CDC, NIH, FDA leaders call for US-based clinical trial of smallpox drug in treating monkeypox
With the rising number of monkeypox cases, leading researchers at the CDC, FDA and NIH are calling on a randomized clinical trial to see if an approved smallpox drug is effective at treating monkeypox.
No monkeypox treatments are approved in the US, so patients looking to get relief for their lesions and other symptoms from the virus must go through a set of hurdles to get the smallpox drug through a government expanded access program. Approved for smallpox in 2018, the drug is marketed as TPOXX by the biotech SIGA. The European Union approved it for monkeypox in addition to smallpox earlier this year and the UK followed suit in July.
In an opinion piece published in the New England Journal of Medicine on Wednesday, government researchers said the NIH’s National Institute of Allergy and Infectious Diseases is working with the AIDS Clinical Trials Group, which has overseen studies of HIV meds since the 1980s, to set up a clinical trial to test TPOXX for monkeypox.
But while NIAID, ACTG and SIGA all confirmed to Endpoints News via email that a US-based clinical trial of the drug is being planned, they declined to say when it would start. Activists argue the trial should have taken place before monkeypox became a global outbreak because the virus has been endemic in some countries in Africa for years.
“Adults with monkeypox infection, including people living with HIV, would be eligible to enroll. NIAID will share more information as it becomes available,” the NIAID said in an emailed statement.
“Those trials should have been obviously planned for well before a current outbreak. This is what the job of pandemic preparedness is. We obviously had millions of doses stockpiled for this purpose and it is insane that the federal government didn’t actually have efficacy trials planned for it,” James Krellenstein, strategy & policy managing director for the organization PrEP4All, told Endpoints in a phone interview.
The researchers analogize the lack of approved meds for the current monkeypox outbreak to the early years of the HIV epidemic in the 1980s, when therapies had been developed, but the process for approving their use in humans was “painfully slow.” An ethical balance was needed to ensure patients had access while also “upholding the responsibility” of ensuring they were safe and effective, the researchers wrote Wednesday in NEJM.
“Now, 34 years later, we are faced with an uncannily similar situation,” they wrote. The authors of the piece include John Brooks, CMO for the CDC’s Division of HIV Prevention; Debra Birnkrant, director of the Division of Antivirals within the FDA’s Center for Drug Evaluation and Research; and Peter Kim, deputy director of the Therapeutic Research Program in the Division of AIDS at NIAID.
Organizations such as PrEP4All have called for the removal of restrictions to the drug so patients can get the med quicker and more easily as monkeypox case counts climb past 25,000 across 83 countries. The US is one of the biggest outbreak regions and three states — Illinois, New York and California — have declared it a public health emergency.
Prior to the current global outbreak, the NIH had begun planning for a randomized clinical trial of the drug in the Democratic Republic of the Congo, but in their NEJM piece, the researchers cite the need for a US-based trial since current worldwide cases are of a different clade than what is seen in the DRC.
The US has access to about 1.7 million courses of the drug through the Strategic National Stockpile, and BARDA has a contract with SIGA to replenish the courses when they expire, according to the company. As of last week, 10,000 courses of the drug had been sent to states and cities upon request, the Department of Health and Human Services told NPR.
A SIGA spokesperson said the company is “aware of the plans for a clinical trial and is working with NIIAD [sic] to advance a placebo-controlled study of tecovirimat in the treatment of monkeypox.” SIGA reports quarterly earnings on Thursday.
SIGA canceled a scheduled interview between science chief Dennis Hruby, CEO Phillip Gomez and Endpoints, saying that it “would prefer to wait for publication of the full article in NEJM before commenting much further on any specifics.”
Hruby told NBC News last month that plans for large clinical trials were in advanced stages in Canada, the UK and the EU. Hruby told the news outlet that SIGA might not rely on US trial data to submit to the FDA, but rather look to combined findings in other countries and safety data from global compassionate-use programs.
In their NEJM piece, the CDC, FDA and NIH researchers wrote that they “anticipate that these trials will provide data needed for clinical and regulatory decision making in the United States.”
SIGA’s drug was approved in the US in 2018 under the “Animal Rule,” which allows drugs for serious or life-threatening conditions to be greenlit when human studies are deemed unethical. Efficacy is established in animal models of the human disease. The drug was approved based on efficacy data gathered from infecting nonhuman primates with monkeypox virus and rabbits with rabbitpox virus, as well as safety data from more than 400 healthy adult volunteers.
As the monkeypox outbreak spreads to more than 6,000 reported cases in the US, people at highest risk have been scrambling to get vaccinated against the virus. There is one jab approved in the US, Bavarian Nordic’s Jynneos, which is in limited supplies in the US after a national stockpile largely evaporated in recent years. A smallpox vaccine, ACAM2000, is also being used in certain instances.
Meanwhile, Moderna leaders said Wednesday that the pandemic-infamous biotech is looking into a potential monkeypox program.