A new antiviral called pegylated interferon lambda (PEG-lambda) shows great promise as a COVID-19 treatment, reducing the risk of hospitalization by roughly 50%. However, regulatory hurdles and limited funding may hinder its ability to enter the U.S. market.

A promising new COVID-19 treatment

According to Scientific American, PEG-lambda is a synthetic version of proteins called interferons, which are signaling molecules part of the body's innate immunity. Cells produce interferons when a pathogen enters the body to quickly activate immune defenses.

Lambda interferons in particular have receptors specifically on epithelial cells, which are found in the lungs and airways where the coronavirus tends to replicate. By boosting interferons, "the awakened immune system will take care of the intruder by itself," said Ludmila Prokunina-Olsson, a geneticist from the National Cancer Institute.

PEG-lambda, which was initially developed by Eiger BioPharmaceuticals for viral hepatitis, is administered as a single subcutaneous injection. The protein is attached to a molecule that slows down its removal from the blood.

To test the efficacy of the treatment, Eiger recruited independent researchers from the TOGETHER Trial network. The trial, whose results were recently published in the New England Journal of Medicine, was conducted in both Canada and Brazil, and included almost 2,000 patients. Over 80% of participants were vaccinated, and most had at least one characteristic that put them at a higher risk of severe COVID-19, including older age, smoking, or heaving a health condition such as heart disease or diabetes.

Of the participants, 931 received the treatment, and 1,018 received a placebo. Overall, the researchers found that participants who received PEG-lambda within seven days of their symptoms were 51% less likely to go to the ED or be hospitalized compared to those who had received a placebo.

Among participants who received the treatment within three days of their symptoms, there was a 58% reduction in hospitalization risk. The effect was even more pronounced among unvaccinated patients who received the treatment within three days; they had an 89% reduction in hospitalization risk.

Because the trial spanned multiple COVID-19 surges, it was tested against several different variants. Although it was most effective against the omicron variant, "it worked across all variants," said Jeffrey Glenn, senior author of the study from Stanford University who originally founded Eiger.

"Despite the pandemic being less of an emergency than it was at its peak, we're still seeing people coming into the hospital and getting very sick with Covid," said Jordan Feld, a specialist in viral hepatitis at the University of Toronto and a co-author of the study. "Having treatment options to try to prevent that from happening would be really helpful."

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According to Evangelos Andreakos, an immunologist from the Academy of Athens, the trial was "well-designed, well-controlled," and confounding factors, such as age, race, and comorbidities, were all taken into account.

"The findings are convincing," Andreakos said.

Because PEG-lambda targets the immune system instead of the virus itself, some experts suggest that it could reduce the risk of a variant evolving to resist the treatment, giving it an advantage over existing treatments. It could also be effective against other viruses, not just the coronavirus.

"I don't know of any virus that can navigate a cell where interferon got there first," said Benjamin tenOever, a microbiologist at the NYU Grossman School of Medicine.

"It doesn't matter if the next pandemic is a coronavirus, an influenza virus, or another respiratory virus," said Eleanor Fish, an immunologist at the University of Toronto. "For all the viruses we're seeing that are circulating now, there's utility to using interferon."

Why it may not be authorized for use in the US

Although Eiger had initially planned to seek emergency use authorization from FDA, this may not currently be possible.

According to the New York Times, Eiger executive said one issue was that the clinical trial had only been conducted in Canada and Brazil without a U.S. site as well. In addition, the trial was initiated and run by academic researchers instead of the company.

To conduct a large clinical trial at least partly in the United States and with more involvement from Eiger itself would "require several years and considerably more funding," the Times writes. Because of this, company leaders said they may seek authorization for PEG-lambda outside of the United States instead.

"I think it is a crazy situation that we're still here now, three years into the pandemic, and I have one drug that I can prescribe with confidence to people who are getting infected," Glenn said. "We need more options." (Mueller, New York Times, 2/8; Makin, Scientific American, 2/8; Reis et al., New England Journal of Medicine, 2/9)