Unproven monkeypox drug: Out of storage, into bodies?
TPOXX is a medicine that we hoped never to use.
But the antiviral drug, created to save us from weaponized smallpox in a bioterrorism attack, now is a promising tool in civilian care: treating monkeypox, a virus that is infecting about 1,000 Americans every week.
Because it has not undergone official human testing and is not approved for the treatment of monkeypox, that shift has been a formidable challenge — causing delays, piles of paperwork and denial of care. And federal officials so far are resisting emergency measures that could provide it to suffering patients more quickly.
“I suffered for two weeks trying to convince Kaiser to let me have the treatment. The pain was absolutely crippling,” said Dominic Sardina, a 42-year-old San Francisco web designer and one of an estimated 1,310 Californians who have contracted the virus. Within several days of starting treatment, his symptoms improved, but he can't rule out that he would have healed on his own.
San Francisco attorney Stephan Ferris, a Kaiser patient, said he was only offered painkillers. “I called every day for about a week, and it was always the same answer: `We won't prescribe you TPOXX. We will prescribe you opiates for pain.' … They were rationing who got it and who didn't.”
The drug, also known as tecovirimat, is only available under the Food and Drug Administration's restricted “Investigational New Drug” protocol. The Biden administration's declaration of a public health emergency on Thursday stopped short of taking the steps needed to allow widespread distribution of the drug, the one potential treatment for the debilitating disease. So far, about 14,000 of 1.7 million available courses of treatment have been used.
The drug has only been approved for use against smallpox. So doctors who request its use in monkeypox care confront major regulatory paperwork. And they can't conveniently order it from a local pharmacy. Instead, it must be shipped from the federal government's Strategic National Stockpile.
Frustrated, doctors and patients are pushing for reforms that would ease access to TPOXX. They are urging the FDA to make it available through an emergency use authorization , a regulatory pathway that allows broader use of an unapproved drug to treat serious disease.
But federal officials have resisted a free-for-all, saying it is important to first collect crucial data about the drug's safety and efficacy.
On Tuesday, regulators announced a plan to conduct a human clinical trial. That will take time. Designed by the National Institutes of Health, it will be placebo-controlled and enroll about 500 patients. Such a trial was never possible until this major new outbreak provided the opportunity.
“It's never been tested in people with the disease,” said FDA commissioner Dr. Robert Califf. “We think it's got to be effective in monkeypox, but we have no proof of that yet.”
TPOXX was created to combat the unthinkable: a smallpox attack. While smallpox has been eliminated in the wild, frozen stocks of the virus are still maintained by the governments of the United States and Russia. Experts worry that rogue scientists or terrorists could get hold of the remaining supplies — or build their own virus.
Proactively, the Centers for Disease Control and Prevention stored TPOXX doses in a network of secret and strategically located repositories located throughout the U.S.
“Our drug was developed to be stockpiled,” SIGA Technologies CEO Dr. Philip Gomez said in an interview with Benzinga.com. SIGA, based in New York City, is the sole manufacturer of the medicine.
But the surprise appearance of monkeypox has created a surge in demand.
Doctors and advocates are now urging that TPOXX be pulled off the shelves and put into bodies.
“The U.S. is basically sitting on a pot of gold here,” according to Dr. Jay Varma, director of the Cornell Center for Pandemic Prevention and Response.
Federal regulators were willing to cut corners when approving its use against smallpox, a highly infectious disease with a 30% to 50% fatality rate. Because smallpox has been eradicated, they couldn't test it in people, and instead, tested it against a related virus in animals.
Monkeypox is different, say federal regulators. It's now possible to test the drug in humans. And animal data alone isn't good enough. In last week's New
England Journal of Medicine, experts with the FDA, CDC and National Institutes of Health urged more research and adherence to a drug review process that is widely regarded as the global gold standard.
Both smallpox and monkeypox are orthopoxviruses, and, in theory, the drug is almost certain to be helpful because the two pathogens are so closely related, said infectious disease specialist Dr. Daniel Shin of El Camino Hospital in Mountain View. Studies show that TPOXX cured monkeypox in animals. There are early unpublished reports that it helped patients, reducing disease severity and shortening the duration of symptoms. So far, there are no major side effects.
The drug's current system of distribution gathers important data — but comes with extra steps and paperwork. Only patients who meet specific criteria — such as young children, pregnant women, the immunocompromised and people with severe disease or lesions near the eye, urinary tract or anus — are eligible.
“This is not a medication that you call your doctor and just get it,” said Dr. Jorge Salinas, co-director of Stanford's Infection Prevention and Control Program. Stanford has a 12-person team to process TPOXX requests.
To get the drug, health care providers must first swab a patient to confirm infection. The doctor fills out, by hand, the CDC's four-page “patient intake form.” It requires the approval of a hospital's institutional review board. The patient then signs a form showing informed consent to take the drug. All that paperwork is faxed to the CDC for approval.
“If you have 15, 20 or 30 patients who need it, and qualify, physicians are just filling out forms all day,” Shin said. “This is not sustainable.”
The drug is then ordered from a government pharmacy, such as the San Francisco and Santa Clara County department of health. Those pharmacies, as well as Kaiser Permanente, obtain it from the California Department of Public Health, which is supplied by the federal government's Strategic National Stockpile.
Additional paperwork is needed after the patient's treatment, along with a follow-up visit. Patients may also voluntarily submit their own reports and photographs.
“I took three pills, twice a day, for two weeks,” isolating the whole time, said Sardina, who had developed a dangerous secondary bacterial infection and documented his recovery. “A day or two after starting, I finally started seeing a turnaround. I definitely believe it helped, but there's no way to know.”
Before he got TPOXX, Sardina said he was in so much pain, “I was pounding the ibuprofen and Tylenol, back and forth, for hours.”
If TPOXX was more readily available, it could be prescribed more promptly, helping patients who are in tremendous pain and perhaps slowing the spread of disease, said UC San Francisco infectious disease expert Dr. Peter Chin-Hong.
“In the world of infectious disease, treating a virus early is always better,” he said. “Right now, we're treating people who are in so much pain, and we want them to feel better.”