Alexion Pharmaceuticals, Inc. (Nasdaq: ALXN) today announced the presentation of final data from the two Phase 2 studies of Soliris® (eculizumab) as a treatment for patients with atypical hemolytic uremic syndrome (aHUS): (i) a study in patients who were resistant to plasma exchange/infusion and received eculizumab and (ii) a study in patients who were receiving chronic plasma exchange/infusion followed by late intervention with eculizumab. Consistent with previously announced data, both studies met their primary endpoints and key secondary endpoints with high levels of statistical and clinical significance. Separately, researchers presented for the first time findings from a retrospective clinical study of eculizumab in pediatric patients with aHUS. These three studies were presented at the 16th Congress of the European Hematology Association (EHA) in London.
aHUS is an ultra-rare, genetic, life-long disease in which chronic uncontrolled complement activation causes blood clots in small blood vessels throughout the body (thrombotic microangiopathy, or TMA), leading patients to suffer kidney failure, stroke, heart attack and death. Approximately 60% of patients with aHUS require dialysis, undergo a kidney transplant, or die within one year of diagnosis. Alexion has filed marketing applications with the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for eculizumab, a first-in-class terminal complement inhibitor, as a treatment for patients with aHUS.
"Final data from these pivotal clinical trials suggest that complement inhibition therapy with eculizumab could potentially alter the course of aHUS," said Leonard Bell, M.D., Chief Executive Officer of Alexion. "By considerably reducing TMA, investigators have demonstrated that eculizumab improved kidney function, reduced the need for interventions such as dialysis, and substantially improved quality of life in the studied patients. We continue to work closely with regulatory authorities and the aHUS community with the goal of offering a safe and effective treatment option for patients suffering with this ultra-rare, devastating, and life-threatening disease."
Patients Resistant to Plasma Exchange/Infusion
In a poster session today, researchers presented final data from a Phase 2 study of eculizumab in 17 adult and adolescent patients who were resistant or intolerant to plasma exchange/infusion and received eculizumab. Fifteen patients received eculizumab therapy for 26 weeks; two patients did not complete the study but were included in the analysis. Of note, patients in this study had a median duration of aHUS from diagnosis to screening of 10 months (range: 1-236).
The study met its primary endpoint and key secondary endpoints with high levels of statistical and clinical significance, and findings were consistent with data reported at the 2010 American Society of Nephrology annual meeting. For the primary endpoint, platelet count increased from baseline through week 26 by a point estimate 73×109/L.
With regard to secondary endpoints, 15 patients (88% of the total enrollment and 100% of those analyzed per protocol) achieved TMA event-free status, defined as at least 12 consecutive weeks of stable or increasing platelet counts, absence of plasma exchange/infusion, and no new dialysis. Median TMA intervention (plasma exchange/infusion/dialysis) rate decreased from 0.88 events per patient per day to 0 (p<0.0001). Four out of 5 dialysis patients became dialysis-free, and 10 patients (59%; 95% CI 33-82) had sustained improvement in chronic kidney disease by at least one stage. Eight out of 17 patients (47%; 95% CI 23-82) had increased renal function by at least 15 mL/min/1.73 m2. Improvements in health-related quality of life (HRQoL) were highly statistically significant, with 80% of patients experiencing a clinically meaningful benefit. The mean change in HRQoL from baseline to week 26 of eculizumab treatment was 0.29±0.28 (p<0.002). Eculizumab was well tolerated in the study. The most frequently reported adverse events were headache, anemia and diarrhea (generally mild to moderate in severity). An extension trial continues.
Patients Receiving Chronic Plasma Exchange/Infusion
In another poster presentation today, researchers presented final data from a Phase 2 study of Soliris in aHUS patients who were receiving chronic plasma exchange/infusion. In this 26-week study, 20 patients continued to receive plasma exchange/infusion during an 8-week observation period, and then discontinued plasma exchange/infusion and commenced eculizumab treatment. Of note, patients in this study received late intervention with eculizumab: they had a median duration of aHUS from diagnosis to screening of 48 months (range: 0.66-286), with a long duration of renal insufficiency. In the study, 80% of patients achieved TMA event-free status, the primary endpoint, defined as at least 12 consecutive weeks of stable platelet count, absence of plasma exchange/infusion, and no new dialysis.
Key secondary endpoints were also achieved with high clinical and statistical significance. Platelet count normalization was achieved in 18 out of 20 patients (90%); all patients who had normal platelet count at baseline (17 out of 20) maintained that level after discontinuation of plasma exchange/infusion and commencement of eculizumab treatment. TMA intervention rate (number of plasma exchange/infusion and new dialysis events per patient per day) decreased from a median of 0.23 events per patient per day to zero events (p<0.0001). Seven out of 20 patients (35%, 95% CI 15 - 59) experienced a sustained improvement of at least one stage of chronic kidney disease (CKD). During treatment with eculizumab, all patients (100%) discontinued plasma exchange/infusion and did not require new dialysis.
In addition, treatment with eculizumab significantly improved quality of life, with 73% of patients achieving a clinically meaningful benefit. Mean change from baseline to week 26 was 0.11±0.19 (p<0.002). Eculizumab was well tolerated by patients in the study. The most frequently reported adverse events were diarrhea, headache, hypertension and nausea (generally mild to moderate in severity).
"The data presented today demonstrate again that eculizumab has a profound impact on TMA — the underlying cause of life-threatening events in patients with aHUS — which leads to permanent discontinuation of plasma exchange, significant improvements in kidney function and other critical measures in these patients," said Chantal Loirat, M.D., Pediatric Nephrology Department, Hôpital Robert Debre, Paris.
Pediatric Patients
In a poster session on June 10, 2011, researchers presented data for the first time from a retrospective clinical study of 15 pediatric patients with aHUS who received at least one dose of eculizumab outside of prospective clinical trials between 2007 and 2009. All patients were under the age of 12 (under 2 years)
The analysis showed that eculizumab treatment significantly reduced TMA in pediatric patients with aHUS, as platelet counts were normalized in 93% (14/15) and 73% (11/15) of patients achieved TMA-event free status. Importantly, 53% of patients had improved renal function with eculizumab treatment. In addition, four of six patients with dialysis in the 30 days prior to eculizumab did not require dialysis during eculizumab treatment. Eculizumab efficacy was similar across all pediatric age groups. The most frequently reported adverse events were fever, upper respiratory tract infection, diarrhea and cough. The results in this pediatric population are consistent with those from controlled trials in adult and adolescent patients in demonstrating that eculizumab controlled TMA, improved kidney function and reduced the need for plasma exchange/infusion.
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