Alexion Pharmaceuticals, Inc. announced that a phase 2 clinical study investigating Soliris (eculizumab) as a treatment for patients with atypical Haemolytic Uremic Syndrome (aHUS) who are resistant to plasma therapy met primary and key secondary endpoints with high levels of statistical and clinical significance. Soliris is a first-in-class terminal complement inhibitor discovered and developed by Alexion.

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 microangiopathy, or TMA) leading to kidney failure, stroke, heart attack and death because aHUS is a genetic disease, patients have a life-long risk of sudden and severe complications of uncontrolled complement activation. Approximately 60% of patients with aHUS require dialysis, undergo a kidney transplant, or die within one year of diagnosis.

In an oral presentation, researchers reported final data from a phase 2 study of eculizumab in patients with aHUS who were resistant or intolerant to plasma therapy. This included 17 adolescent and adult patients who received eculizumab therapy for 26 weeks. The prospective primary endpoint was the change in platelet count from baseline, a measure of TMA, at 26 weeks. Key prospective secondary endpoints included TMA event-free status (defined as at least 12 consecutive weeks of stable or increasing platelet counts, absence of plasma therapy, and no new dialysis), improvements in Chronic Kidney Disease (CKD) stage, and change in quality of life.

The primary endpoint of the study, change in platelet count, increased significantly through 26 weeks of treatment compared to baseline (p<0.0001) and was increased 96 ± 21 x109/L at 26 weeks of treatment with eculizumab. Researchers reported that following the first infusion of eculizumab, platelet count increased significantly at Day 7 (p=0.02). A key secondary endpoint, TMA event-free status, was achieved in 88% of patients (15 of 17; 95% CI 64-100).

Researchers reported significant improvement in kidney function with sustained eculizumab therapy over the 26-week dosing period. Estimated Glomerular Filtration Rate (eGFR), a standard measure of kidney function, increased sufficiently to result in an improvement of at least one stage in CKD in 65% of patients (11 of 17, 95% CI 33-82), and eGFR increased less than one CKD stage in four additional patients. Of the seven patients who received dialysis before entering the study, five became dialysis-free following treatment with eculizumab and remained so for the entire 26 weeks.

Quality of life as measured by the summary index of the EuroQol 5D improved significantly through 26 weeks. The improvement was highly statistically significant compared to baseline (p<0.0001) and was improved 0.33 ± 0.09 at 26 weeks which was more than five times the level generally considered to be a clinically meaningful change.

All reported study results were similar for patients with and without complement regulatory protein mutations or auto-antibodies. Eculizumab was well tolerated in the study, and all patients remain alive. There were no cases of meningococcal infection in the trial. The most frequent adverse events were anaemia, headache, diarrhoea and vomiting. Two patients withdrew from the study; one patient was withdrawn after it was subsequently determined that the patient met an exclusion criterion and one patient withdrew from the study due to an adverse event deemed unrelated to eculizumab.

“These ground-breaking results show that eculizumab significantly increased platelets and reduced the life-threatening blood clot process that caused severe damage to the kidney and other organs in these patients with aHUS,” said Christophe Legendre, MD, a study investigator and professor of nephrology at University Rene Descartes-Hôpital Necker in Paris. “The stabilization and improvement of kidney function observed in this study is particularly meaningful because these patients are resistant to plasma therapy, one of the current management strategies for aHUS” he added.

In a poster session researchers presented interim results from a separate Phase 2 study of 20 adult and adolescent patients with aHUS who were receiving plasma therapy chronically prior to starting treatment with eculizumab. These interim results were the same as previously reported. The prospective primary endpoint in this study was TMA event-free status, which was achieved by a significant 87% of patients in the interim 12-week analysis of 15 patients (13 of 15; 95% CI 60-98). The analysis also met a key prospective secondary endpoint: none of the patients treated with eculizumab required TMA intervention.

“aHUS is a devastating disease and patients are chronically at risk for disease progression including sudden onset of stroke, heart attack, kidney failure and death, even if they are treated frequently with currently available interventions,” said Petra Muus, MD, PhD, study investigator and associate professor of haematology at Radboud University Medical Centre in the Netherlands.  He further added “These findings show that studied patients demonstrated an immediate response and sustained efficacy with eculizumab, giving the aHUS community hope for reducing the need for new dialysis and plasma therapy.”

Eculizumab appeared to be well tolerated in the study. The most frequent adverse events were diarrhea, nausea, headache and hypertension (all mild to moderate). “The results from these Phase 2 studies suggest that it may be possible to change the course of aHUS by targeting chronic uncontrolled complement activation,” said Leonard Bell, MD, Chief Executive Officer of Alexion. “The significant increase in platelet count, reduction in TMA, restored kidney function, and improved quality of life reported today indicates that eculizumab may have the potential to transform the lives of patients with this devastating disease and their families. We continue to advance this important program.”

Alexion has commenced a Phase 2, open-label, single-arm, multi-centre study of eculizumab in paediatric patients with aHUS in the United States, European Union and Canada.

aHUS is a chronic, ultra-rare disease characterized by Thrombotic Microangiopathy (TMA), the formation of blood clots in small blood vessels throughout the body, causing a reduction in platelet count (thrombocytopenia) 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, despite currently available care. 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 uncontrolled activation of the complement system due to genetic deficiency in complement regulatory genes. With genetic deficiency of naturally occurring complement inhibitors, patients experience life-long 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 not approved for the treatment of patients with aHUS and is being provided to patients in clinical studies on an investigational basis. It has been approved by the healthcare authorities in the United States, European Union, Japan and other countries as the first treatment for patients with Paroxysmal Nocturnal Hemoglobinuria (PNH), a rare, debilitating and life-threatening blood disorder defined by hemolysis, or the destruction of red blood cells. Prior to these approvals, there was no therapy specifically available for the treatment of PNH. It is a first-in-class terminal complement inhibitor developed from the laboratory through regulatory approval and commercialization by Alexion.

Patients with PNH in more than 20 countries now have access to Soliris therapy through national or private healthcare providers. As the first terminal complement inhibitor to be approved in countries around the world for any indication, Soliris represents a long-sought breakthrough in medical innovation. Alexion's innovative approach to complement inhibition has received some of the pharmaceutical industry's highest honors: the 2008 Prix Galien USA Award for Best Biotechnology Product with broad implications for future biomedical research and the 2009 Prix Galien France Award in the category of Drugs for Rare Diseases.

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.



Alexion Pharmaceuticals, Inc. is a biopharmaceutical company working to develop and deliver life-changing drug therapies for patients with serious and life-threatening medical conditions.

Soliris is Alexion's first marketed product. Alexion is evaluating other potential indications for Soliris as well as other formulations of eculizumab for additional clinical indications, and is pursuing development of other antibody product candidates in early stages of development.