Monkeypox, which federal officials declared a public health emergency on August 4, is not as contagious as the other ongoing public health emergency in the U.S.: COVID-19. Monkeypox primarily spreads through contact with infected skin lesions. Theoretically, containing monkeypox should therefore be more feasible, as long as testing, vaccines, and treatments are accessible. But in reality, the rollouts of all three approaches have faced major challenges. Getting the antiviral drug tecovirimat, also known as TPOXX, is particularly difficult.
Here’s what to know about the antiviral drug treatment TPOXX.
What is TPOXX?
TPOXX is approved by the U.S. Food and Drug Administration (FDA) to treat smallpox, which belongs to the same family of orthopox viruses as monkeypox. It likely helps people with monkeypox as well.
TPOXX was approved for smallpox under a special regulatory process called the Animal Rule, which allows the FDA to approve a drug without first testing it in people. Because smallpox is such a dangerous and highly contagious virus, and is eradicated from the world, it wasn’t possible to test the drug in people and was instead tested in animals. Even in animals, researchers used not the variola smallpox virus but the related monkeypox virus as a stand-in, since only two labs in the world—one at the U.S. Centers for Disease Control and Prevention, and one in Russia—have samples of the smallpox virus and can conduct studies on that virus.
How do you get TPOXX?
Because it is not specifically approved for monkeypox, it cannot be prescribed and stocked at pharmacies. It is only distributed by the Strategic National Stockpile, the emergency stash of medications maintained by the federal government for public health emergencies.
The CDC has made TPOXX available under a compassionate use protocol. That requires any doctor interested in giving patients the medication to register and agree to the conditions of receiving the drug, and to ask their patients to sign informed consent forms acknowledging that they understand the drug has not been studied or approved for treating their condition. The process for providers is time-consuming, since doctors must agree to provide information about their patients’ symptoms and justify why they qualify for the drug.
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But because of the high demand, the CDC recently streamlined the paperwork down to the bare minimum requirements, says Dr. John Brooks, who heads the epidemiology research team in CDC’s division of HIV-AIDS Prevention. Once the CDC receives the doctor’s request, the order for the drug is sent to the Stockpile, and TPOXX is sent directly to the doctor within 24 hours.
Since 2013, SIGA Technologies—the pharmaceutical company that makes TPOXX—has provided 1.7 million doses of the drug for the stockpile, says the company’s CEO Phillip Gomez. Each dose remains potent for about seven years, so beginning in 2020, SIGA provided about 363,000 doses to replace those that have expired. The company has partnered with four manufacturing facilities to maintain the stockpile, and Gomez says SIGA is discussing with government health authorities about whether additional capacity is needed.
How effective is TPOXX?
The data on TPOXX in animals essentially reflect how well the drug works against monkeypox, but efficacy in humans is still unknown. In those studies, researchers gave non-human primates and rabbits lethal doses of monkeypox. More than 90% of those treated with TPOXX survived, compared to only one in 20 non-human primates treated with the placebo.
Dennis Hruby, chief scientific officer of SIGA Technologies says that anecdotal reports from patients treated with TPOXX suggest that the drug can reduce symptoms such as fever and fatigue and reduce the severity and pain associated with lesions. A course of TPOXX involves taking pills twice a day for 14 days.
How TPOXX works
Once the monkeypox virus is inside a healthy cell, the virus copies its genetic information and forms several membranes, or coverings, that allow it to burst out of the cell and circulate throughout the body to infect other cells. TPOXX works by preventing the virus from generating more copies of itself once it infects a host. It does this by blocking the formation of a secondary membrane, and traps the virus inside the cell. The body’s immune cells, including antibodies and T cells, then eliminate these virus-filled cells.
The earlier after infection TPOXX is used, the better it can prevent the virus from infecting other cells and causing more serious disease.
Can patients get TPOXX more quickly?
Hospitals in some hotspots have expedited access to TPOXX. In New York City, the department of health has obtained a supply of the drug from the Strategic National Stockpile and allowed select pharmacies—including the specialized pharmacy at Columbia University, which has a relatively high volume of monkeypox patients—to stock and dispense the drug. Dr. Jason Zucker, assistant professor of medicine at Columbia, says his team has prescribed the drug to just under 90 people. Doctors file a request describing the patient’s condition to the city health department, which reports the cases to the CDC and allows the doctors to release the drug to the patients.
That may seem tedious for patients and doctors, but it’s a necessary process given how little is known about how safe and effective the drug is for treating monkeypox. “It’s a drug that we have extremely limited data on, and we don’t actually know if it works,” says Zucker. “So this process is important.”
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In Los Angeles, county health officials have also obtained a supply of TPOXX from the National Stockpile and distributed it to certain hospitals and clinics, including University of California Los Angeles David Geffen School of Medicine. UCLA stocks a supply of the drug in its specialized investigational drug pharmacy, which only carries drugs like TPOXX that have not been fully approved and required additional regulatory steps and consent to dispense. Dr. Tara Vijaya, medical director of antimicrobial stewardship at UCLA, oversees distribution of TPOXX at UCLA Health and says so far, they health system has only provided the drug to under 10 patients. UCLA requires infectious disease doctors to discuss with patients the fact that TPOXX has not been fully studied to show that it is effective in treating monkeypox, and obtain informed consent from patients before prescribing the drug.
Because the hospital stocks the medication, patients could receive it while they are visiting the doctor directly from the hospital’s pharmacy, or have it sent to their home within 24 hours. Even with this system, however, doctors must fill out the appropriate forms from the CDC logging each patient who takes the drug.
For the most efficient access to the medication, Brooks of the CDC recommends that patients ask their doctors to register for compassionate use of TPOXX, or consult their local public health department for doctors who have already signed up and can receive the drug more quickly.
Will TPOXX be approved for monkeypox?
The FDA and CDC are looking for completed studies of TPOXX in people with monkeypox before expanding the drug’s current approval to include monkeypox. Even before the current outbreak, the National Institute of Allergy and Infectious Diseases, a branch of the National Institutes of Health (NIH), started a study of the drug among people infected with monkeypox in the Democratic Republic of Congo.
Because of the outbreak, the AIDS Clinical Trials Group, operated by the NIH, is also launching a new study of monkeypox patients in the U.S. to better understand how effective the drug is in controlling symptoms, and also how it affects patients if given together with the monkeypox vaccine. Based on animal studies that SIGA has performed, Hruby says that the drug does not appear to interfere with the process of developing immunity among people who have been vaccinated with either of the monkeypox vaccines: Jynneos or ACAM2000. The company had already begun studying healthy people who have been both vaccinated and then given TPOXX to determine if the combination is safe; the data will also help researchers to better understand how the immune system reacts to both the drug and vaccine if they are given together.
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Contributor: Alice Park