Alexion Pharmaceuticals, Inc., a bio-pharmaceutical company focused on serving patients with severe and ultra-rare disorders, announced that the company has submitted marketing applications to the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for Soliris (eculizumab) as a treatment for patients with atypical Haemolytic Uremic Syndrome (aHUS).
Both the US and EU filings include the positive data from the two 26-week phase II studies of Soliris as a treatment for adult and adolescent patients with aHUS. Preliminary data from these two studies were presented at the American Society of Nephrology (ASN) annual meeting in November 2010. Primary endpoints in both studies were achieved with statistical significance. aHUS is an ultra-rare, chronic and life-threatening disease in which uncontrolled complement activation causes blood clots in small blood vessels throughout the body (thrombotic micro-angiopathy, or TMA) leading to kidney failure, stroke, heart attack and death.
“The US and EU regulatory submissions put us one step closer toward accomplishing our goal to transform the lives of patients suffering with aHUS,” said Leonard Bell, MD, chief executive officer of Alexion. “We recognize that patients with aHUS, a life-threatening and ultra-rare disorder, lack adequate treatment options, and we look forward to working with regulatory authorities as they review our applications.”
aHUS is a chronic, ultra-rare disease characterized by Thrombotic Micro-Angiopathy (TMA), the formation of blood clots in small blood vessels throughout the body, causing a reduction in platelet count and life-threatening damage to the kidney, brain, heart and other vital organs. Approximately 60 per cent of patients with aHUS require dialysis or a kidney transplant or die within a year of diagnosis. The majority of patients with aHUS who receive a kidney transplant experience severe complications of the disease, and more than 90 per cent of these patients experience failure of the donor kidney.
aHUS is a progressive disease caused by life-long uncontrolled activation of the complement system due to deficiencies in complement regulatory genes. With genetic deficiency of naturally occurring complement inhibitors, patients experience chronic uncontrolled activation of the complement system, causing ongoing inflammation and blood clots in vital organs. In patients with aHUS, uncontrolled complement activation results in an ongoing risk of sudden and catastrophic life-threatening complications.
Soliris is a first-in-class terminal complement inhibitor developed from the laboratory through regulatory approval and commercialization by Alexion. It has been approved in the US, European Union, Japan and other territories as the first treatment for patients with PNH, a debilitating, ultra-rare and life-threatening blood disorder defined by chronic uncontrolled complement activation which causes chronic red blood cell destruction (haemolysis), leading to blood clots, organ failure, and shortened survival. Prior to these approvals, there were no therapies specifically available for the treatment of patients with PNH. Soliris (eculizumab) is not approved for the treatment of aHUS or other indications other than PNH.
Soliris is generally well tolerated in patients with PNH. The most frequent adverse events observed in clinical studies of patients with PNH were headache, nasopharyngitis (runny nose), back pain and nausea. Treatment with Soliris should not alter anticoagulant management because the effect of withdrawal of anticoagulant therapy during Soliris treatment has not been established.
The US product label for Soliris also includes a boxed warning: “Soliris increases the risk of meningococcal infections. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early. Vaccinate patients with a meningococcal vaccine at least two weeks prior to receiving the first dose of Soliris; re-vaccinate according to current medical guidelines for vaccine use. Monitor patients for early signs of meningococcal infections, evaluate immediately if infection is suspected, and treat with antibiotics if necessary.” During PNH clinical studies, two out of 196 vaccinated PNH patients treated with Soliris experienced a serious meningococcal infection. Prior to beginning Soliris therapy, all patients and their prescribing physicians are encouraged to enroll in the PNH Registry, which is part of a special risk-management program that involves initial and continuing education and long-term monitoring for detection of new safety findings.