Alexion Pharmaceuticals said it plans to initiate a phase 3 study of Ultomiris (ravulizumab-cwvz) in adults with COVID-19 who are hospitalized with severe pneumonia or acute respiratory distress syndrome. The C5 complement inhibitor is currently approved in the US, Europe and Japan for adults with paroxysmal nocturnal haemoglobinuria, and in the US for atypical haemolytic uraemic syndrome to inhibit complement-mediated thrombotic microangiopathy in both adult and paediatric patients.
Alexion explained that published preclinical data suggest inhibition of terminal complement can lower cytokine and chemokine levels, and also significantly reduce lung inflammation and pathology in animal models of viral pneumonia. The company also pointed to “promising” preliminary clinical evidence from patients who have accessed another of its terminal complement inhibitors, Soliris (eculizumab), via a compassionate-use program, “which suggests that complement inhibition may improve coronaviral-mediated lung injury.”
Beginning in May, the randomized study is expected to enroll about 270 patients across countries with high numbers of diagnosed cases, and will evaluate Ultomiris versus best supportive care. The primary endpoint is survival at day 29, while secondary goals will assess the need for mechanical ventilation, oxygenation, duration of stay in the intensive care unit and hospitalization, as well as safety. Alexion said the decision to move ahead with the trial follows the FDA’s review and acceptance of the company’s investigational new drug application for Ultomiris for severe COVID-19.
“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,” Alexion stated. “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, [we believe] the outcomes reported to date warrant conducting a controlled clinical programme…with Ultomiris,” it added. The company also noted that the treatment can be manufactured at a higher capacity, “providing the opportunity to better meet future supply demands.”
Meanwhile, Alexion has opened emergency expanded access programs in the US and France for Soliris in severe COVID-19 pneumonia, adding it remains committed to supplying its medicines to patients for currently approved indications.