The COVID-19 pandemic isn’t over yet. Despite the success of vaccines, people continue to get the disease. Most cases are in the unvaccinated, but even those who have been fully vaccinated can have “breakthrough” infections. Relief appears to be in sight. Two new antiviral drugs promise effective treatment in pill form. Well-designed randomized controlled clinical studies in recently infected patients who have risk factors have shown that both drugs greatly reduce the risk of serious disease and hospitalization.
It’s interesting that the new drugs were developed by Merck and Pfizer, the same companies that developed the most effective vaccines. Merck’s molnupiravir introduces mutations into the viral genome during viral replication. Could it cause mutations in human DNA? Would it be risky to use it during pregnancy? Pfizer’s Paxlovid works by inhibiting an enzyme the virus needs to replicate. Paxlovid is combined with another drug, ritonavir, to prevent the liver from breaking down the antiviral before it can act.
Molnupiravir (brand name Lagevrio) has already been approved in the United Kingdom only a month after it was shown to decrease the risk of hospitalization by half in patients with mild to moderate COVID-19 who had risk factors. It’s not yet available in the United States. Soon afterward, Pfizer announced that its antiviral pill Paxlovid cut the risk of hospitalization by even more, 89 percent. Other antiviral drugs that are used to treat the disease are expensive and must be given intravenously in the hospital. The new drugs are less expensive and could be taken at home. This could be a real game-changer. But it’s no magic bullet and implementing their use in the real world could be problematic.
While the results of the clinical trials sound impressive, they have yet to be peer-reviewed, and many questions remain. No deaths occurred in the trials, but there weren’t enough patients to determine whether the drugs could reduce the risk of death. Only minor side effects were observed in the trials, but we know from experience that serious side effects can emerge in a drug after approval, when more people take it and users don’t match the profile of subjects in the trials. We don’t yet know if the drugs reduce the risk of the patients transmitting the infection to others or if they can prevent infection if given to those who have been exposed. If an outbreak occurs in an area, would it be feasible to give the pills to vaccinated people to improve their immunity and prevent spread of variants?
Will the new pills work against all variants of COVID-19? Might they contribute to the development of new variants? Will drug resistance develop? What if treatments are combined? Will wealthy countries buy up the available stores, depriving those in other countries? Anti-vaxxers may use the availability of these pills as another excuse to avoid vaccination, but vaccination is still our best hope for ending the pandemic.
Treatment Regimen and Cost
In the studies, the pills were started within five days of documented infection. Four pills were taken twice daily for five days, for a total of forty pills. The United States has pre-ordered 1.7 million courses of treatment (pending approval) at a cost of $700 per patient treated. Both companies have asked for Emergency Use Authorization (EUA) in the United States.
Implementation May Be Problematic
Imagine this scenario: a patient develops symptoms they think might be due to COVID-19. They have difficulty arranging for a test, and when they finally get tested, they have to wait a couple of days to get the results. If the test is positive, they have to get an appointment with a doctor to get a prescription and then have to find a pharmacy that has the pills in stock. By the time they get the pills, more than five days have passed. Insurance may not pay.
For the new pills to be a practical option, people would have to be knowledgeable about the symptoms that suggest COVID-19 and would have to have easy access to an inexpensive, reliable at-home test (ideally, they would already have such a test at home ready to use). They would have to have swift access to a doctor who would prescribe the pills, and their local pharmacy would have to have a ready supply. If insurance didn’t cover it, they would have to be able to afford it. Would it be feasible for everyone to keep a supply at home in case they might need it at some future date?
Conclusion: Cautious Optimism Is Warranted; Stay Tuned
The development of pills to treat COVID-19 is really exciting, but it’s early days yet, too soon to start celebrating. There are too many unanswered questions that can only be addressed by further clinical trials. Early positive reports are all too often followed by negative ones; but if for some reason these two pills don’t pan out, we can hope that other, more effective ones will follow. Keep your fingers crossed and stay tuned!
This article was originally published as a SkepDoc’s Corner column on the CSI website.