From the early days of the epidemic, scientists had hoped that interferons, a family of powerful proteins that make up the body’s first line of defense against viruses, would become weapons against SARS-CoV-2. Because the virus effectively suppresses the interferon response, the researchers thought that providing additional interferon could combat it. But for two years, interferon disappointed in trials in hospitalized patients.
Now, a strikingly positive result from a large trial of non-hospitalized, high-risk people in Brazil has revived hopes. In a study of more than 1,900 people, those who received a single dose of a drug called lambda peginterferon within 7 days of developing symptoms of COVID-19 were more likely to be admitted to hospital or to endure extended visits to the emergency room as those who received a placebo. . The effect, announced by the trial sponsor, Eiger BioPharm Pharmaceuticals, in a press releaseAnd It has been seen across several SARS-CoV-2 variants, including Omicron.
Today, Eiger said he plans to file an emergency use authorization application for the ring from the U.S. Food and Drug Administration by June 30. It plans to make the full data from the experiment available at that time.
“If what they said in the press release is true, that’s a very good result,” says Evan Zanini, MD, an immunologist at Harvard Medical School and Boston Children’s Hospital. But he’s keeping the judgment until a paper detailing the results, in part because a much smaller trial in younger outpatients with early, uncomplicated SARS-CoV-2 infections found that the Egger shot did not reduce the duration of symptoms or the time it took for people to clear the virus. The scientists who led this experiment agree. “Until we see a peer-reviewed post, I am wary of it[garding] press release[s] Upinder Singh, an infectious disease physician at Stanford University School of Medicine, said in an email.
Caution may also reflect disappointing results from trials of other types of interferon. Large trials sponsored by the National Institutes of Health, the World Health Organization and Synergen have treated all inpatients, and all failed.
The current trial was set up to catch patients early. That’s because interferon works in the first hours and days after a viral infection, releasing a cascade of other proteins that attack the virus at every stage of its life cycle. Located in 12 locations in Brazil, the trial targeted non-hospitalized patients over 50 years of age and/or who were at increased risk of severe COVID-19 because they had conditions such as diabetes, obesity, high blood pressure and lung disease. 84 percent of the participants were vaccinated. They received a single subcutaneous injection of a placebo or peginterferon lambda, a drug Iger was already developing to combat hepatitis D.
The company says that 25 of the 916 patients (2.7%) in the treatment arm were hospitalized or spent more than 6 hours in the emergency room, compared with 57 of the 1,020 patients (5.6%) who received the placebo. Egger 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 highly generalizable study of the current COVID environment in the United States and globally,” says David Cory, CEO of Eiger. 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 people with type 1 diabetes routinely — “has the potential to be A one-time treatment drug, especially for high-risk patients.”
Based on the press release, the results are “absolutely impressive,” says Andreas Wack, an immunologist at the Francis Crick Institute, who has studied the role of lambda interferon in COVID-19. “I am very optimistic that this might go somewhere.”
“From a basic scientific perspective, this is what was expected to happen,” Zanoni says.
Lambda interferons are type III interferons, and have receptors mainly on epithelial surfaces, such as those lining the respiratory tract. The most known type of interferon affects every cell in the body, increasing the potential for off-target effects. They also promote inflammation more than type III interferon — a prescribed risk in a disease that, later in its course, can direct patients to highly inflammatory states.
A team from Washington University School of Medicine in St. Louis reported that in mice vaccinated with SARS-CoV-2, lambda interferon inhaled limited viral infection throughout the respiratory tract without causing excessive inflammation. cell reports On April 15th. And when the same team engineered mice that lacked the receptor for lambda interferon-1 (IFNL-1) — the protein in the Eiger product — their viral loads increased compared to mice with the healthy receptor.
Last year, Zanoni and his colleagues analyzed lung fluid and throat and nose samples from COVID-19 patients. IFNL1 appears to be associated with the most protective response, keeping the virus circulating in the upper airways. “I was happy to see [Eiger’s apparently successful interferon] It was lambda 1 because that was our expectation,” says Zanoni.
Other scientists have also noted that the interferon response is not prone to the development of new variants that are resistant to SARS-CoV-2, unlike monoclonal antibodies, vaccine-induced immunity, or possibly antiviral pills such as Paxlovid. “This is a host-targeting drug versus a virus-targeting drug … so resistance is really not an issue,” says Jordan Field, a hepatologist at the University of Toronto. He conducted a smaller outpatient trial of Egger in the early stages and found that a single injection speeds up the removal of the virus. (Field received a consulting fee from Iger.)
Eleanor Fish, an immunologist at the University of Toronto who is an investigator of two unrelated trials of type 1 interferon, wonders if a small company could make enough product to make a difference. “The results are good. My question is: Do they really have the ability to make that available?” (The company says it expects to have 300,000 doses ready by the end of this year).
Field, who treats patients at Toronto General Hospital, says that if the data holds up, the all-purpose antiviral properties of Iger could make it useful for future respiratory disease epidemics. “While waiting for a very specific targeted therapy … this should be considered early because it is very likely to have activity against most viruses.”