The U.S. Food and Drug Administration has not approved tecovirimat — sold under the brand name Tpoxx — specifically for use against monkeypox, but the U.S. Centers for Disease Control and Prevention has made the drug available from the Strategic National Stockpile by expanding access in the process. The global outbreak that has caused about 5,800 probable or confirmed cases in the United States.
Tpoxx was approved by the FDA in 2018 as the first drug to treat smallpox, a virus in the same family as monkeypox. The World Health Organization declared smallpox eradicated in 1980, but fears that the virus could be used as a weapon led the US government to stockpile more than 1.7 million courses of the drug in the event of a bioterrorist event. Tpoxx is approved in the European Union for the treatment of monkeypox as well as smallpox.
It can be taken intravenously or more commonly as a pill to be taken by mouth.
Tpoxx is considered experimental when it comes to treating monkeypox because there are no data to prove that it is effective against the disease in humans. Its safety was evaluated in healthy humans prior to the US Food and Drug Administration’s approval of smallpox, and its efficacy was tested in animals infected with smallpox-related viruses, including monkeypox.
As the ongoing outbreak increases demand for the drug, the Food and Drug Administration and the CDC recently relaxed some of the administrative requirements that health care providers face when requesting access.
However, doctors across the country point out that significant barriers remain, causing some patients to wait days for shipment or to travel to find medical centers that can supply the product at all.
“Patients are trying very hard to get this drug, even out of town or out of state in some cases,” said Dr. Peter Chen Hong, an infectious disease physician at UCSF Health. His hospital has received calls from patients across California as well as from Colorado and even Canada and the United Kingdom, all hoping to get treatment.
Health agencies are cutting routine, but challenges remain
The CDC says that doctors may want to use Tpoxx for people with symptoms of monkeypox in particularly dangerous areas such as the eyes, mouth, genitals, or anus. It may also be used in people with severe symptoms such as sepsis or encephalitis, or in people at risk of serious illness, including those with weakened immune systems due to conditions such as HIV/AIDS, and those with Skin diseases such as eczema, children, pregnant women and people with other complications such as bacterial skin infection.
Many people who contracted the disease during the outbreak experienced mild symptoms and recovered without treatment, but some doctors say they have seen more severely ill patients than they expected.
Dr. Mary Foote, medical director of the New York City Department of Health and Mental Health, said in late July that about 20% to 25% of patients there met the Tpoxx criteria. As of July 23, treatment has been prescribed for about 215 of the 839 confirmed cases.
“Anecdotally, among the providers we spoke to, we saw, very commonly, significant improvements within only a few days of onset and improvements in pain. Importantly, we saw no adverse events reported with few mild adverse events.” Some headaches, nausea. But that’s pretty much it,” Foote said.
However, it is not clear what proportion of the more than 5,000 probable or confirmed cases have been treated with Tpoxx. More than 223 people have been treated as of July 22, CDC officials said in a webinar, but the agency has not responded to requests for a more specific number.
Experts say the number of those treated may be a fraction of what qualifies.
“I think the majority of patients don’t have access,” said Chen Hong. He saw firsthand how difficult it was to get medicine.
Chen Hong treated Kevin Kwong, 34, after he developed painful lesions all over his hands, feet and face extending to his back, thighs and scalp.
“There were moments when I could barely swallow food because of the sores in the back of my throat,” Kwong said. Threatening pests near his eye for long-term effects on his eyesight.
But after his symptoms started, it took Kwong about five days to get to a facility where he could get Tpoxx. He spent four days telehealth visits and going to urgent care and emergency rooms where the rash worsened before doctors finally suspected monkeypox — and even then, he says, they didn’t know how to treat it and sent him home.
But his symptoms worsened, and he returned to the emergency room before he was advised to go to UCSF Medical Center because he was treating monkeypox patients. Tired and frustrated, he agreed to it out of desperation. Arrived there in the middle of the night. Several hours later, he met Chin-Hong and took his first dose of Tpoxx.
“He had to come forward and get to a county with Tpoxx and go to the emergency room of the hospital he knows might give him treatment because the place he came from doesn’t have treatment,” said Chen Hong. “If he doesn’t defend himself, he will never get Tpoxx.”
