January 12, 2022
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, the world needs 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, also has been authorized.
The best authorized treatment for COVID-19 has been an infusion of monoclonal antibodies, which UNC Health offers at several clinics. However, 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 years old who 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 this treatment, all of which should be available to the public by the end of January.
The federal government also has a contract in place to purchase 10 million courses of paxlovid, but Pfizer says it will have only about 265,000 treatment courses available by the end of January. Pfizer says it is ramping up production of paxlovid to manufacture more each month and reach 10 million total doses by late summer. Paxlovid will be available for adults and children ages 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, director of Emerging Pathogens at the UNC Institute for Global Health and Infectious Diseases and associate professor of pulmonology and critical care medicine at the UNC School of Medicine. “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. Researchers at the UNC Gillings School of Global Public Health 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, William R. Kenan, Jr. Distinguished Professor of epidemiology at the Gillings Schools and professor of microbiology and immunology at the UNC School of Medicine, is one of the world’s foremost coronavirus researchers. His lab’s experiments, led by Timothy Sheahan, PhD, first showed molnupiravir’s effectiveness in 2020.
The pill stopped the virus from multiplying. Fischer took notice.
Fischer and colleagues in the Institute for Global Health and Infectious Diseases worked with the drug company to ramp up clinical trials. At the same time, Baric and Gillings School 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 Fischer at the 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 of 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 has important implications for both preventing the progression to severe disease and potentially transmission,” 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 says 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 treatment 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%. 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, so comparing data results is not easy. Also, real-world efficacy often does not perfectly mirror clinical trial results. Still, each pill shows more promise based on gold standard randomized double-blind 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,” Fischer says. “This will be important if case resistance develops to one of them or if these medications are allowed for different patient populations.”
Contact the UNC Gillings School of Global Public Health communications team at firstname.lastname@example.org.