Phase III success for Ultomiris in complement inhibitor-naïve patients with atypical hemolytic uremic syndrome . Alexion Pharma

Alexion Pharmaceuticals, Inc. announced that the Phase III study of Ultomiris (ravulizumab-cwvz), the company's 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 percent 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. 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 percent 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 percent of patients (95% CI [64.8%, 88.7%]) and - improved kidney function, as measured by greater than 25 percent improvement in serum creatinine level from baseline, in 58.9 percent 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 III studies in patients with paroxysmal nocturnal hemoglobinuria (PNH).The most frequently observed adverse events in this study were headache, diarrhea and vomiting. The most frequently observed serious adverse events were pneumonia and hypertension. In these critically ill patients, there were four patient deaths, none of which were considered related to treatment with Ultomiris. No case of meningococcal infection was observed. Meningococcal infections are a known risk with terminal complement inhibition. To minimize the risk for patients, specific risk-mitigation plans have been established for Ultomiris, based on plans that have been in place for more than 11 years for Soliris (eculizumab). Detailed results from this Phase III study will be presented at a future medical congress. A Phase III study of Ultomiris in children and adolescents with aHUS is currently ongoing.