Alexion Pharmaceuticals, Inc. announced that a Phase 2 clinical study investigating Soliris (eculizumab) as a treatment for patients with atypical Hemolytic Uremic Syndrome (aHUS) who are resistant to plasma therapy met primary and key secondary endpoints with high levels of statistical and clinical significance, according to results presented at the American Society of Nephrology (ASN) annual meeting in Denver. The new data are consistent with an earlier interim analysis contained in the abstract of today’s presentation and published online by ASN on October 20, 2010. 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 analysis 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 anemia, headache, diarrhea 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, M.D., 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.”
Date: November 20, 2010
Source: Alexion Pharmaceuticals, Inc.
Filed Under: Drug Discovery