The Pills to Fight COVID-19

There are new weapons in the war against COVID-19: antiviral pills that you take once you’ve been infected to fight the virus before it multiplies and causes major damage.

Vaccines are powerful in preventing serious illness and death from COVID-19, including from the omicron variant. But to save as many lives as possible, we need other prevention strategies and effective treatments. The FDA recently authorized one, a pill called molnupiravir, developed by Ridgeback Biotherapeutics and Merck. A second antiviral pill from Pfizer called paxlovid has also been authorized.

For several months, the best authorized treatment for COVID-19 is an infusion of monoclonal antibodies, which UNC Health offers at several clinics. But monoclonal antibody treatments are logistically complicated to deliver and not universally available. At the peak of the pandemic, clinics were fully scheduled, which worked against the goal of treating people as quickly as possible.  Now, because of the  omicron variant, the two top monoclonal cocktail therapies are not proving effective. A third monoclonal treatment called Sotrovimab is effective, but large supplies are not yet available and won’t be for several weeks.

With the Merck antiviral pill, patients over 18 at high risk of severe disease and hospitalization would get a prescription filled at a local pharmacy immediately after they test positive for COVID-19. Patients take four pills twice a day for five days. The federal government has agreed to purchase 3 million courses of treatment, all of which should be available by the end of January 2022.

The federal government also has a contract in place to purchase 10 million courses of paxlovid treatment, but Pfizer says it will have about 265,000 treatment courses available by the end of January. Pfizer says it is ramping up production of paxlovid to produce more each month and reach 10 million total doses by late summer 2022.  Paxlovid will be available for adults and children age 12 and older who weigh at least 88 pounds and who are at high risk of severe disease and hospitalization.

“The oral delivery of these treatments gets around the logistical challenges of infusion based therapies, and that’s critical as it will allow increased access to treatment.” says William Fischer, MD, UNC Health pulmonary and critical care doctor. “A global pandemic requires global solutions – so the response to the COVID-19 pandemic requires that we figure out how to get safe and effective vaccines and treatments to people who need them. Incorporating the consideration of access into our response strategy is the only way we can slow the spread of this pathogen.”

Developing COVID-19 Antiviral Pills

Emory University scientists created molnupiravir several years ago as a potential flu treatment and called on UNC researchers to test it against several viruses, including coronaviruses, with the hope of creating a medication before the next viral outbreak and potential pandemic. This UNC-led research began in 2016 and showed that the drug alters the virus’s genetic code, making it much harder for the virus to multiply and cause severe disease. They demonstrated that molnupiravir was effective against various types of coronaviruses.

When the COVID-19 virus spread around the world in early 2020, UNC-Chapel Hill researchers immediately began testing molnupiravir’s safety and efficacy against the particular coronavirus called SARS-CoV-2, which causes COVID-19.

Ralph Baric, PhD, Kenan Distinguished Professor of Epidemiology and Microbiology & Immunology, is one of the world’s foremost coronavirus researchers. His lab’s experiments, led by Tim Sheahan, PhD, first showed molnupiravir’s effectiveness in 2020. The pill stopped the virus from multiplying. Dr. Fischer took notice.

Fischer and colleagues in the Institute for Global Health and Infectious Disease worked with the drug company to ramp up clinical trials. At the same time, Baric at the UNC Gillings School of Global Public Health and Gillings assistant professor, Lisa Gralinski, PhD, teamed up with UNC School of Medicine researchers Victor Garcia, PhD, and Angela Wahl, PhD, to conduct in-depth research on exactly how the drug killed the virus in human tissue without harming human cells.

Clinical trial results showed that molnupiravir reduced hospitalizations and deaths significantly in people recently infected with SARS-CoV-2. Both phase 2 and 3 trials, one of them led by Dr. Fischer at UNC Medical Center, revealed that patients who took the drug at their first sign of COVID-19 symptoms had a quicker reduction in virus levels than those in a placebo group. After five days, tests were unable to detect infectious virus in volunteers who took 800mg molnupiravir twice a day. The percentage of patients with adverse effects was similar in each group, whether patients received the drug or the placebo.

“The reduction in infectious virus in the nose of individuals who received molnupiravir have important implications for both preventing the progression to severe disease and potentially transmission,” Dr. Fischer says. “This is a key complement to our current vaccines and monoclonal antibody treatments because it allows us to treat people as early as possible which is critical to stopping the virus.”

Fischer adds it’s important to note that 14% of people in the placebo arm of the study were hospitalized and/or died.

New Hope for COVID-19 Treatments

Pfizer’s paxlovid blocks the production of a viral enzyme that the coronavirus needs to multiply. It’s the same method used in HIV and hepatitis C drugs.

Pfizer released data in early November 2021 showing that the drug reduced hospitalization and risk of death by 89 percent. About 7% of patients in the placebo arm were hospitalized and/or died. The company says the occurrence of side effects was similar between patients who received the drug and those who received the placebo.

The Ridgeback/Merck and Pfizer pills followed different clinical trial parameters, and so comparing data results is not easy. Also, real-world efficacy often does not perfectly mirror clinical trial results. But each pill shows more promise based on gold standard randomized double-blinded clinical trials for antiviral effects than any treatment to date, aside from monoclonal antibodies.

“What’s really exciting is that we now have potentially two oral therapies that work differently to fight against this virus,” Dr. Fischer says. “This will be important in case resistance develops to one of them or if these medications are allowed for different patient populations.”


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