Alexion Reports Positive Results for Ultomiris in aHUS, Moving to File for Approval

January 28, 2019

Rare Daily Staff

Alexion Pharmaceuticals reported that the company’s late-stage study of Ultomiris, its long-acting C5 complement inhibitor, met its primary endpoint in complement inhibitor-naïve patients with atypical hemolytic uremic syndrome, a severe and chronic ultra-rare disease.

Atypical hemolytic uremic syndrome (aHUS) can cause progressive damage to vital organs, predominantly the kidneys, leading to kidney failure and premature death. The disease is characterized by inflammation and blood clotting in small blood vessels throughout the body—a condition known as thrombotic microangiopathy (TMA)—that is mediated by chronic, uncontrolled activation of the complement system.

Ultomiris is the first and only long-acting C5 inhibitor administered every eight weeks that works by inhibiting the C5 protein in the terminal complement cascade, a part of the body’s immune system. The terminal complement cascade, when activated in an uncontrolled manner, plays a role in severe ultra-rare disorders like aHUS, paroxysmal nocturnal hemoglobinuria (PNH), and anti-acetylcholine receptor (AchR) antibody-positive myasthenia gravis (MG). Ultomiris is approved in the United States as a treatment for adults with PNH.

Regulators in the United States and Europe have granted Alexion Orphan Drug designation for Ultomiris for the treatment of patients with PNH. It also has Orphan Drug designation in the United States for the subcutaneous treatment of patients with aHUS.

In the initial 26-week treatment period, 53.6 percent of patients demonstrated complete thrombotic microangiopathy (TMA) response. Ultomiris provided immediate and complete inhibition of the complement C5 protein that was sustained over the entire eight-week dosing interval.

The primary endpoint of complete TMA response was defined by hematologic normalization and improved kidney function.

Treatment with Ultomiris resulted in a normalization in platelet count (83.9 percent of patients), reduced destruction of red blood cells as measured by normalization in lactate dehydrogenase level (76.8 percent of patients), and improved kidney function, as measured by ≥ 25 percent improvement in serum creatinine level from baseline (58.9 percent of patients). For patients on dialysis at enrollment, baseline was established after they had come off dialysis.

To achieve complete TMA response, patients had to meet all three criteria at the same time at least once. In addition, each of the criteria had to be met for at least 28 consecutive days.

The safety profile was consistent with that observed in two large phase 3 studies in patients with PNH.

“We are very pleased with these data, which demonstrate that Ultomiris can provide clinically meaningful benefits to patients with aHUS,” said John Orloff, executive vice president and head of research and development at Alexion. “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.”

Orloff said it is preparing regulatory submissions for Ultomiris in aHUS in the United States, European Union, and Japan “as quickly as possible.”


January 28, 2019
Photo: John Orloff, executive vice president of Alexion Pharmaceuticals

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