Alexion Pharmaceuticals, Inc., a company that is advancing a rare disease pipeline in complement biology, recently issued a series of press releases announcing positive results of a Phase 3 study of Ultomiris™ (Ravulizumab-cwvz) in previously untreated patients with atypical Hemolytic Uremic Syndrome (aHUS)
About Atypical Hemolytic Uremic Syndrome (aHUS)
The symptoms of aHUS, an ultra-rare disease, are acute kidney failure (uremia), low platelet count (thrombocytopenia), and low levels of circulating red blood cells. It is a complex disorder. Genetic, environmental and immunologic factors all play a role in its development.
Although some cases of aHUS may occur for unknown reasons (idiopathic) or be acquired due to autoantibodies, most cases of aHUS are genetic. Chronic complications such as hypertension or kidney failure may develop.
Another symptom is the appearance of blood clots in small blood vessels in the body that may reduce, or even prevent, blood flow to various organs, predominantly the kidneys, leading to kidney failure.
The disease may develop prenatally or even into adulthood. It strikes suddenly, usually after an upper respiratory infection or gastroenteritis.
More details about aHUS are available here.
Ultomiris is an inhibitor of the C5 protein which plays a role in immune system. When activated, the terminal complement cascade, the area of the immune system in which C5 is active, plays a role in many rare disorders, including aHUS. Ultomiris, which is administered at eight-week intervals, is the first and only long-acting C5 inhibitor.
Alexion focuses on the therapeutic areas of hematology, nephrology, neurology and metabolic disorders. The company’s aim is to redefine what it means to live with a rare disease.
Alexion has developed the first and only approved complement inhibitor that treats atypical hemolytic uremic syndrome (aHUS).
The company has announced that it is preparing submissions for Ultomiris in aHUS in the U.S., European Union, and Japan.
About the Ultomiris aHUS-311 Study
The Phase 3 study evaluated the safety and efficacy of Ultomiris. It was conducted in multiple locations with a select group of 56 patients over the age of 18, who had not been previously treated with a complement inhibitor. The study involved a screening period of up to seven days, followed by a 26-week evaluation, plus a two-year extension period which is still ongoing. The drug was administered by intravenous infusion. More information on the Phase 3 study is available here.
Results of the Ultomiris Study
The primary objective of the study was complete thrombotic microangiopathy (TMA) response. The primary endpoint of complete TMA response is defined by improved kidney function and complete hematologic normalization.
Complete and immediate inhibition of the complement C5 protein was sustained throughout the eight-week dosing interval with Ultomiris.
Treatment with Ultomiris also resulted in improved kidney function; it reduced the destruction of red blood cells and increased normalization in platelet count.
Patients were required to meet all three criteria simultaneously for a minimum of 28 days in order to achieve a complete TMA response.
Planning for the Future
Ultomiris has received Orphan Drug Designation for the treatment of patients with aHUS in the U.S.
A Phase 3 clinical study involving complement inhibitor-naive (previously untreated) children and adolescents is currently underway. The study evaluates Ultomiris administered intravenously at eight-week intervals.
Alexion also has plans to start a Phase 3 clinical study of Ultomiris as a possible treatment for aHUS and PNH (paroxysmal nocturnal hemoglobinuria) which is a rare bone marrow failure disorder. The drug will be administered by injection once each week.
Alexion’s aim is to redefine what it means to live with a rare disease.