Alexion's Soliris Phase 2 clinical study for aHUS meets primary, secondary endpoints

Alexion Pharmaceuticals, Inc. (Nasdaq: ALXN) announced today 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 today 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.

“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.”

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.

Patients Resistant to Plasma Therapy

In an oral presentation today, 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.

Improvement in Platelet Count: A Measure of TMA Reduction

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>

Improvement in Kidney Function

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.

Improvement in Quality of Life Measures

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.6

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."

Patients on Plasma Therapy Chronically

In a poster session yesterday, 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.7 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, M.D., Ph.D., study investigator and associate professor of hematology at Radboud University Medical Center in the Netherlands. "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, M.D., 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."

Pediatric Study

Alexion has commenced a Phase 2, open-label, single-arm, multi-center study of eculizumab in pediatric patients with aHUS in the United States, European Union and Canada. Information about the trial is posted to, Identifier Number NCT01193348. Physicians and families who are interested in participating in this clinical trial can learn more by contacting Alexion by e-mail at [email protected], or by visiting the Alexion website at and clicking on the clinical trials link.


Alexion Pharmaceuticals, Inc.


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