In an editorial, researchers from the Society for Immunotherapy of Cancer (SITC) suggested that though definitive data showing that IL-6 receptor blockade benefits patients with COVID-19 induced pneumonitis are currently lacking, an effort should be made to maximize the availability of anti-IL-6 agents on a compassionate basis to treat hospitalized critically ill patients infected with COVID-19.
Further, they suggested that considerations should be given to focus efforts on rapidly expanding the ability of clinicians and clinical investigators to access investigational anti-IL-6 agents, particularly for agents where phase I and/or phase II studies have been completed and acceptable safety was demonstrated.
“Even if the primary impact of a single dose of these drugs is to accelerate recovery and get patients off ventilator support and out of the ICU more rapidly, this could significantly decompress our severely over-burdened healthcare systems,” the authors wrote. “A simple compassionate use protocol could be assembled from existing templates, and all efforts should be made for emergency approval of the use of IL-6 receptor blocking antibodies by local institutional review boards within 24 hours of the request being made.”
The use of IL-6 or IL-6 receptor blocking antibodies like tocilizumab (Actemra), sarilumab (Kevzara), and siltuximab (Sylvant) that are FDA approved for various conditions including rheumatologic disease and the lymphoproliferative disorder Castleman’s syndrome could potentially be used to treated hospitalized critically ill patients with COVID-19-induced hypoxia, according to the researchers.
Tocilizumab specifically has data from the frontlines of the pandemic that indicate that the agent might offer lifesaving benefit for patients with COVID-19 in respiratory distress. Currently, tocilizumab is FDA approved to manage cytokine release syndrome (CRS) in patients receiving CAR T-cell therapy.
However, tocilizumab has been shown to reduce toxicity in patients treated with immune checkpoint inhibitors who were steroid refractory and has been added to ipilimumab (Yervoy) and nivolumab (Opdivo) in an ongoing phase II study. In Castleman’s disease, the agent has been shown to reduce viral loads. Moreover, tocilizumab is being explored as a possible supportive care measure for the management of CRS in patients with cancer treated with several CD3-based bispecific molecules.
The researchers suggested straightforward parameters for the implementation of anti-IL-6 agents, including that complete blood counts and differentials, serum LDH, ferritin, CRP, and IL-6 be recorded in treated patients, that serum be retained for future evaluation, and simple clinical parameters be assessed including time in ICU, days of hospitalization, and pulmonary parameters including FEV1, Fi02, PaO2/FiO2 ratio and oxygen need be recorded.
“Additionally, consideration should be given by pharma and biotech to redirect the use of facilities and increase personnel involved in drug manufacturing and those serving as liaisons to the frontlines to facilitate drug availability,” the authors wrote.
Investigators in Italy and China who have used tocilizumab to treat patients infected with COVID-19 at doses comparable to those used for the management of CRS have reported rapid improvement in both intubated and non-intubated patients. In these reports, the expedited administration of anti-IL-6R therapy for patients in acute respiratory distress has been essential.
A recent study protocol to evaluate the efficacy of tocilizumab in COVID-19 induced pneumonitis was able to accrue over 300 patients worldwide in less than 24 hours. Genentech also indicated that they will provide 10,000 vials of the agent to the US Strategic National Stockpile. 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.
In the US, a trial of sarilumab in the COVID-19 setting remains ongoing.
“Sponsors, investigators, and regulators have moved with unprecedented speed and collaboration to initiate protocols to formally study the safety and efficacy of antiviral agents and vaccines, as well as various anti-IL-6 antibodies in patients with COVID-19,” the authors wrote. “Extraordinary times call for extraordinary measures, and SITC calls on all involved, including pharmaceutical sponsors, health authorities and IRBs, to continue to move swiftly and creatively to respond and unite in removing barriers to provide our patients with care.”
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. sitcancer.org/research/covid-19-resources/il-6-editorial. Accessed March 27, 2020.