Monkeypox patients should not be left to suffer when an FDA-approved drug could help

Andy couldn’t sleep more than a couple fitful hours a night because it felt like a hot fork was stabbing him in the butt. He had excruciating internal and external lesions around his anus. It was the weekend: his doctor wasn’t available, an emergency department provider told him he might have anal cancer, and an urgent care provider sent him home with Tylenol and no diagnosis.

Andy (not his real name) texted one of us. We knew he almost certainly needed to be tested for monkeypox. It took seven days for him to get a test and, when the results came back from the New York City Health Department five days later, he learned he tested positive for monkeypox. Then came the next challenge: getting Andy a prescription for tecovirimat (brand name TPOXX), an FDA-approved drug developed and stockpiled by the U.S. government that may reduce symptoms and risk of death in patients with monkeypox.

Currently, most people with monkeypox have no access to this drug, and few providers are even aware it is available. Members of the gay community have been messaging each other to try to find it and are growing increasingly angry that they cannot access the one drug that could ease the suffering of people with monkeypox, not to mention their limited access to testing or vaccines.

We believe there is an urgent need for the federal government to simultaneously align two public health objectives: make it easier for people with monkeypox to get tecovirimat and collect high-quality data on its effectiveness.

It is important to understand the history of tecovirimat, because it represents the impressive success of U.S. government pandemic preparedness and its simultaneous failure at pandemic response.

After the anthrax bioterrorism attacks in 2001, federal officials became increasingly concerned about the risk of someone attacking the U.S. military or general population with smallpox virus. Smallpox is a highly transmissible and lethal viral infection that was declared eradicated in 1980, but it could be re-introduced by unaccounted for stocks of the virus or new synthesis in a laboratory.

An intensive 17-year collaboration between U.S. health and defense agencies — including the National Institutes of Health, the Centers for Disease Control and Prevention, the Food and Drug Administration, and the U.S. Army Medical Research Institute of Infectious Diseases — led to a drug that blocks the smallpox virus and related viruses like monkeypox from replicating; proved its effectiveness in two different animal models; and documented its safety in a clinical trial of 431 healthy human volunteers.

In 2017, the FDA approved tecovirimat for treating smallpox using a special regulatory pathway developed between 2002 and 2015 known as the “animal rule.” It allows the FDA to approve a drug for treating a disease in humans based on placebo-controlled studies in animals if such trials cannot be conducted in humans because the disease is rare or a clinical trial would be unethical.

FDA’s approval came with a unique stipulation: it could be sold only to the federal government’s Strategic National Stockpile, a program run by the U.S. Department of Health and Human Services. The stockpile maintains large supplies of drugs, ventilators, vaccines, and other medical supplies in case of a public health emergency like a natural disaster or bioterrorism attack. To date, HHS has made the judgment that it should be the CDC’s decision about who can prescribe tecovirimat and how it can be used.

The CDC has decided that, because the FDA initially approved the drug only for treating smallpox, it requires every patient receiving tecovirimat for monkeypox to enroll in a clinical study. The trial requirements are highly labor intensive for patients and providers, involving in-person office visits, photographs of lesions, and detailed paperwork. The investigative new drug protocol for tecovirimat’s use is 124 pages long and requires multiple institutional authorizations including, in most academic centers, a review by the center’s research ethics committee.

In a nutshell, that means only highly specialized medical centers, such as those affiliated with universities, are likely to enroll and treat monkeypox patients with tecovirimat. This leaves patients outside of major cities — or those who distrust medical research or choose not to participate in it — without access to treatment, potentially mirroring the disastrous HIV epidemic in rural America.

More than one million doses of tecovirimat are currently sitting in the National Strategic Stockpile, with only a few doses having been released to health departments for use, even as monkeypox cases continue to rise.

At the time of Andy’s diagnosis, only one doctor at one large academic medical center in New York could prescribe the drug. Not long afterward, a second large academic medical center — Weill Cornell Medicine, where one of us (J.V.) works — also began enrolling patients. Two days later, Andy visited a physician at Weill Cornell, had pictures of his lesions taken, and went home with a two-week supply of tecovirimat. Within 24 hours, his pain abated. Within six days, his lesions were entirely healed. The next day, his doctor gave him the go-ahead to stop isolating.

