In This Article
- Pegylated interferon lambda (PEG-IFN-lambda) is a potent antiviral cytokine that acts to generate an antiviral state within many cell types
- A new investigator-initiated trial at Massachusetts General Hospital will evaluate the use of the PEG-IFN-lambda to treat these patients
- In this Q&A, Raymond Chung, MD, explains what is currently known about the antibody therapeutic and why he is excited about its potential to treat COVID-19 patients
While there are many antibody-based therapeutics in clinical trials for COVID-19, there are currently no FDA approved antibody therapies. A new investigator-initiated trial at Massachusetts General Hospital will evaluate the use of the antibody pegylated interferon (PEG-IFN)-lambda to treat these patients. The trial is led by Raymond Chung, MD, vice chief of the Gastrointestinal Division and director of the Hepatology and Liver Center at Mass General, who has a background in studying infection control in HCV and HIV. In this Q&A, Dr. Chung explains what is currently known about the antibody therapeutic and why he is excited about its potential to treat COVID-19 patients.
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Q: What do we know about using pegylated interferon lambda today?
Chung: Pegylated-interferon-lambda is a potent antiviral cytokine that acts to generate an antiviral state within many cell types. Other IFN therapeutics have been used to treat disease. Specifically, IFN-alpha to treat some forms of cancer and IFN-beta to treat multiple sclerosis. Compared to the more commonly used alpha and beta, lambda has a more restricted receptor distribution in epithelial cells (like the lung) but not immune or bone marrow cells, and its use is therefore associated with fewer systemic side effects, as shown in a 2016 study published in SpringerPlus that found lower numbers of flu-like symptoms and hematological abnormalities.
Q: What do we know about its use to treat patients with coronavirus?
Chung: Interferons including IFN-lambda, have demonstrated potent antiviral effects against various viruses including coronaviruses in cell culture and in animal models. In Frontiers of Immunology, it's reported that mice have shown potent antiviral effects of IFN-lambda against influenza and SARS coronavirus, rotavirus, norovirus and reovirus. In a study published in the Journal of General Virology, it was found that type I (alpha, beta) and type III (lambda) IFN signaling is crucial for controlling SARS-CoV replication in the lung. And in EMB Molecular Medicine, IFN-lambda was found to be a better treatment option (vs. IFN-alfa) for influenza A virus-induced disease.
In clinical trials against the coronavirus that caused SARS in 2003, interferon also demonstrated efficacy in combination with steroids. Published in JAMA, the combination therapy led to improved oxygen saturation (resolved need for supplemental oxygen faster; median, 10 days vs. 16 days), faster repair of lung abnormalities on x-ray (median time, 4 days vs 9 days; P=.001) and lower creatinine levels.
Q: Why was this drug prioritized to be one of the first COVID-19 trials at Mass General?
Chung: We chose this compound because of the strength of its preclinical data and the precedent for interferon's clinical efficacy against other coronaviruses, and the finding published in Cell that in the early stages of human SARS-CoV-2 infection, there is a weak interferon response. All of this led us to believe that IFN-lambda could play an important role as an antiviral agent in COVID-19.
Q: What are the potential drawbacks or reservations associated with use of this drug?
Chung: Interferons, even those with more limited side effects such as lambda, could theoretically tweak an immune response that in some cases may already be hyperactivated as seen with alpha and beta. We need to demonstrate its safety in this trial.
Q: What is Mass General's role in clinical trials with this drug?
Chung: I am leading an investigator-initiated single-center pilot protocol clinical trial at Mass General exploring PEG-IFN-lambda's antiviral efficacy in hospitalized patients with COVID-19. The trial has been greenlighted by the FDA and received IRB approval. If safety and proof of concept is demonstrated, then plans for expansion to a larger, multicenter trial will follow with potential extension into non-hospitalized patients.
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