US May Add ‘Toxic’ Antiviral Drug to Arsenal as Monkeypox Spreads

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(Bloomberg) — Struggling to contain the monkeypox outbreak that’s resulted in 1,000 US cases, US health officials may open access to an antiviral drug that has been little-studied in humans and comes with a risk of dangerous side effects. 

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The US Centers for Disease Control and Prevention is pursuing an expanded access protocol for Chimerix Inc.’s smallpox drug Tembexa to treat monkeypox, according to documents from an agency meeting in late June. An expanded access protocol would let clinicians use the drug as a back-up in some patients who don’t respond to other treatments.

Even as the number of cases grows and experts warn that the disease may prove hard to stamp out in the US, the Biden administration has touted US preparedness for monkeypox in part because of years of work guarding against an outbreak of smallpox, which is caused by a related virus. However, testing bottlenecks and strains on vaccine supply have emerged as threats to the White House’s handle on the contagion.  

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Tembexa won approval from the US Food and Drug Administration to treat smallpox in June 2021 under a rule used to greenlight drugs when they can’t be studied in humans. Because smallpox was eradicated in the 1980s, Tembexa’s effectiveness was instead assessed using rabbits and mice. Its safety profile was gleaned from use in non-smallpox patients who had contracted viral infections from stem cell transplants, during which some patients had to stop using the drug due to side effects. 

The medicine comes with a black-box warning on its label, indicating that it carries an increased risk of death when used for longer than its approved treatment course of two weeks. It can also cause diarrhea, nausea, vomiting, and abdominal pain. In data cited by the FDA, about 4% of patients stopped use of the drug because of its adverse effects.

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“For a drug that is particularly toxic, like this one, I’m not convinced that the benefits outweigh the risks,” said Luciana Borio, the former director of medical and biodefense preparedness at the US National Security Council.   

Tembexa is also linked to gastrointestinal issues and liver impairment, and may cause infertility. The CDC is seeking permission to use it through a regulatory process meant to widen treatment options for patients suffering from serious or life-threatening conditions. In May, Chimerix agreed to sell Tembexa to Emergent BioSolutions Inc., but that deal has not yet closed.

Another Option

Though the mortality rate during this monkeypox outbreak has so far been extremely low — the US has not reported any deaths — many patients are experiencing intense distress and discomfort from their symptoms, clinicians have said. Some may have permanent scarring from the lesions the virus causes, said Mary Foote, an infectious disease specialist from New York City’s Department of Health and Mental Hygiene. 

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Foote said that she estimates 20% to 25% of patients need antiviral treatment to help alleviate symptoms. So far, 70 of those patients have been prescribed Siga Technologies Inc.’s smallpox drug, known as Tpoxx, which the US has 1.7 million doses of in the Strategic National Stockpile. The drug can be prescribed for monkeypox under an expanded access protocol.   

CDC spokesperson Kristen Nordlund said in an email that the US hasn’t yet used Tembexa to treat monkeypox patients during this outbreak, but that pending the drug’s availability in the US stockpile, it could be prescribed for severe cases that don’t respond to Tpoxx.  

Data on the drug’s effectiveness in monkeypox is limited. A recent study published in the Lancet medical journal suggested that Tembexa didn’t provide a convincing benefit in three patients treated seven days after the initial onset of a rash. It’s uncertain whether giving it to people earlier or at a different dose would have led to different outcomes, the researchers said. The three patients treated with the drug also developed elevated liver enzymes — a sign of liver damage — and had to stop the therapy. 

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Chimerix said in a statement that the Lancet study was “limited by the low patient number and omission of notable background and context on the patients evaluated.” Another risk-benefit study, conducted by researchers associated with Chimerix, found that Tembexa was “generally well tolerated” in adults and children.

Drug Interactions

Tembexa, also known as brincidofovir, can also have adverse interactions when used with other medications, such as drugs for HIV. A recent update from the World Health Organization reported that over 40% of monkeypox patients whose HIV status was known were positive for that virus — rendering Tembexa’s use risky for them.

“The risk of increased mortality is serious and severe, and if given in other disease states where the safety and effectiveness of brincidofovir has not been established could result in an unfavorable benefit:risk profile,” FDA officials noted in a May 2021 safety review.  

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CDC’s Nordlund said in an email that “risks and benefits would need to be discussed and weighed carefully with patients and providers prior to initiating treatment with brincidofovir for monkeypox.”

As the global outbreak continues to spread, other countries are also looking to secure supplies of Tembexa. Chimerix said in a statement that it had seen “an uptick in interest,” including two non-US procurement contracts — one with Canada and the other outside North America. The company is in negotiations with the US Biomedical Advanced Research and Development Authority to include Tembexa in the US stockpile this year. 

Siga announced Tuesday that it had secured $28 million in procurement orders for Tpoxx, the bulk of which are contracts with Canada. Other orders came from a European country and another country in the Asia Pacific region, the company said in an email.