Peginterferon-lambda shows strong antiviral action to accelerate clearance of COVID-19

A clinical study led by Dr. Jordan Feld, a liver specialist at the Toronto Center for Liver Disease, University Health Network (UHN), has shown that an investigational antiviral drug can dramatically speed the recovery of ambulatory patients from COVID-19 – the patients who do not need to be hospitalized.

It could become an important intervention to treat infected patients and help curb the spread in the community, as COVID-19 vaccines are rolled out this year.

“This treatment has great therapeutic potential, especially at this time, as we are seeing aggressive variants of the virus spreading around the world, which are less susceptible to vaccines and antibody therapy,” says Dr Feld, also co-director from the Schwartz Reisman Liver Research Center and the R. Phelan Chair in Translational Liver Research at UHN.

According to the study, published today in Lancet respiratory medicine, patients who received a single injection of peginterferon-lambda were more than four times more likely to have cleared the infection within seven days, compared to a group treated with placebo.

“Those treated quickly cleared the virus, and the effect was most pronounced in those with the highest viral levels. We also saw a trend for faster improvement in respiratory symptoms in the treatment group, ”says Dr Feld, who translated his knowledge. from the use of lambda peg-interferon for viral hepatitis to research into COVID-19 treatment

Participants with higher viral levels (greater than 1 million copies per mL) were much more likely to clear the infection with treatment than placebo: 79% in the treatment arm compared to 38% in the placebo group; and virus levels declined rapidly in everyone in the treatment group.

Benefits of treatment and impact on public health

Rapid clearance has many benefits, especially in people with high viral levels, as these cases are associated with more serious illness and a higher risk of transmission to others. Of the 60 patients followed in the study, five went to the emergency room with worsening respiratory symptoms. Of these, four were in the placebo group, while only one was in the group that received the drug itself.

Reducing the level of the virus quickly keeps people from getting worse and likely lowers the risk of spreading the disease to others. This can have a significant additional impact on public health.

“If we can quickly reduce the level of the virus, people are less likely to spread the infection to others and we may even be able to shorten the time it takes for self-isolation,” says Dr Feld.

Interferon-lambda

Interferon-lambda is a protein produced by the body in response to viral infections. It has the ability to activate a number of cellular pathways to kill invading viruses.

The coronavirus that causes COVID-19 prevents the body from making interferons, which avoids being controlled by the body’s immune system. Interferon-lambda treatment activates these same virus destruction pathways in cells.

Because interferon activates many virus destruction pathways, resistance to “new strains” of the virus, which could be a problem with some therapies, is not a problem with lambda interferon.

Interferon-lambda is different from other interferons because it uses a receptor that is only present in certain tissues in the body. It is very active in the lungs, liver, and intestine, all places where the COVID-19 virus is able to replicate, but it is not active elsewhere, causing far fewer side effects than other interferons. . In the trial, people treated with interferon-lambda had side effects similar to those who received a placebo.

Peginterferon-lambda (used in this study) is a long-acting version of the drug developed by Eiger BioPharmaceuticals, which can be given as a single injection under the skin with a small needle (like insulin).

Next steps

This was a randomized, double-blind, investigator-initiated phase 2 study in Toronto with a total of 60 participants – 30 who received the drug and 30 received a placebo. The study was conducted from May to November 2020, with referrals from six outpatient assessment centers.

With these positive results, a large phase 3 trial is expected to start in the near future. Additional studies are underway at the University of Toronto, Harvard University and Johns Hopkins University on peginterferon-lambda in hospital patients and in settings where it can be used to prevent infection in those that have been exposed.