Jeffrey S. Weber, MD, PhD, Discusses Anti-IL-6 Agents in Treating COVID-19-Induced Pneumonia

The deputy director at NYU Langone’s Perlmutter Cancer Center explained the importance of these agents and the development of clinical trials in this setting.

Anti-IL-6 agents have been suggested to treat critically ill patients with coronavirus disease 2019 (COVID-19) pneumonia, sparking the development of randomized clinical trials to quickly evaluate the safety and efficacy of these agents in treating the virus. 

Jeffrey S. Weber, MD, PhD, deputy director at NYU Langone’s Perlmutter Cancer Center and co-director of the Melanoma Research Program, explained that these agents are being explored because a small portion of patients who are infected with COVID-19 have a cytokine storm syndrome. 

“It’s just this violent release of substances that normally are utilized by the immune system for good purposes, and they are so vigorously secreted by immune cells that they cause detrimental consequences to the body. It’s kind of what happens when you have sepsis, meaning you have a blood infection and the bacteria, for example, start to grow in the blood,” Weber said. “It’s just an overly vigorous immune response.”

Weber was first presented with the idea of using anti-IL-6 agents to treat patients with COVID-19 pneumonia by his colleague Paolo Ascierto, MD, of the National Tumour Institute “Fondazione G. Pascale” in Naples. Ascierto has been assessing the use of anti-IL-6 agents like tocilizumab (Actemra) in this patient population, indicating that their use has led to improvements.

Being 67 years of age, Weber was told that he cannot volunteer during the COVID-19 pandemic; so instead, he decided to pen a commentary based on Ascierto’s findings to hopefully inform US studies. The Society for Immunotherapy of Cancer (SITC) then used Weber’s paper as a basis for their call to allow anti-IL-6 agents on a compassionate basis to treat hospitalized critically ill patients infected with COVID-19.1

According to SITC, the use of IL-6 or IL-6 receptor blocking antibodies like tocilizumab, sarilumab (Kevzara), and siltuximab (Sylvant) that are FDA approved to treat various conditions including rheumatologic disease and the lymphoproliferative disorder Castleman’s syndrome could potentially be used to treat hospitalized critically ill patients with COVID-19-induced hypoxia. 

“I think the gist of it is that we’re at war, and we need to move quickly and get these drugs, which have a theoretical promise, into patients,” said Weber. “I think the big issue and the reason why I wrote that editorial is that my Italian colleagues were telling me they were having difficulty getting access to some of the drugs and they were convinced that the drugs were useful based on their anecdotal experience.”

Investigators in Italy and China have used tocilizumab to treat patients infected with COVID-19 at doses comparable to those used for the management of cytokine release syndrome, reporting rapid improvements in both intubated and non-intubated patients. However, in these reports, the expedited administration of anti-IL-6R therapy for patients in acute respiratory distress has been essential.

Weber indicated that though data from ongoing trials of anti-IL-6 agents in Europe should be released shortly, the US has also decided to move forward with placebo-controlled trials; which begs the question, why are units around the US doing randomized trials if Italy should have the data needed shortly? Weber suggests that perhaps a more creative trial design could be conceived in order to more quickly evaluate these therapies. 

“I’m a classically trained investigational clinical trialist in oncology, so I appreciate the value of the randomized, blinded, placebo-controlled study, but that’s an awfully tough-to-sell sales pitch when you’re desperately ill,” said Weber. “So, it makes me wonder, are there any alternatives to doing a randomized phase III placebo-controlled trial? Could there be a short-term endpoint in a phase II study that would convince physicians that tocilizumab or sarilumab was useful in these patients?”

Thus far, in the US, a trial of sarilumab in the COVID-19 setting remains ongoing. Additionally, several independent clinical trials have begun globally to explore the efficacy and safety of tocilizumab in patients with COVID-19 pneumonia.2

Recently, the FDA approved a randomized, double-blind, placebo-controlled phase III study of intravenous tocilizumab plus standard of care in hospitalized adult patients with severe COVID-19 pneumonia. Enrollment for this trial is anticipated to begin in April 2020, with a target accrual of 330 patients across the US and other countries. 

In China, tocilizumab was approved in March 2020 for the treatment of patients infected with COVID-19 who experienced serious lung damage and elevated IL-6. 


1. SITC. Insights from immune-oncology: The Society for Immunotherapy of Cancer statement on access to IL-6-targeting therapies for COVID-19. SITC website. Published March 24, 2020. Accessed March 31, 2020.

2. Genentech Announces FDA Approval of Clinical Trial for Actemra to Treat Hospitalized Patients with Severe COVID-19 Pneumonia [news release]. San Francisco, CA. Published March 23, 2020. Accessed March 31, 2020.