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Interferon therapy shows striking results against

COVID-19
Given early, one shot sliced hospitalization risk by half in large
trial

5 MAY 2022 • 4:00 PM • BY MEREDITH WADMAN

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From the earliest days of the pandemic, scientists have hoped that interferons, a family of potent proteins that
are the body’s own first line of defense against viruses, could become weapons against SARS-CoV-2. Because
the virus effectively blunts the interferon response, researchers thought providing extra interferons could
A man in Montes Claros, Brazil, is tested for SARS-CoV-2 before
counter it. But for 2 years, interferons have disappointed in trials in hospitalized patients.
being enrolled in a large trial of an interferon therapy in
2021. CARDRESEARCH/BELO HORIZONTE, BRAZIL

Now, a strikingly positive result from a large trial of nonhospitalized, high-risk people in Brazil has revived
hopes. In a study of more than 1900 people, those who received a single shot of a drug called peginterferon
lambda within 7 days of developing symptoms of COVID-19 were half as likely to be hospitalized or to endure
lengthy emergency room visits as those who received placebo. The effect, which the trial’s sponsor, Eiger
BioPharmaceuticals, reported in a press release, was seen across many SARS-CoV-2 variants, including
Omicron.

Eiger said today it plans to apply for an emergency use authorization for the shot from the U.S. Food and Drug
Administration by 30 June. It plans to make full data from the trial available at that time.

“If what they said in the press release is true, it is a very good result,” says Ivan Zanoni, an immunologist at Harvard Medical
School and Boston Children’s Hospital. But he is reserving 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 the Eiger injection did not reduce
symptom duration or the time it took people to clear the virus. The scientists who led that trial agree. “Until we see a peer-
reviewed publication, I am cautious re[garding] press release[s] from companies,” Upinder Singh, an infectious diseases
physician at the Stanford University School of Medicine, said in an email.

The caution may also reflect the discouraging results from trials of other kinds of interferons. Large trials sponsored by the
National Institutes of Health, the World Health Organization, and the company Synairgen all treated hospitalized patients,
and all failed.

The current trial was set up to catch patients early. That’s because interferons act in the earliest hours and days after viral
infection, kicking off a cascade of other proteins that attack the virus at every stage of its life cycle. Located at 12 sites in
Brazil, the trial targeted nonhospitalized patients who were older than 50 and/or were at higher risk of severe COVID-19
because they had conditions including 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.
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The company says 25 of 916 patients (2.7%) in the treatment arm were hospitalized or spent more than 6 hours in an
emergency room, compared with 57 of 1020 patients (5.6%) who received placebo. Eiger also reported that only one person in
the treatment group died, compared with four in the placebo group, although the number of deaths was too small to be
statistically meaningful.

“We believe we have a study that is highly generalizable to the current COVID environment in the U.S. and globally,” says Eiger
CEO David Cory. He says that whereas 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 those people with type 1 diabetes routinely self-administer—“has the
potential to be a one-and-done therapy, especially for high-risk patients.”

Based on 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 very hopeful that this may go somewhere.”

“From a basic science perspective, this is what was expected to happen,” Zanoni says.

Lambda interferons are type 3 interferons, which have receptors mainly on epithelial surfaces, such as those lining the
respiratory tract. The better 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 decided risk in a disease that, later in its course, can
tip patients into hyperinflammatory states.

In mice inoculated with SARS-CoV-2, inhaled lambda interferon limited viral infection throughout the respiratory tract
without causing excessive inflammation, a team based at Washington University School of Medicine in St. Louis reported in
Cell Reports on 15 April. And when the same team engineered mice to lack a receptor specific to lambda interferon-1 (IFNL-1)
—the protein in the Eiger product—their viral loads soared compared to mice with intact receptors.

Last year, Zanoni, and colleagues analyzed lung fluid and throat and nose samples from COVID-19 patients. IFNL1 appeared to
be associated with the most protective responses, keeping the virus corralled in the upper airways. “I was happy to see [Eiger’s
apparently successful interferon] was lambda 1 because that would have been our prediction,” Zanoni says.

Other scientists also note that the interferon response isn’t vulnerable to evolution of new, resistant SARS-CoV-2 variants,
unlike monoclonal antibodies, vaccine-induced immunity, or, perhaps, antiviral pills such as Paxlovid. “This is 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 ran a smaller trial of the Eiger drug in early-stage outpatients and found that a single injection sped
clearance of the virus. (Feld has received consulting fees from Eiger.)

Eleanor Fish, an immunologist at the University of Toronto who is an investigator on two unrelated trials of type 1 interferons
wonders whether a small company can make enough product to make a difference. “The results are good. My question is: Do
they have the capacity to actually make this available?” (The company says it expects to have 300,000 doses ready by the end
of this year.)

Feld, who treats patients at Toronto General Hospital, says if the data hold up, the Eiger drug’s all-purpose antiviral qualities
could make it useful for future respiratory disease pandemics. “While you are waiting for the very specific targeted therapy …
this is one to think about early because it’s very likely to have activity against most viruses.”

doi: 10.1126/science.adc8696

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H E A LT H C O R O N AV I R U S
ABOUT THE AUTHOR

Meredith Wadman  
Author

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