nirmatrelvir tablets and ritonavir tablets, co-packaged for oral use (Paxlovid) for the treatment of mild-to-moderate coronavirus disease (COVID-19) in adults and paediatric patients aged 12 years and older weighing at least 40 kg (88 lbs) with positive results of direct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing, and who are at high risk for progression to severe COVID-19, including hospitalisation or death.

The new treatment is available by prescription only and should be initiated as soon as possible after diagnosis of COVID-19 and within 5 days of symptom onset. 

“Today’s authorisation introduces the first treatment for COVID-19 that is in the form of a pill that is taken orally -- a major step forward in the fight against this global pandemic,” said Patrizia Cavazzoni, MD, FDA’s Center for Drug Evaluation and Research, Rockville, Maryland. “This authorisation provides a new tool to combat COVID-19 at a crucial time in the pandemic as new variants emerge and promises to make antiviral treatment more accessible to patients who are at high risk for progression to severe COVID-19.” 

Nirmatrelvir/ritonavir tablets are not authorised for the pre-exposure or post-exposure prevention of COVID-19 or for initiation of treatment in those requiring hospitalisation due to severe or critical COVID-19.

Nirmatrelvir/ritonavir tablets are not a substitute for vaccination in individuals for whom COVID-19 vaccination and a booster dose are recommended.

Nirmatrelvir inhibits a SARS-CoV-2 protein to stop the virus from replicating, and ritonavir slows down nirmatrelvir’s breakdown to help it remain in the body for a longer period at higher concentrations.

The treatment is administered as 3 tablets (2 tablets of nirmatrelvir and 1 tablet of ritonavir) taken together twice daily for 5 days, for a total of 30 tablets. Treatment is not authorised for use for longer than 5 consecutive days. 

The issuance of an EUA is different from an FDA approval. In determining whether to issue an EUA, the FDA evaluates the totality of scientific evidence available and carefully balances any known or potential risks with any known or potential benefits of the product. Based on the FDA’s review of the totality of the scientific evidence available, the agency has determined that it is reasonable to believe that nirmatrelvir/ritonavir tablets may be effective for the treatment of mild-to-moderate COVID-19 in authorised patients. The agency has also determined that the known and potential benefits of nirmatrelvir/ritonavir tablets, when used consistent with the terms and conditions of the authorisation, outweigh the known and potential risks of the product.

The primary data supporting this EUA are from EPIC-HR, a randomised, double-blind, placebo-controlled clinical trial studying nirmatrelvir/ritonavir tablets for the treatment of non-hospitalised symptomatic adults with a laboratory confirmed diagnosis of SARS-CoV-2 infection. Patients were adults aged 18 years with a prespecified risk factor for progression to severe disease or were aged 60 years and older, regardless of prespecified chronic medical conditions. None of the patients in the study had received a COVID-19 vaccine and had not been previously infected with COVID-19. The main outcome measured in the trial was the proportion of people who were hospitalised due to COVID-19 or died due to any cause during 28 days of follow-up. Nirmatrelvir/ritonavir tablets significantly reduced the proportion of people with COVID-19 related hospitalisation or death from any cause by 88% compared with placebo among patients treated within 5 days of symptom onset and who did not receive COVID-19 therapeutic monoclonal antibody treatment. In this analysis, 1,039 patients had received nirmatrelvir/ritonavir tablets, and 1,046 patients had received placebo and among these patients, 0.8% who received nirmatrelvir/ritonavir tablets were hospitalised or died during 28 days of follow-up compared with 6% of the patients who received placebo.

The safety and effectiveness of nirmatrelvir/ritonavir tablets for the treatment of COVID-19 continue to be evaluated.

Possible side effects of nirmatrelvir/ritonavir include impaired sense of taste, diarrhoea, high blood pressure, and muscle aches.

Using nirmatrelvir/ritonavir tablets in people with uncontrolled or undiagnosed HIV-1 infection may lead to HIV-1 drug resistance.

Ritonavir may cause liver damage, so caution should be exercised when giving the combination treatment to patients with pre-existing liver diseases, liver enzyme abnormalities or liver inflammation.

Nirmatrelvir/ritonavir tablets are not recommended in patients with severe kidney or severe liver impairment. In patients with moderate renal impairment, a reduced dose is needed.

Using nirmatrelvir/ritonavir tablets at the same time as certain other drugs may result in potentially significant drug interactions. For a complete list of drugs that should not be taken in combination with nirmatrelvir/ritonavir tablets, see the fact sheet for healthcare providers.

Reference: https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-first-oral-antiviral-treatment-covid-19

SOURCE: US Food and Drug Administration