An Anti-CD6 Monoclonal Antibody (Itolizumab) Reduces Circulating IL-6 in Severe Covid-19 Elderly Patients

Abstract

Background: Since the COVID-19 outbreak an unprecedented challenge for healthcare systems around the world has been placed. In Cuba, the first case of COVID-19 was reported on March 11. Elderly with multiple comorbidities have been the most risky population. Although most patients present a mild to moderate disease, some have developed severe symptoms. One of the possible mechanisms underlying rapid disease progression is a cytokine storm, in which interleukin (IL) -6 seems to be a major mediator. Itolizumabis a humanized recombinant anti-CD6 monoclonal antibody(MAb), with the ability of reducingserum interferon gamma(INF-γ), tumournecrosis factor alpha(TNFα) and IL-6. Based on these previous results in patients with psoriasis and rheumatoid arthritis, an expanded access clinical trial was approved by the Cuban regulatory agency for COVID-19 critically, severely and moderately ill patients. Results: We show here a short kinetic of IL-6 serum concentration in the first 24 COVID-19 patients treated with itolizumab. Most of patients were elderly with multiple comorbidities.We found that with one itolizumabdose, the circulating IL-6 decreased in critically and severely ill patients, whereas in moderately ill patients the values didn’trise as compared to theirlow baseline levels.Conclusion: These findings suggest that itolizumabcould be an attractive therapeutic option to decrease the negative outcome of the cytokine storm in COVID-19 patients.Trial registration: CECMED IIC RD-EC 179, RPCEC00000311. Registered 4May 2020 - Retrospectively registered, http://rpcec.sld.cu/ensayos/RPCEC00000311-Sp or http://rpcec.sld.cu/trials/RPCEC00000311-En

Approval of Itolizumab for COVID-19: A Premature Decision or Need of The Hour?

“…Two studies on preprint servers are available presently; both are from the same Cuban trial (RPCEC00000311). One study shows that a single dose of itolizumab decreased the serum IL-6 levels after 48 h of administration in 24 moderate to critically ill elderly COVID-19 patients [22]. In another study, the authors concluded that in 19 moderately ill elderly COVID-19 patients, itolizumab treatment was associated with a significantly reduced risk of admission to ICU and a 10 times lower risk of death [23].…”

“…The potential utility of itolizumab in COVID-19, based on its mechanism of action, led to expanded access use and conduct of a trial in Cuba, retrospectively registered with the Cuban regulatory agency (Center for the State Control of Medicines, Equipment and Medical Devices, CECMED) in May 2020. This trial recruited patients with critical and severe illness, and moderately ill patients with very high risk of developing severe symptoms [6]. Encouraged by the initial promising results with the first few patients seen in this index trial, regulatory permission was received to repurpose the drug for COVID-19 in India.…”

The global response to the COVID-19 pandemic: how have immunology societies contributed?

“…Second, patients with COVID-19 were treated with immunotherapeutics developed in Cuba, including human recombinant interferon alfa-2b 41 , later combined with interferon-γ, a humanized recombinant monoclonal antibody to CD6 (reF. 42 ) and an immunomodulatory peptide, CIGB-258, which is derived from heat shock protein 60 (HSP60) 43 . Third, preventive strategies were introduced for vulnerable populations that used Cuban products to stimulate trained immunity or immunocompetence (Biomodulin T) 40 .…”

Current Approaches to COVID-19: Therapy and Prevention

“…It could be an attractive therapeutic option to control the cytokine storm in patients with COVID19. 74 Itolizumab is under phase II clinical study in India for the management of moderate to severe ARDS in patients with COVID-19 disease (CTRI Identifier: CTRI/2020/05/024959). 75…”