A new Phase 3 study conducted by the international team of drug researchers behind the TOGETHER Trial has found that patients infected with COVID-19 were significantly less likely to be hospitalised or visit emergency departments when treated early with the antiviral drug pegylated interferon lambda.
The large-scale randomised, placebo-controlled trial involving predominantly vaccinated adults with COVID-19 found there to be a 51 percent reduction in hospitalisation or emergency department visits among patients who received a single subcutaneous dose of pegylated interferon lambda, compared with those in the placebo group.
Importantly, throughout the trial - which was conducted between June 2021 and February 2022 - multiple new COVID-19 variants had emerged. Early treatment with pegylated interferon lambda was found to be effective across the dominant variants, which is significant given that the emergence of new variants has threatened the efficacy of many therapeutic agents, thus creating an urgent need for alternative treatment options.
The study, published in The New England Journal of Medicine, was led by Dr Gilmar Reis and Dr Edward Mills of Canada's McMaster University and Dr Jeffrey Glenn of Stanford University, and included Dr Craig Rayner, an Adjunct Research Professor with the Monash Institute of Pharmaceutical Sciences, who has been a Senior Investigator on the TOGETHER Trial since its inception. The TOGETHER Trial aims to identify effective repurposed therapies to prevent the disease progression of COVID-19.
A total of 933 patients were randomly assigned to receive pegylated interferon lambda and 1018 were randomly assigned to receive placebo.
Dr Rayner said that the identification of convenient, widely available, and effective antiviral therapies against COVID-19 for outpatients is of great importance.
"With the World Health Organisation recently declaring the COVID-19 pandemic to be far from over and new variants continuing to threaten the current treatment toolkit, the findings from this study are exciting. As COVID continues to rage on, there is an urgent global need for new and accessible solutions to prevent death and improve health outcomes for all people affected by COVID-19," said Dr Rayner.
"In infected cells, COVID-19 induces weak expression of naturally produced type III interferons, which are an early line of defence in upper respiratory tract infections. Treatment with an exogenous source of interferon lambda such as pegylated interferon lambda could stimulate antiviral immunity and treat early SARS-CoV-2 infection."
"We also found that among patients with a high viral load at baseline, those who received pegylated interferon lambda had lower viral loads by day seven than those who received placebo, thus slowing the progression of the disease and decreasing the likelihood of it escalating into something more serious."
In more than 20 clinical trials, the administration of pegylated interferon lambda to more than 4000 patients for a variety of conditions (including hepatitis B, C, and D, and Covid-19) has provided a well-understood safety and side-effect profile.
The results of two phase 2 studies characterising the effect of pegylated interferon lambda on COVID-19 viral load have already been published. To further evaluate the effect of this agent on clinical outcomes, the team behind the TOGETHER Trial conducted a large, Phase 3, randomised, placebo-controlled adaptive platform trial involving outpatients with Covid-19 in Brazil and Canada.
Dr Rayner is a Monash University Faculty of Pharmacy and Pharmaceutical Sciences Adjunct Research Professor and Distinguished Alumnus and has recently joined Moderna Australia as Director, Regional Centre for Respiratory Medicine and Tropical Disease.
