Boston-based Alexion’s Ultomiris (ravulizumab-cwvz) hit its primary objective in its Phase III study of complement inhibitor-naïve patients with atypical hemolytic uremic syndrome (aHUS).

aHUS is a chronic, progressive and debilitating ultra-rare disease. It affects children and adults and can lead to irreversible kidney damage as well as affecting other vital organs. It can result in sudden and progressive kidney failure and premature death. The disease symptoms include inflammation and the formation of blood clots in small blood vessels throughout the body mediated by uncontrolled activation of part of the immune system called the complement system.

In the trial, 53.6 percent of patients receiving Ultomiris showed complete thrombotic microangiopathy response, giving immediate and complete inhibition of the complement C5 protein. This was sustained over the eight-week dosing interval.

The primary endpoint of complete TMA response was defined by hematologic normalization and improved kidney function. Those receiving the drug had reduced thrombocytopenia, reduced destruction of red blood cells, and improved kidney function.

TMA response was defined within the study as meeting all three criteria at the same time at least once and that criteria had to be hit for at least 28 consecutive days.

“We are very pleased with these data, which demonstrate that Ultomiris can provide clinically meaningful benefits to patients with aHUS,” stated John Orloff, Alexion’s executive vice president and Head of Research & Development. “The results met the high bar of complete TMA response, defined by hematologic normalization and improved kidney function, and provide confidence that Ultomiris has the potential to become the new standard of care for patients with aHUS. We are preparing regulatory submissions for Ultomiris in aHUS in the U.S., European Union and Japan as quickly as possible.”

A Phase III trial of the drug in children and adolescents with aHUS is ongoing.

Ultomiris is a longer-acting vision of the Alexion drug, Soliris. Alexion is in the process of moving patients from Soliris to Ultomiris as a way of fighting competition, including from companies working to develop biosimilars to Soliris.

Currently, Ultomiris is approved by the U.S. Food and Drug Administration (FDA) for adults with paroxysmal nocturnal hemoglobinuria (PNH), dosed every eight weeks after the initial loading dose. PNH is a rare, acquired, life-threatening disease of the blood noted by destruction of red blood cells by the complement system. 

Soliris is approved for PNH, aHUS and anti-AchR+ generalized Myasthenia Gravis. The latter disease is an autoimmune disease marked by the uncontrolled production of anti-AchR antibodies.

In the second quarter of 2018, Soliris brought in $898.2 million, compared to $813.3 million in the same period the year before. For the first half, Soliris generated $1.596 billion, with $605.9 million coming from the U.S.

The FDA approved Ultomiris on December 21, 2018, for PNH. At the time, Richard Pazdur, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, stated, “The approval of Ultomiris will change the way that patients with PNH are treated. Prior to this approval, the only approved therapy for PNH required treatment every two weeks, which can be burdensome for patients and their families. Ultomiris uses a novel formulation so patients only need treatment every eight weeks, without compromising efficacy.”



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