Alexion Pharmaceuticals has announced that researchers presented data from  four clinical trials, all demonstrating the clinical benefits of Soliris (eculizumab) for the treatment of atypical hemolytic uremic syndrome (aHUS), a genetic, chronic, ultra-rare disease associated with vital  organ failure and premature death. Soliris is the first and only approved safe and effective treatment for pediatric and adult patients with aHUS. In two large, prospective, multinational studies, Soliri inhibited systemic complement-mediated thrombotic microangiopathy (TMA, the formation of blood clots in small blood vessels throughout the body) and improved renal function in both pediatric and adult patients with aHUS. The data were presented at Kidney Week 2013, the annual meeting of the American Society of Nephrology (ASN).

The ASN meeting also featured the presentation of three-year update data from two pivotal phase II extension studies that highlighted the long-term benefits of Soliris therapy in patients with aHUS. In these  studies, ongoing Soliris treatment at the three-year update was  associated with sustained inhibition of complement-mediated TMA, as indicated by stabilization or continued improvement in key hematologic  and renal endpoints, and quality of life. Additionally, investigators presented initial characteristics from patients enrolled in a global aHUS Registry, which is prospectively collecting information to enhance understanding of the disease process in order to help optimize care and improve quality-of-life for patients with aHUS.

aHUS is an ultra-rare, life-threatening, chronic genetic disease that can progressively damage vital organs, leading to stroke, heart attack,  kidney failure and death. The morbidities and premature mortality in aHUS are caused by chronic, uncontrolled activation of the complement system, resulting in systemic TMA. Soliris, a first-in-class terminal complement inhibitor, specifically targets uncontrolled complement activation, and is the first and only approved treatment for patients with aHUS in the U.S., E.U., Japan and other countries.

"Results from four prospective studies demonstrate a significant and sustained inhibition of complement-mediated TMA with Soliris treatment and support the chronic use of Soliris in pediatric and adult patients with aHUS," said Leonard Bell, CEO of Alexion. "These studies further underscore the rationale for initiating Soliris therapy at the time of clinical diagnosis of aHUS and chronic treatment of patients to achieve optimal outcomes."

Researchers have presented positive results from the first prospective trial of Soliris in pediatric patients with aHUS, which follows the previously presented positive results of a retrospective study in pediatric patients with aHUS. This open-label, prospective, single-arm, multinational trial enrolled  a heterogeneous population of patients who were >1 month old and

Two patients (9%) had received a prior kidney transplant. The primary endpoint of the study was the proportion of patients with a complete TMA response, defined as platelet count normalization, lactate  dehydrogenase (LDH) normalization, and >25% improvement in serum creatinine from baseline, during 26 weeks of treatment.

In the study, the median time from current manifestation of aHUS to first dose of Soliris was six days. Nineteen patients (86%) completed the initial 26 weeks of Soliris therapy, and 14 of 22 patients (64%)  achieved the study's primary endpoint of complete TMA response at 26  weeks, which required significant improvement in renal function (>25% decrease in creatinine). Platelet count normalization was achieved  in 21 of the 22 patients (95%); the median time to platelet count  normalization was seven days and the mean improvement in platelet count  from baseline was 164 x10(9)/L (p

In terms of renal parameters, the mean estimated glomerular filtration rate(eGFR) increase from baseline was 64mL/min/1.73m(2) (P

In an oral presentation on Nov. 8, researchers presented positive new data from the largest prospective trial of Soliris in adult patients with aHUS. This open-label, single-arm, multinational trial enrolled 41 adult patients with aHUS representing a broad patient population.  Prior PE/PI was not required for inclusion in the study, and the median time from aHUS manifestation to first dose of Soliris was approximately two weeks. Thirty of 41 patients (73%) in the study were newly diagnosed, six patients (15%) had no PE/PI during the current clinical manifestation, 24 patients (59%) were on dialysis at baseline, nine patients (22%) had a prior kidney transplant and 20 patients (49%) had an identified complement factor mutation. All endpoints were evaluated at 26 weeks of treatment in an intent-to-treat analysis, and 38 (93%) of enrolled patients completed the 26-week study period. The primary endpoint of the study was the proportion of patients with complete TMA response, as measured by platelet count normalization, LDH normalization and preservation of renal function (

The study met its primary endpoint, with 30 of 41 patients (73%) achieving a complete TMA response at 26 weeks.  Forty of 41 patients (98%) achieved platelet count normalization (>=150 x10(9)/L) by week 26, and the mean increase in platelet count from baseline was 135x10(9)/L (P

Soliris significantly improved renal function with a mean increase in eGFR from baseline of 29 mL/min/1.73m (P

Researchers also presented findings from a three-year update of a prospective, open-label, single-arm phase 2  trial of Soliris in 20 adult and adolescent patients with a long  duration of aHUS and chronic kidney disease (CKD) who were undergoing  prolonged PE/PI before starting treatment with Soliris. Patients had been diagnosed with aHUS a median of 48 months prior to starting the study. Twenty patients were enrolled in the initial study and received Soliris for 26 weeks. Nineteen of the 20 patients continued into a long-term extension phase; 16 patients were treated for 30 months or more and 10 patients remained enrolled in the trial at three years. Patients were evaluated for a median duration of 156 weeks. The co-primary endpoints were TMA event-free status and hematologic normalization.

According to investigators, in aHUS patients with long disease duration and CKD, long-term treatment with Soliris led to improvements in hematologic and renal function over 3 years. Treatment with Soliris resulted in achievement of TMA event-free status (at least 12 consecutive weeks of stable platelet count, no PE/PI, and no new dialysis) and hematologic normalization in most patients by three years.

By the three-year update, 19 of 20 patients (95%) had achieved TMA event-free status and 18 of 20 (90%) had achieved hematologic normalization. Significant improvements in eGFR were observed by week four (P

Researchers presented results from a three-year update of a prospective, open-label, single-arm phase II study in17 adult and adolescent patients with aHUS who had presented with active, progressing TMA. Seventeen patients were enrolled in the initial study and received Soliris for 26 weeks. Thirteen of the 17 patients continued into a long-term extension phase.

In patients with aHUS and clinical evidence of progressing TMA, investigators reported that long-term Soliris treatment inhibited complement-mediated TMA, as measured by rapid and sustained improvement in platelet count over three years (mean change from baseline, P=0.0001 at 26 weeks and P

Also on Nov. 9, Christoph Licht, M.D., FASN, associate professor of paediatrics, division of nephrology at The Hospital for Sick Children, University of Toronto, presented baseline demographics from the initial patients enrolled in the global aHUS Registry, which was established in April 2012 to prospectively collect information on patients with aHUS. As of September, a total of 211 patients had enrolled in the global aHUS patient registry. The results and analyses collected within the Registry will increase awareness and understanding of aHUS disease history and progression in order to help optimize care and improve quality of life for patients with aHUS.