One-and-done injection halves risk of COVID hospitalization in large trial
A one-time shot with an experimental drug halved COVID-19 patients' risk of being hospitalized with the illness compared with a placebo, a late-stage trial shows. However, the treatment may still be early in its journey to approval in the U.S., the drug's maker told Live Science.
The trial participants received an injection of the drug, called pegylated interferon lambda (PEG-lambda), within one week of developing COVID-19 symptoms. Those who received PEG-lambda early, within the first three days of developing symptoms, reaped the most benefit: Overall, these individuals were 65% less likely to be hospitalized in the following month. Among the subset of these individuals who were unvaccinated, the risk of hospitalization fell by about 89%, compared with a placebo.
Pfizer's antiviral pill Paxlovid (generic name nirmatrelvir) also lowers unvaccinated people's risk of hospitalization by about 89%, according to a late-stage trial that helped the drug earn emergency use authorization (EUA) from the Food and Drug Administration (FDA). However, one major difference between PEG-lambda and Paxlovid is that, while the former is a one-and-done injection, the latter requires users to take three tablets twice a day for five days, which totals 30 pills.
While the Paxlovid regimen may be difficult for patients to stick to, "[PEG-lambda] has 100% compliance, by definition, because it's one dose and you're done," said Dr. Jeffrey Glenn, a professor of medicine and of microbiology and immunology at Stanford University School of Medicine, and the director of ViRx@Stanford, which develops antiviral agents to prepare for potential pandemics.
And while Paxlovid targets the coronavirus SARS-CoV-2, PEG-lambda theoretically raises the immune system's first line of defense against many pathogens, which reduces the chances that the virus will evolve resistance to it, Glenn said.
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Glenn is the senior author of a new report, published Wednesday (Feb. 8) in the New England Journal of Medicine, which describes the trial data in detail. Glenn also founded Eiger BioPharmaceuticals, the drug's maker, and he currently sits on the company's board.
PEG-lambda contains a type of protein known as a type III interferon, which the body naturally produces in response to viral invasion. Once released, these proteins travel to cell surfaces, where they lock into receptors. Latching onto these receptors sets off a chain reaction inside the cell that ultimately raises its guard against viruses, making it more difficult for pathogens to infiltrate cells, replicate and spread.
The interferon within PEG-lambda specifically binds to receptors found in tissues lining the lungs, airways and gut, as well as the liver — all prime targets for SARS-CoV-2. The drug combines this interferon with polyethylene glycol, which slows the rate at which the interferon gets cleared from the body. PEG-lambda hangs around in the body for at least a week after injection, Glenn said.
The late-stage trial of PEG-lambda took place in Brazil and Canada and included more than 1,900 participants between ages 18 and 92. All the participants tested positive for SARS-CoV-2 on a rapid antigen test and were treated at outpatient clinics within seven days of developing COVID-19 symptoms. The majority had at least one characteristic that put them at high risk of severe infection, including a history of diabetes, smoking or lung disease. Around 83% of the participants had received at least one dose of a COVID-19 vaccine, and up to three doses.
About 930 participants received an under-the-skin injection of PEG-lambda, and of these, 25 were hospitalized or had a lengthy emergency room visit due to COVID-19 in the following month. That's compared with 57 people out of about 1,020 in the placebo group — or a 51% difference in hospitalization risk between the groups.
The trial took place between June 2021 and February 2022, and genetic analyses suggested the participants were infected by a variety of SARS-CoV-2 variants, including alpha, delta, gamma, zeta and the BA.1 lineage of omicron. PEG-lambda fared equally well against all these variants. And again, because the treatment boosts human cells' defense systems, rather than targeting SARS-CoV-2 directly, future variants aren't likely to develop resistance to the drug, as they might against other antivirals, Glenn said.
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Although this positive data has now been published in a peer-reviewed journal, PEG-lambda still faces barriers to approval in the U.S. In October 2022, Eiger announced that it had requested a pre-EUA meeting with the FDA and had been denied. At that time, the FDA cited concerns about the "conduct" of the clinical trial and noted that, "in the current context of the pandemic," it would be unlikely to issue an EUA based on that trial's data.
The concerns about the trial's conduct were related to the fact that PEG-lambda was tested through the TOGETHER Trial, an international effort launched in the early days of the pandemic to test a slew of potential COVID-19 treatments, Ingrid Choong, Eiger's senior vice president of clinical development, told Live Science.
Typically, to earn FDA authorization, a company runs its own trial start to finish; collaborates with the FDA to set the protocols ahead of time; and periodically sends experts to each study site to ensure rigorous, industry standards are being followed. The FDA didn't have the same level of oversight over the TOGETHER Trial, and in addition, by the time Eiger was preparing to apply for an EUA, the urgency of the pandemic in the U.S. had somewhat "waned," Choong noted.
"In the context of the pandemic, I think it was really the right thing to do, to provide the drug, to try and generate important data during the crisis," Dr. David Apelian, Eiger's interim chief executive officer, told Live Science. And "I think the data show the utility of the treatment."
At this point, Eiger may seek the emergency use authorization for PEG-lambda in countries beyond the U.S., and the company is currently evaluating how it might pursue traditional approval in the U.S., as the FDA has suggested. To that end, rather than going after only COVID-19, the company may consider testing the interferon as a "panviral" treatment that can be used against many viruses, Apelian said.
"It's pretty likely that this could work in a similar fashion for flu and for RSV [respiratory syncytial virus], so I would see that as maybe a more prudent way of developing this through a traditional path," Apelian said. (Separately, Eiger will also continue testing the drug's effectiveness against hepatitis D, he noted; the liver disease was the first condition the company attempted to treat with PEG-lambda.)
Glenn echoed the idea of using PEG-lambda as a broad-spectrum treatment for many respiratory viruses. "I hope we will see a study designed to show how lambda can counter all the viruses in the 'tripledemic'," referencing the flu, RSV and COVID-19, Glenn told Live Science.
In addition, Glenn said he is interested in trialing the drug as a treatment for long COVID. There's evidence that at least some symptoms of long COVID stem from residual virus lingering in the body, according to a report published Jan. 13 in the journal Nature Reviews Microbiology, and Glenn wonders if PEG-lambda could help clear these reservoirs.