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Early treatment with a single dose of pegylated interferon lambda in a highly vaccinated population of COVID-19 outpatients decreased the risk for hospitalization and emergency department (ED) visits lasting more than 6 hours, the phase III TOGETHER trial found.

Among nearly 2,000 participants with acute COVID symptoms and a risk factor for severe illness, 2.7% of those who received pegylated interferon lambda within a week of symptoms required hospitalization or ED visits, as compared with 5.6% of those given placebo (relative risk [RR] 0.49, 95% Bayesian credible interval [CrI] 0.30-0.76), reported Gilmar Reis, MD, PhD, of McMaster University in Hamilton, Ontario, and colleagues.

Results were similar regardless of vaccination status (over 80% were vaccinated), and the treatment effect with the long-acting form of interferon lambda-1 was more pronounced in those who received the subcutaneous injection with 3 days of their symptoms.

Secondary endpoints demonstrated a lower risk for hospitalization and death in the interferon group (2.4% vs 3.9% with placebo; RR 0.61, 95% CrI 0.36-0.99), along with greater viral clearance by day 7 (OR 2.13, 95% CrI 1.14-4.00), the researchers detailed in the .

The vast majority of infections in the study, which was conducted primarily in Brazil, occurred during the Delta and Omicron waves, but results were consistent across strains.

"Resistance due to variants or new strains of the virus could be an issue with some therapies, but this may not be a concern with peginterferon lambda due to its mechanism of action that involves activation of multiple virus-killing pathways," said co-author Jordan Feld, MD, MPH, of Toronto General Hospital Research Institute, in a press release from developer Eiger BioPharmaceuticals.

Pegylated interferon lambda is an investigational, first-in-class type III interferon with broad-spectrum antiviral activity, according to the investigators, and has been shown to be well-tolerated in multiple clinical studies of COVID-19 and in hepatitis B, C, and D.

A prior in COVID-19 showed significant reductions in viral load with the product, and a safety profile similar to that of placebo injections. In the current trial, rates of adverse events (AEs) of any grade were similar for the treatment and placebo groups (15.1% vs 16.9%), as were rates of serious AEs (3.4% vs 4.8%).

For the pegylated interferon lambda arm of the multi-platform TOGETHER trial, 1,951 participants with a positive COVID-19 test and at least one high-risk factor for severe illness were included from 17 sites in Brazil and Canada, with enrollment beginning in June 2020. Patients with acute COVID-19 symptoms were randomized to a subcutaneous 180 μg pegylated interferon lambda injection or placebo (mostly injection, otherwise oral).

Median age of participants was 43 years, and 57% were women. Most were from Brazil (98.5%), with the remaining 1.5% from Canada. The vast majority of people were of mixed race (95%). Regarding vaccination, 50% had received two doses, 25% one dose, and 9% three doses.

Risk factors for severe COVID-19 illness included age 50 and older (39%), obesity (37%), and hypertension (30%), among others, and nearly 60% had multiple comorbidities.

Of the 931 patients in the interferon group, 25 had a primary-outcome event of hospitalization or an ED visit lasting more than 6 hours for COVID-19, as compared with 57 of 1,018 in the placebo group.

COVID-19 hospitalizations occurred in 21 participants in the interferon group and 40 in the placebo group, while deaths related to COVID-19 occurred in one and four patients, respectively.

Viral load at baseline did not correlate with treatment effect, the researchers noted, and median time to recover was 10 days in both groups.

In the 602 cases where the SARS-CoV-2 variant was known, most participants were infected with either the Delta (45.5%) or Omicron BA.1 (41%) variants, with the remaining infected by Gamma (12.5%), Alpha (0.8%), or Zeta (0.2%).

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