The monkeypox outbreak is a rapidly evolving international issue. Health experts are warning that the virus is changing at a fast pace, potentially leading to resistance to an antiviral medication used to treat patients at risk of severe illness.
The Food and Drug Administration (FDA) is urging caution in prescribing the drug tecovirimat, also known as TPOXX, due to its potential for immune resistance.
“Viruses can change over time. Sometimes these changes make antiviral drugs less effective at fighting the infection they are targeting, meaning those drugs may not work as well or may not work at all,” the FDA stated in guidance released online and as part of updated labeling for TPOXX.
The FDA’s new guidance added that TPOXX has a “low barrier to viral resistance” and even small changes to a monkeypox viral protein called VP37 could have a significant impact on the antiviral activity of TPOXX.
Here’s a closer look at what that means for the future of monkeypox and treating at-risk patients.
In its new guidance, the FDA explained that the antiviral drug TPOXX works by inhibiting the VP37 protein that orthopoxviruses like smallpox and monkeypox all have. Studies have identified several genetic pathways for orthopoxviruses to become resistant to tecovirimat or TPOXX, the FDA added.
Due to these concerns, “CDC researchers are actively monitoring for changes in the monkeypox virus that may make the virus less susceptible to TPOXX,” the FDA warning includes.
It takes just a “single anomaly” in a DNA sequence that codes for a specific amino acid for the virus to develop resistance to tecovirimat, Monica Gandhi, MD, MPH told Health.
“In layperson’s terms, this simply means it will not be that difficult for the monkeypox virus to develop resistance to tecovirimat, a process that will likely occur if we use tecovirimat broadly so the virus has ‘pressure’ to develop this resistance in order to still reproduce when tecovirimat is administered,” Dr. Gandhi added.
The major concern surrounding the FDA’s warning is that “tecovirimat resistance will develop rapidly, Eleftherios Mylonakis, MD, PhD the Charles C.J. Carpenter, MD professor of infectious diseases, professor of medicine, assistant dean of medicine, and professor of molecular microbiology and immunology at the Alpert Medical School of Brown University, told Health.
If that were to happen, it would have significant implications, Dr. Mylonakis said. Given that there are limited monkeypox vaccine supplies, the resistance risk posed by mutations is real and could even mean monkeypox is here to stay, said Dr. Mylonakis.
The FDA warning raises questions about who should and who should not receive TPOXX moving forward.
The FDA suggests that those who are not at risk for more severe illness– in other words, those who have a healthy immune system already– but may still contract monkeypox, should be cautious about taking TPOXX.