An update on the Siltuximab clinical study brings interim analysis data for Siltuximab-Treated COVID-19.
EUSA Pharma has announced the initial preliminary findings from the Papa Giovanni XXIII Hospital sponsored SISCO (Siltuximab In Serious COVID-19) Study, based on a pre-planned data analysis on 24 March 2020.
Siltuximab is an interleukin (IL)-6 targeted monoclonal antibody approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) as well as in a number of other jurisdictions worldwide for the treatment of patients with multicentric Castleman disease (MCD) who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative (also known as idiopathic MCD; iMCD). Siltuximab is under investigation for COVID-19 patients who have developed serious respiratory complications, the leading cause of morbidity and mortality.
The interim data for Siltuximab-Treated COVID-19, presented from the first 21 patients treated with siltuximab and followed for up to 7 days, show that one-third (33%, n=7) of patients experienced a clinical improvement with a reduced need for oxygen support and 43% (n=9) of patients saw their condition stabilise, indicated by no clinically relevant changes. Combined, this means that over three-quarters of patients treated with siltuximab (76%, n=16) had either stable or improved disease at this interim analysis. A worsening of the disease was seen in 3 (14%) patients whilst 1 (5%) patient died and 1 (5%) experienced a cerebrovascular event.
Furthermore, C-Reactive Protein (CRP) levels, a marker of systemic inflammation, declined from baseline through to Day 5 following treatment with siltuximab in all patients with sufficient recorded values (100%, 16/16). This level of reduction was maintained in those patients (100%, 16/16) 7 days after receiving treatment with siltuximab. Reduction in CRP is considered a robust surrogate for indicating the efficacy of IL-6 inhibition.
The majority (90%, 19/21) of patients presented with fever at baseline, 13/21 (62%) with a dry cough and 15/21 (71%) with dyspnoea (shortness of breath). Partial pressure of arterial oxygen (PaO2) to percentage of inspired oxygen (FiO2), otherwise known as the P/F ratio or lung function, and IL-6 had out of normal ranges at baseline in the majority of patients with a median P/F ratio of 127 (excluding those >300 and indicating Acute Respiratory Distress Syndrome [ARDS]3) and median peripheral IL-6 levels of 140 pg/mL (range 113-239 pg/mL). Serum CRP was elevated in all patients at baseline with a median of 23 mg/dL (range 10-43 mg/dL).
A manuscript is in preparation for submission to a leading medical journal, and the pre-print summary has been deposited and will be available via medRxiv.org imminently.
Professor Alessandro Rambaldi, MD, PhD, Papa Giovanni XXIII Hospital, Bergamo, Italy, Study Sponsor-Investigator and Director of the Hematology Unit and Department of Oncology and Hematology, said: “The team at Papa Giovanni XXIII Hospital are pleased to share these preliminary observational data. Whilst we are yet to identify and analyse the control group of patients, these initial data in siltuximab-treated patients provide vital information to guide decisions regarding appropriate use of siltuximab in both the real-world and new COVID-19 studies as we continue to investigate the role IL-6 blockade can play. Importantly, these preliminary uncontrolled data confirm high levels of IL-6 at baseline, with baseline CRP also high but declining with siltuximab treatment, suggesting a role for monoclonal antibodies as a possible therapeutic strategy for this fatal infectious disease. Further data will be made available on remaining patients, the case-control analysis and 30 day follow-up of mortality as they become available.”
Lee Morley, Chief Executive Officer, EUSA Pharma, said: “We are very pleased to be able to release these preliminary data from the SISCO Study and hope the findings will help to guide real-world treatment decisions during this critical emergency situation. We look forward to engaging in further studies to research the potential of siltuximab for patients suffering severely with respiratory complications from COVID-19 and making additional data available as soon as possible. We are very grateful to the team at Papa Giovanni XXIII Hospital in Bergamo, Italy, for their extraordinary efforts to undertake the SISCO Study and collate these interim data under extremely difficult circumstances.”
Ergomed is providing clinical development and research services for the study and has been integrally involved in the design and implementation of the study from a clinical and operational perspective.
Dr Miroslav Reljanović, Executive Chairman of Ergomed, said: “We are pleased to see the preliminary data which will help inform the most appropriate use of siltuximab in patients with COVID-19 suffering from serious respiratory complications. We continue to provide clinical development and research services, working closely with the investigators at the Papa Giovanni XXIII Hospital and with EUSA. We look forward to the completion of the study and the insights it might bring for the development of a treatment for COVID-19.”