PEG-Lambda a Boon to COVID-19 Patients

A single dose of a biological drug called pegylated lambda-interferon, delivered within a week of the start of COVID-19 symptoms, appears to significantly reduce the likelihood that a patient will end up hospitalized from the disease. A new study published in the New England Journal of Medicine highlights the impact of this drug and how it might be used to treat people going forward.

Pegylated lambda-interferon, or PEG-lambda for short, is the pharmaceutical counterpart to interferon lambda, a protein naturally secreted by cells in response to viral invasion. A multitude of clinical trials have demonstrated PEG-lambda’s ability to induce an immune response against a number of viruses, including various types of hepatitis and SARS-CoV-2. To build on the phase 2 studies exploring the impact of PEG-lambda on SARS-CoV-2 viral load, a team of scientists conducted a large international randomized phase 3 trial comparing outcomes for patients diagnosed with COVID-19 who received PEG-lambda with those who received placebo only. The study’s primary composite endpoint was hospitalization or an emergency room visit due to COVID-19 infection, with either occurring within 28 days of randomization.

The study included adult patients suffering from severe COVID-19 symptoms who presented to outpatient clinics within a week of first feeling ill. Those included in the trial had at least 1 risk factor for poor COVID-19 outcomes, including being at least 50 years old, having diabetes, having hypertension serious enough to warrant medication, having cardiovascular disease, and smoking. As many as one quarter of participants were enrolled despite not having any of these risk factors because their COVID-19 symptoms were particularly debilitating.

All 931 participants in the PEG-lambda cohort received a single subcutaneous injection of PEG-lambda, while the 1018 participants in the placebo cohort received an injection of saline or, less commonly, a capsule or tablet placebo. Nasal swabs were taken at baseline and on days 3 and 7 at clinical sites in Brazil, while participants at Canadian sites had nasal swabs taken daily for 2 weeks.

Twenty-five of the 931 subjects (2.7%) who received PEG-lambda experienced either hospitalization or an ER visit compared with 57 out of the 1018 subjects (5.6%) who received placebo, translating to a risk reduction of 51%. These events, three-quarters of which were hospitalizations, occurred after a median of 5 days. Narrowing the analysis to subjects who received either PEG-lambda or placebo within 3 days of the onset of COVID-19 symptoms, the impact of treatment was even more significant: 11 out of 567 subjects (1.94%) receiving PEG-lambda had a primary-outcome event vs. 28 out of 590 subjects (4.75%) receiving placebo. The virologic effect was notable as well: Participants with high viral loads who got a shot of PEG-lambda saw their viral levels drop more than those in the placebo group.

How does PEG-lambda compare with Paxlovid, which is sometimes prescribed for people suffering from COVID-19? “Unlike Paxlovid, which is 30 pills over 5 days, lambda is 1 dose and you’re done,” Jeffrey Glenn, MD, PhD, professor of medicine and of microbiology and immunology and director of ViRx@Stanford, told Contagion. Glenn, who founded and is on the board of Eiger BioPharmaceuticals, which developed lambda-interferon to battle hepatitis, added that PEG-lambda induces an immune response against all COVID-19 variants and caused no more side effects among study participants than the placebo did. In contrast, Paxlovid can have numerous side effects as well as inhibit the metabolism of other drugs, which may be a special concern for senior citizens. “The older you get, the more likely it is that you’re on medication,” he noted.

The small percentage of trial participants who were not vaccinated against COVID-19 reaped an even higher level of protection from PEG-lambda than those who were vaccinated: For subjects receiving PEG-lambda within 3 days of symptom onset, the reduction in hospitalization or death compared with the placebo group was 89%, Glenn said, meaning that for people who can’t or won’t get vaccinated against COVID-19, PEG-lambda may be especially protective.

PEG-lambda is not yet authorized by the FDA.