Paxlovid and Molnupiravir | A new front in the battle against the pandemic

The anti-viral drugs developed by Pfizer and Merck mark a significant advance in the management of the COVID-19 outbreak

Updated - December 26, 2021 12:21 am IST

Published - December 26, 2021 12:11 am IST

Illustration: R. Rajesh

Illustration: R. Rajesh

The U.S. Food and Drugs Administration (FDA) has given an Emergency Use Authorisation (EUA) to two drugs: Paxlovid, a treatment regimen developed by Pfizer Inc for treating mild-to-moderate Covid-19 in adults and children 12 years and older, who are likely to be at greater risk for severe infection, and Molnupiravir, developed by Merck and Ridgeback Biotherapeutics to treat mild-to-moderate COVID-19 in adults who are at risk for severe disease.

Paxlovid is a three-pill combination, this is widely believed to be the first treatment that can be administered outside hospital settings and therefore represents a significant advance in the management of the COVID-19 pandemic. “There are no adequate, approved and available alternatives to Paxlovid for the treatment of COVID-19,” the US FDA said in a statement.

Molnupiravir is a medication that works by introducing errors into the SARS-CoV-2 virus’ genetic code, which prevents the virus from further replicating. It is administered as four, 200 milligram capsules taken orally every 12 hours for five days, for a total of 40 capsules. It will be available by prescription only and is intended to be used more restrictively, given its mechanism of action.

In a statement, Pfizer said data from its clinical trial suggested that its regimen was nearly 90% effective in preventing hospitalisations and deaths in patients at high risk of severe illness. The drug remained effective against the Omicron variant. In the trial that consisted of about 2,200 people, some of whom got Paxlovid and some who didn’t — none who got the Pfizer treatment died, compared with 12 deaths among placebo recipients.

The primary data supporting authorisation for Molnupiravir was from MOVe-OUT, a randomised, double-blind, placebo-controlled clinical trial. The main outcome measured in the trial was the percentage of people who were hospitalised or died due to any cause during 29 days of follow-up. Of the 709 people who received Molnupiravir, 6.8% were hospitalised or died within this time period compared to 9.7% of the 699 people who received a placebo.

Paxlovid consists of nirmatrelvir, which inhibits a SARS-CoV-2 protein to stop the virus from replicating, and ritonavir, which slows down nirmatrelvir’s breakdown to help it remain in the body for a longer period at higher concentrations. Ritonavir is an anti-HIV drug and was made by Abbot Inc and is currently off-patent. Nirmatrelvir is yet to be patented though the company has set the process in motion.

Paxlovid is administered as three tablets (two tablets of nirmatrelvir and one tablet of ritonavir) taken together orally twice daily for five days, for a total of 30 tablets. Paxlovid is not authorised for use for longer than five consecutive days. It can be administered at home unlike other treatments such as the Merck-made Molnupiravir that is a monoclonal antibody treatment and needs to be administered intravenously in hospital settings.

The primary data supporting the EUA for Paxlovid is from EPIC-HR (Evaluation for Protease Inhibition), a randomised, double-blind, placebo-controlled clinical trial studying Paxlovid for the treatment of non-hospitalised symptomatic adults with a laboratory confirmed diagnosis of SARS-CoV-2 infection. Patients were 18 years of age and older with a prespecified risk factor for progression to severe disease or were 60 years and older regardless of prespecified chronic medical conditions. All patients had not received a COVID-19 vaccine and had not been previously infected with COVID-19. The patients who most benefited during the trial were those who'd begun treatment with the pills within three days.

Side effects

The approval comes with warnings of side effects. These include an impaired sense of taste, diarrhoea, high blood pressure and muscle aches. Using Paxlovid at the same time as certain other drugs could results in potentially significant drug interactions, according to the FDA. Using Paxlovid in people with uncontrolled or undiagnosed HIV-1 infection may lead to HIV-1 drug resistance. Ritonavir may cause liver damage, so caution needs to be exercised when giving Paxlovid to patients with pre-existing liver diseases, liver enzyme abnormalities or liver inflammation.

During the MOVE-OUT trial, side effects observed included diarrhoea, nausea and dizziness. The safety and effectiveness of Molnupiravir for the treatment of COVID-19 is still being evaluated according to the FDA.

Paxlovid is not recommended in patients with severe kidney or severe liver impairment. In patients with moderate renal impairment, a reduced Paxlovid dose is needed. Molnupiravir, the FDA warns, may cause foetal harm when administered to pregnant women. Therefore, Molnupiravir is not recommended for use during pregnancy.

No retail price for the drug has been announced. Pfizer has an agreement with the U.S. government for the purchase of 10 million treatment courses for $5.29 billion — which amounts to around $529 per treatment course making it unaffordable for a large part of the world. In early November, and ahead of the drug’s approval, the U.K. purchased 250,000 courses of Paxlovid and Pfizer has claimed an agreement with Israel for supply. The U.S. government has ordered three million doses of Molnupiravir which is expected to be delivered by January end. Each treatment course will reportedly cost $700. The U.K. Government has committed to purchase a total of 2.23 million courses of Molnupiravir.

Merck has entered into advance purchase and supply agreements for the drug with governments for over 30 countries worldwide, including Australia, Canada, South Korea, Japan and Thailand. The company claims that it has entered into agreements with manufacturers in several other countries and this may, therefore, mean lower prices. However, scaling and manufacturing of the medicine presents its own challenges and it could be months before the medicine is readily available in India. This is not accounting for the time regulatory authorities will take to clear it. The future course of the pandemic will determine demand for the drug.

‘Medical apartheid’

Several other medicines with antiviral properties have been explored earlier in the pandemic, including fapiravir and remdesivir. None have had a proven track record in reducing hospitalisation or saving lives. However, Paxlovid comes at a time when vaccines are widely available in several countries and it is these countries that are most likely to avail of the treatment when available.

Organisations such as the Medicins Sans Frontiers have said inequitable availability of the pill would whet ‘medical apartheid’.

“With patent applications still pending, countries should stand firm and refuse to grant any patents on nirmatrelvir/ritonavir, while generic companies should start preparing to produce the medicine without waiting for Pfizer's permission. If Pfizer is really interested in ensuring global access to this treatment, it should make clear that it will not stand in the way of generic production and competition anywhere, and refrain from imposing intellectual property barriers everywhere for the duration of pandemic,” Mihir Mankad, senior global health advocacy and policy adviser at MSF-USA, said in a statement.

0 / 0
Sign in to unlock member-only benefits!
  • Access 10 free stories every month
  • Save stories to read later
  • Access to comment on every story
  • Sign-up/manage your newsletter subscriptions with a single click
  • Get notified by email for early access to discounts & offers on our products
Sign in


Comments have to be in English, and in full sentences. They cannot be abusive or personal. Please abide by our community guidelines for posting your comments.

We have migrated to a new commenting platform. If you are already a registered user of The Hindu and logged in, you may continue to engage with our articles. If you do not have an account please register and login to post comments. Users can access their older comments by logging into their accounts on Vuukle.