To obtain Tpoxx, a patient must sign a consent form from the CDC, and physicians must request access from the CDC or their local health department, which includes submitting things like lab tests and consent forms. The CDC and the U.S. Food and Drug Administration recently reduced the amount of paperwork required, made some testing and photo requirements optional, and allowed health care workers to begin treatment before the paperwork was submitted.
“They made it easier, but it still required more time, efforts and resources to be able to prescribe it,” said Dr. Jason Zucker, an infectious disease specialist at Columbia University Irving Medical Center.
Aside from the papers, Chen Hong says, there is a high “activation energy” that clinics and hospitals experience because the drug is considered experimental for monkeypox, and some hospitals and institutions require additional reviews of such treatments. As a result, Tpoxx has been disproportionately used in larger academic medical centers that have better infrastructure to work through these processes.
“We have this interesting situation – and it was in Covid as well – where the county without Tpoxx will negotiate with another county and the hospital to take the patient if he’s still sick and needs Tpoxx. So we might get another patient like that from another county in East. Bye today.” Chen Hong said of UCSF Medical Center.
A Pennsylvania man named Adam says it also took several days to get to Tpoxx.
“I would like to sort of liken it to a Covid hybrid, strep throat, mono, sort of all of those things together is the feeling of monkeypox, plus smallpox, which was a definite experience,” he said.
His doctors were concerned that a single lesion under his eyelash could affect his vision.
“He had a lesion on the inside of his eyelid, but if that ruptured, he would spontaneously pollinate his eye and could develop keratitis,” said Dr. Stacey Lynn of Central Wellness Center in Pittsburgh, who treated Adam. She was worried that it might put him at risk of blindness.
“By the time I was first seen and talked about the eyeball, the antivirals weren’t put in until about a week later,” Adam said.
In Adam’s case, his doctor’s office did not have Tpoxx, and after placing the order, it took four days to get there from the distribution center.
It usually takes two days after a doctor orders Tpoxx to reach a health care provider, the Pennsylvania Department of Health said in an email, since the CDC must first deliver the product to local public health locations.
“There are different operations in different states and in different hospitals. Each district or district will have its own problem,” said Dr. Aaron Glatt, chief of infectious diseases at Mount Sinai South Nassau in New York. “If you’re a private doctor or your clinic can’t get to the Tpoxx right away, they might ship it from national inventory, and you have to have a whole process — you know, the instructions, the shipping itself takes time, the paperwork filling out — that can take two days.
“In New York City, you can prescribe e-pharmacies with some pharmacies that will be able to make sure you fill out the right paperwork to go and have it delivered much faster,” he said.
How clinical trials can help
The safety of Tpoxx was evaluated by a study of 359 healthy people before it received FDA approval. Since smallpox has been eradicated since 1980, the drug’s benefits have been evaluated through experiments in animals infected with related viruses including monkeypox virus. There are no human trial data to prove its effectiveness in treating monkeypox.
“Anytime we use a new drug, it’s important that we do randomized controlled trials because it’s really the only way to know if it works,” Zucker said. Randomized controlled trials are studies that evaluate how effective a drug is in a group of people who get the drug compared to a group of people who don’t.
Zucker said he wasn’t sure if such trials would be ethical in people eligible for Tpoxx, because some participants would receive a useless placebo instead.
Dr. Jay Varma, professor of population health sciences at Weill Cornell Medical College, believes that such trials are ethical in mild cases, people who have been or are at risk of exposure, children and pregnant women.
“There is a need to obtain high-quality data on the risks and benefits of Tpoxx,” Varma said.
Not only will the experiments help generate much-needed data on how to use Tpoxx, Zucker said, they will help expand access in two ways. First, clinical data could help the drug qualify for a different type of regulatory approval that allows broader access with fewer obstacles. Second, the trials could help facilitate access for people who do not qualify under the current EAP, such as those with milder disease.
“Historically, antivirals are better earlier than they are later, but we have to prove that,” Zucker said, adding that plans are underway to conduct a US trial against monkeypox on Tpoxx.
Pharma compares the challenges of limited access and clinical data with the early days of the Covid-19 pandemic.
“The unfortunate parallel is that the United States is behind the United Kingdom and Europe in conducting these tests,” he said.
Lynn said she hopes the CDC and public health departments will continue to work toward improving access to the drug. But her expectations are measured.
“Until the FDA approves this for monkeypox or the national stockpile releases the stock for more normal distribution, that’s where we get,” she said.