From the earliest days of the pandemic, scientists hoped that interferons, a family of powerful proteins that are the body’s first line of defense against viruses, could become weapons against SARS-CoV-2. Because the virus effectively dampens the response to interferon, the researchers thought that providing additional interferons might counteract it. But for the past 2 years, interferons have been disappointing in trials in hospitalized patients.
Now a surprisingly positive result from a large trial of high-risk non-hospitalized people in Brazil has revived hopes. In a study of more than 1,900 people, those who received a single injection of a drug called peginterferon lambda within 7 days of onset of COVID-19 symptoms were half as likely to be hospitalized or suffer longer emergency room visits than those who received a placebo. The effect, which the trial sponsor, Eiger BioPharmaceuticals, reported in a Press release, has been observed in many variants of SARS-CoV-2, including Omicron.
Eiger said today it plans to seek emergency use authorization for the vaccine from the U.S. Food and Drug Administration by June 30. He plans to make the full trial data available at that time.
“If what they said in the press release is true, that’s a really good result,” says Ivan Zanoni, an immunologist at Harvard Medical School and Boston Children’s Hospital. But he reserves judgment until a paper details the results, in part because a much smaller trial in younger outpatients with early, uncomplicated SARS-CoV-2 infection found that injecting Eiger did not reduce the duration of symptoms or the time it took people to clear the virus. The scientists who conducted this trial agree. “Until we see a peer-reviewed publication, I’m cautious[garding] Press release[s] businesses,” Upinder Singh, an infectious disease physician at Stanford University School of Medicine, said in an email.
The caution may also reflect the discouraging results of trials of other types of interferons. Major trials sponsored by the National Institutes of Healththe World Health Organizationand society Synairgen all inpatients treated, and all failed.
The current trial was set up to catch patients early. Indeed, the interferons act in the first hours and the first days following the viral infection, triggering a cascade of other proteins which attack the virus at each stage of its life cycle. Established at 12 sites in Brazil, the trial targeted non-hospitalized patients over the age of 50 and/or at higher risk for severe COVID-19 because they had diabetes, obesity, high blood pressure and lung disease. Eighty-four percent of participants were vaccinated. They received a single injection under the skin of placebo or peginterferon lambda, a drug Eiger was already developing to fight hepatitis D.
The company says 25 of 916 patients (2.7%) in the treatment group were hospitalized or spent more than 6 hours in the emergency room, compared to 57 of 1,020 patients (5.6%) who received a placebo. Eiger also reported that only one person in the treatment group died, compared to four in the placebo group, although the number of deaths was too small to be statistically significant.
“We believe we have a study that is highly generalizable to the current COVID environment in the United States and globally,” says Eiger CEO David Cory. He says that while the current leading antiviral, Pfizer’s Paxlovid, is given as a series of pills over 5 days, a single shallow injection of interferon – similar to what people with type 1 diabetes self-administer regularly – “has the potential to be a one-stop therapy, especially for high-risk patients.
According to the press release, the results are “quite impressive,” says Andreas Wack, an immunologist at the Francis Crick Institute who has studied the role of lambda interferons in COVID-19. “I’m hopeful that it can go somewhere.”
“From a fundamental scientific point of view, this is what was intended,” says Zanoni.
Lambda interferons are type 3 interferons, which have receptors primarily on epithelial surfaces, such as those lining the airways. The most well-known type 1 interferons act on every cell in the body, increasing the likelihood of off-target effects. They also promote inflammation more than type 3 interferons – a definite risk in a disease that later in its course can tip patients into hyperinflammatory states.
In mice inoculated with SARS-CoV-2, inhaled interferon lambda limited viral infection in the airways without causing excessive inflammation, a team based at Washington University School of Medicine in St. Louis reported in Cell reports April 15. And when the same team engineered mice that lacked a specific receptor for interferon lambda-1 (IFNL-1) — the product protein Eiger — their viral loads soared compared to mice with intact receptors.
Last year, Zanoni and his colleagues analyzed lung and throat and nose fluid samples from COVID-19 patients. IFNL1 seemed to be associated with the most protective responses, keeping the virus locked in the upper respiratory tract. “I was happy to see [Eiger’s apparently successful interferon] was lambda 1 because that would have been our prediction,” says Zanoni.
Other scientists also note that the interferon response is not vulnerable to the evolution of new resistant variants of SARS-CoV-2, unlike monoclonal antibodies, vaccine-induced immunity or, perhaps be, to antiviral pills such as Paxlovid. “It’s a host-targeting drug versus a virus-targeting drug…so resistance is really less of an issue,” says Jordan Feld, a hepatologist at the University of Toronto. He conducted a smaller trial of the drug Eiger in early-stage outpatients and found that a single injection speed set of the virus. (Feld received consulting fees from Eiger.)
Eleanor Fish, an immunologist at the University of Toronto and an investigator in two independent trials of type 1 interferons, wonders if one small company can manufacture enough products to make a difference. “The results are good. My question is: do they have the capacity to make this available? (The company says it expects 300,000 doses to be ready by the end of this year.)
Feld, who treats patients at Toronto General Hospital, says if the data holds, the versatile antiviral qualities of the drug Eiger could make it useful for future respiratory disease pandemics. “While you wait for the very specific targeted therapy…this is something to think about early because it is very likely to have activity against most viruses.”