Alexion announced positive top line results in the Phase 3 study of Ultomiris (ravulizumab-cwvz), the long-acting C5 complement inhibitor, met its primary objective in complement inhibitor-naïve patients with atypical hemolytic uremic syndrome (aHUS). In the initial 26 week treatment period, 53.6% of patients (95% CI [39.6%, 67.5%]) 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.

Atypical hemolytic uremic syndrome is a chronic, progressive and debilitating ultra-rare disease that affects both children and adults and can lead to potentially irreversible damage to kidneys and other vital organs, sudden or progressive kidney failure (requiring dialysis or transplant) and premature death.

The primary endpoint of complete TMA response was defined by hematologic normalization and improved kidney function. Treatment with Ultomiris resulted in:

  • Reduced thrombocytopenia, as measured by normalization in platelet count, in 83.9% of patients (95% CI [73.4%, 94.4%]),
  • Reduced hemolysis (the destruction of red blood cells), as measured by normalization in lactate dehydrogenase (LDH) level, in 76.8% of patients (95% CI [64.8%, 88.7%]) and
  • Improved kidney function, as measured by ≥ 25% improvement in serum creatinine level from baseline, in 58.9%this  of patients (95% CI [45.2%, 72.7%]). 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 paroxysmal nocturnal hemoglobinuria (PNH).

“We are very pleased with these data, which demonstrate that Ultomiris can provide clinically meaningful benefits to patients with aHUS,” said John Orloff, MD, Executive Vice President and Head of Research & 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. We are preparing regulatory submissions for Ultomiris in aHUS in the U.S., European Union and Japan as quickly as possible.”

Atypical HUS is a severe and chronic ultra-rare disease that can cause progressive damage to vital organs, predominantly the kidneys, leading to kidney failure and premature death. The disease is characterized by TMA (inflammation and blood clotting in small blood vessels throughout the body) that is mediated by chronic, uncontrolled activation of the complement system.

“If left untreated, many patients progress to end-stage renal disease or die during the first clinical manifestations of aHUS or in the first year following these manifestations despite supportive care,” said Spero Cataland, MD, hematologist at Ohio State University Wexner Medical Center and an investigator in the study. “I am very excited about these data and the potential for an effective new treatment option that can provide hematologic normalization and improved kidney function, including the potential to stop dialysis, when administered every eight weeks.”

The company’s press release can be found here.

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