To be sure, this is an anecdotal case. But it supported by observational clinical studies showing that tecovirimat decreases the duration of monkeypox symptoms.

A San Francisco man with monkeypox contacted us via social media. Before becoming infected, he had a skin condition that could lead to higher risk of developing a severe case of monkeypox, and should have access to tecovirimat based on CDC guidance. Plus he lived in a large city with multiple academic medical centers, yet he couldn’t find anyone to prescribe the drug.

Most people with monkeypox that we know are being told they simply have to manage their symptoms and treat their pain with over-the-counter pain medications.

We believe that the CDC and FDA should take immediate steps to expand access to tecovirimat for people with monkeypox.

First, the FDA could expand its approval of tecovirimat to include treatment of monkeypox. Even though the FDA approved the drug only for smallpox, the basis for that approval was a clinical trial in monkeys with monkeypox, showing a marked reduction in skin lesions and death. Notably, tecovirimat is approved in the European Union for treatment of both monkeypox and smallpox.

Second, the CDC could continue to enroll patients in a trial when they present to large academic medical centers but allow treatment by providers in rural areas, private clinics, or other facilities to prescribe tecovirimat initially off-label for immediate use without FDA authorization, getting around the time and staffing needed to conduct a trial. Telehealth could play a vital role in getting patients the treatment they need and even for collecting data on lesion number and duration without requiring patients to travel to the provider and break isolation.

One argument against expanded access is that tecovirimat was approved because smallpox is highly lethal, whereas — at least in this outbreak — monkeypox has not killed anyone in North America. We contend that lethality should not be the only consideration. People with monkeypox describe symptoms that are certainly not “mild.” Andy’s case, and others who have come forward to describe their monkeypox symptoms on social media, demonstrate that the infection can be incredibly painful. The monkeypox lesions themselves can be internal, in the rectum, or on sensitive body parts like in the groin, on the face, on the penis, in the mouth and throat, or on the scalp. In many people, these lesions are painful and at risk of getting infected, leading to skin infections and abscesses that require further treatment. In fact, up to 10% of monkeypox patients in the U.K. have required hospitalization, though this includes some people who were admitted because they were unable to isolate at home.

Second, people with monkeypox are told to isolate from social and sexual contact until their lesions heal entirely and a fresh layer of skin has formed, which can take up to six weeks. As Covid-19 has demonstrated, many patients find it financially, logistically, and emotionally impossible to isolate for even a week. In one study, nearly half of Covid-19 patients didn’t properly isolate for the 10-day period; isolation for monkeypox is likely twice as long at least. Long recommended or mandatory isolation periods imposed by public health agencies may also disincentivize people to get tested for monkeypox. If tecovirimat can accelerate time to recovery, patients are more likely to isolate fully, leading to less onward spread of the virus.

Third, expanding the ability of clinicians to prescribe tecovirimat could provide data about another possible benefit of tecovirimat, such as treatment of people exposed to monkeypox but not yet sick with it (akin to post-exposure prophylaxis for HIV). The biology of tecovirimat strongly suggests that people could benefit by taking the drug after exposure but before they are sick as a way to prevent or diminish the occurrence of disease.

With HIV, cancer, and other severe diseases, there has long been a tension between studying safety and efficacy in controlled trials and ensuring access to those living with a disease right now. With this monkeypox emergency, the U.S. is incredibly lucky to have FDA-approved tests, treatments, and vaccines to diagnose the virus, prevent its spread, and limit the suffering of those already ill. The federal government’s development, evaluation, and purchase of tecovirimat should be lauded as an example of the importance of investing in pandemic preparedness. But the government’s failure to actually use the fruits of that success to control this outbreak must change.

People with monkeypox must not be left to suffer in pain while an approved drug sits on the shelf unused.

Jay K. Varma is an infectious disease physician and epidemiologist, a professor of population health sciences at Weill Cornell Medicine, and director of its Center for Pandemic Prevention and Response. Joe Osmundson is a virologist at New York University, a gay health activist, and author of “Virology: Essays for the Living, the Dead, and the Small Things in Between” ‎ (W. W. Norton & Company, June 2022).