EUSA Pharma, a global biopharmaceutical company focused on oncology and rare disease, received the approval from the U.S. Food & Drug Administration (FDA) for a randomized, double-blind, placebo-controlled Phase 3 clinical trial to test intravenous siltuximab plus standard of care in hospitalized patients with COVID-19 associated Acute Respiratory Distress Syndrome (ARDS).
The multicentre trial will aim to enrol approximately 400 patients with viral ARDS and elevated serum levels of IL-6. The primary objective is to evaluate all-cause mortality at 28 days with the addition of siltuximab to standard of care, compared to placebo plus standard of care, EUSA said in the press release. Secondary objectives include: time to 7-category ordinal scale of clinical status improvement, ventilator-free days within 28 days, organ failure-free days, intensive care unit length of stay, hospital length of stay, lung function and radiographic improvement.
Siltuximab is a monoclonal antibody that directly neutralizes interleukin (IL)-6, an inflammatory cytokine detected at elevated levels in multiple inflammatory conditions, including COVID-19. It specifically binds to IL-6, thereby inactivating IL-6 induced signalling.
Lee Morley, Chief Executive Officer, EUSA Pharma, said in a press release that has been shown that COVID-19 associated ARDS may exhibit features of systemic hyperinflammation, resulting from excessive cytokine production – the so-called ‘cytokine storm’ – with IL-6 recognized as a key driver of this severe condition.
Morley said that treatment approaches neutralizing IL-6 could therefore play a key role in mitigating further detrimental inflammation and progression to respiratory failure, which can be fatal.
“We thank the FDA for recognizing the importance of this clinical trial and the quick approval we received. Our plan now is to initiate the study as quickly as possible with the hope of seeing improved clinical outcomes in these critically ill patients,” Morley said.
EUSA noted that, to date, several independent clinical trials have begun globally to explore the safety and efficacy of siltuximab for the treatment of severe COVID-19 patients. However, the newly approved confirmatory clinical trial is vital because these findings require validation in a well-controlled randomized study and there is limited published data on the safety and efficacy of siltuximab in COVID-19, EULA said.
EUSA has also reminded that siltuximab is also not yet FDA-approved for complications associated with COVID-19.
Sylvant is an IL-6 targeted monoclonal antibody approved by the FDA and the European Medicines Agency (EMA) as well as regulatory bodies 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). EUSA Pharma has exclusive rights to Sylvant globally. EUSA Pharma has granted BeiGene, Ltd., exclusive development and commercialization rights to Sylvant in Greater China.