The study is expected to enroll approximately 270 patients across countries with high numbers of diagnosed cases, beginning in May, and will evaluate the impact of ULTOMIRIS, a biologic medicine, on survival, duration of mechanical ventilation, and hospital stay compared to best supportive care. This follows the U.S. Food and Drug Administration’s (FDA) rapid review and acceptance of Alexion’s investigational new drug (IND) application for ULTOMIRIS for severe COVID-19.
“Alexion has been in close contact with physicians and global health authorities in an effort to rapidly evaluate the potential of C5 inhibition in treating patients with severe COVID-19,” said John Orloff, M.D., Executive Vice President and Head of Research & Development at Alexion. “Based on early anecdotal information available from compassionate use cases in multiple countries, we are launching a controlled clinical trial to evaluate the potential of ULTOMIRIS in mitigating the severe pneumonia and lung injury caused by the virus. As we move quickly to initiate this program, we also remain committed to serving the patients who currently rely on our medicines and providing continuous supply to these patients.”
The decision to begin this trial is based on a) published preclinical data suggesting that inhibition of terminal complement can lower cytokine and chemokine levels and significantly reduce lung inflammation and pathology in animal models of viral pneumoniai, and b) elevated complement biomarkers and promising preliminary clinical evidence from patients who have accessed SOLIRIS® (eculizumab) through our compassionate use program, which suggests that complement inhibition may improve coronaviral-mediated lung injury.
Independent investigators have expressed interest in studying the potential of C5 inhibition in severe COVID-19 pneumonia, and we are aware of several ongoing or planned independent studies and anecdotal results from the use of our C5 inhibitors in patients with COVID-19. While these healthcare professionals continue to aggregate data regarding the potential of terminal complement inhibition in COVID-19 pneumonia from the approximately 100 patients who have been treated so far, Alexion believes that the outcomes reported to date warrant conducting a controlled clinical program to explore the impact of C5 inhibition with ULTOMIRIS and establish clinical evidence supporting the role of terminal complement in coronaviral pneumonia. We believe ULTOMIRIS represents the future of C5 inhibition, with its weight-based dosing, reduced burden on hospital systems due to less frequent dosing and it can be manufactured at a higher capacity, providing the opportunity to better meet future supply demands.
he Phase 3 open-label, randomized, controlled study is designed to evaluate the safety and efficacy of ULTOMIRIS in approximately 270 adults hospitalized with COVID-19 and severe pneumonia, acute lung injury or acute respiratory distress syndrome (ARDS). Study participants will be randomized 2:1 to receive ULTOMIRIS or best supportive care. The primary endpoint is survival at Day 29. Secondary endpoints will assess the need for mechanical ventilation, oxygenation, duration of ICU stay and hospitalization, and safety, among others.
Patients in the ULTOMIRIS arm will receive a weight-based loading dose of ULTOMIRIS on Day 1 (2400mg for patients weighing 40-60kg, 2700mg for 60-100kg, or 3000mg for ≥100kg). Follow-up dosing on Days 5, 10 and 15 will also be weight-based; patients weighing 40 to 60kg will receive 600mg of ULTOMIRIS and patients weighing 60kg or more will receive 900mg of ULTOMIRIS. All patients will continue to receive medications, therapies, and interventions per standard hospital treatment protocols for the duration of the study. Following the 4-week treatment period, there will be safety follow-up monitoring for three months.
ULTOMIRIS® (ravulizumab-cwvz) is the first and only long-acting C5 complement inhibitor. The medication works by inhibiting the C5 protein in the terminal complement cascade, a part of the body’s immune system. When activated in an uncontrolled manner, the complement cascade over-responds, leading the body to attack its own healthy cells. For currently approved indications, ULTOMIRIS is administered intravenously every eight weeks or every four weeks for pediatric patients less than 20 kg, following a loading dose. ULTOMIRIS is approved in the United States (U.S.), European Union (EU) and Japan as a treatment for adults with paroxysmal nocturnal hemoglobinuria (PNH) and in the U.S. for atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy (TMA) in adult and pediatric (one month of age and older) patients.
Source: Company Press Release