Immunotherapies at the Forefront of COVID-19 Treatment Research
MAY 05, 2020
Adam Friedman, MD
During a free online webinar hosted by HCPLive® and sister publication Dermatology Times titled “Derm Clinical Updates: Keeping Up with COVID-19,” Adam Friedman, MD, Professor & Interim Chair of Dermatology at The George Washington University School of Medicine and Health Sciences, said most of the promising treatments in clinical trials focus on immunotherapies commonly used in dermatology.
“I think this is where we are going to have the strongest impact and as dermatologists we can have a lot of input here because manipulation on the immune system is our bread and butter,” Friedman said. “The reason why this viral infection is so impactful and it’s killing people left and right is not the infection itself and what it’s doing, it’s rather the immune response as well.”
Friedman explained that there are generally 3 different categories of treatments to test as a potential therapeutic for COVID-19—antivirals, immunotherapies and anti-cytokine storm treatment, and vaccines. Immunotherapies may actually have a protective effect for patients, bringing them to the front of the line of potential treatments.
At the time of the webinar, there were approximately 14 antiviral treatments either in development or actively being studied.
The US Food and Drug Administration (FDA) recently issued an emergency use authorization (EUA) for remdesivir, an antiviral drug with promise treating COVID-19.
Remdesivir, a broad-spectrum antiviral agent, was initially developed to treat upper respiratory viral infections.
The drug is an adenosine analogue that inserts into viral RNA chains to cause premature terminations.
Recently, a double-blinded, placebo-controlled trial, along with 2 other phase 3 trials evaluated the safety and efficacy of the drug in treating adults with COVID-19 infections, where patients received up to 10 days of treatment with 200mg of remdesivir intravenously on day, followed by 100 mg daily during hospitalization or placebo.
Friedman also mentioned a small study published in the New England Journal of Medicine where severe COVID-19 patients were treated with compassionate-use remdesivir. In this study, investigators identified clinical improvement in 36 of 53 patients (68%).
However, it is far from certain that this treatment is both safe and effective for COVID-19 patients.
“Most of the data out there is non-peer reviewed and that makes sense, we are trying to get the data out there as quickly as possible,” Friedman said. “I think the majority of the evidence is certainly supportive, but it does go back and forth depending on the day. It all depends on your inclusion criteria.”
One of the more positive trials was released by Gilead, showing that five-day treatment with remdesivir was analogous to 10-day dosing.
While remdesivir has had positive reports, there are other treatments being tested that could be safe and effective in treating patients who contract the virus.
One of the immunotherapy drugs being tested is tolucizumab, a monoclonal antibody against interleukin-6 receptor (IL-6r). Excessive IL-6 can cause a “cytokine storm” that activates the coagulation pathway and vascular endothelial cells, while inhibiting myocardial function.
Infections by the related SARS-CoV induces a dose-dependent production of IL-6 from bronchial epithelial cells.
This medication does have an FDA approval in-hand for the treatment of severe or life-threatening cytokine release syndrome caused by CAR T-cell therapy. Friedman said there is some initial positive data regarding this treatment, but it has yet to be peer reviewed.
Other options might be sarilumab, which has the same receptor as tolucizumab with only the rheumatoid arthritis indication, anakinra, and baricitinib, a JAK inhibitor approved for rheumatoid arthritis that could also prevent invasion of the virus.
Another treatment initially thought to be effective was hydroxychloroquine, an anti-malaria treatment that is also used for lupus and arthritis.
While recent data has been murky regarding this treatment, Friedman said it is a favorite of his as a benefit to dermatology patients.
“We can use it for so many things and works really well and it’s pretty safe in the grand scheme of things,” Friedman said. “It’s been around for a long time, which gives us a lot of credibility when we’re talking about that safety profile.”