Alexion Pharmaceuticals presented data from 4 clinical trials that examined the efficacy and safety of its orphan drug Soliris® (eculizumab) for the treatment of atypical hemolytic uremic syndrome (aHUS) - a genetic, ultra-rare disease associated with vital organ failure and premature death. At the annual meeting of the American Society of Nephrology (ASN) this past week (ie, Kidney Week 2013), data was presented that showed Soliris to inhibit 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. Data was also presented on showing the drug is effective long term (i.e., 3 years) in different patient populations.
Regarding the plethora of results presented, Leonard Bell, Chief Executive Officer of Alexion stated, “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,” adding, “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.”
Below are a summary of the 4 abstracts.
Soliris in Pediatric Patients with aHUS (Abstract SA-PO0849)
Greenbaum et al  presented data from an open-label, prospective, single-arm, multinational trial that looked at the efficacy and safety of Soliris in 22 pediatric patients (>1 month old and <18 years of age) with aHUS (16 newly diagnosed). 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.
Results: 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. In addition, platelet count normalization was achieved in 21 of the 22 patients and hematologic normalization was observed in 18 of 22 patients (82%). All patient (n=10) who had prior plasma exchange or infusion (PE/PI) at baseline no longer required PE/PI by the end of the 26-week study. The most common adverse events (AEs) were fever (50%) and cough (36%).
In a press release, Lead author Larry Greenbaum, M.D., Ph.D., Director of Pediatric Nephrology at Emory University and Children's Healthcare of Atlanta said, “This was the first prospective study of pediatric patients with aHUS, and demonstrated that chronic Soliris treatment led to rapid and sustained improvement in platelet counts and significant improvement in kidney function, including discontinuation of dialysis.”
Soliris in Adult Patients with aHUS (Abstract FR-OR057)
Fakhouri et al  presented data from an open-label, single-arm, multinational trial that looked at the efficacy and safety of Soliris in 41 adult patients with aHUS (30 newly diagnosed, 6 patients had no PE/PI during the current clinical manifestation, 24 patients were on dialysis at baseline, 9 patients had a prior kidney transplant, and 20 patients had an identified complement factor mutation). The primary endpoint was the proportion of patients with complete TMA response, as measured by platelet count normalization, LDH normalization and preservation of renal function (<25% increase in serum creatinine from baseline), at 26 weeks.
Results: The study met its primary endpoint, with 73% achieving a complete TMA response at 26 weeks. Forty of 41 patients (98%) achieved platelet count normalization (≥150 x109/L) by week 26, and the mean increase in platelet count from baseline was 135x109/L (P<0.0001), demonstrating inhibition of TMA. The most common AEs were headache (37%), diarrhea (32%) and peripheral edema (22%).
Long Term (3 year) Treatment with Soliris in Patients with Long Duration of aHUS and CKD (Abstract SA-PO850)
Delmas et al  presented results from a three-year extension of a 26 week, open label single arm phase 2 study that had involved 20 adult and adolescent patients with long duration of aHUS and chronic kidney disease (CKD) treated with Soliris. Nineteen of the 20 patients continued the extension phase with 16 patients treated for 30 months or more and 10 patients still enrolled at the 3 year mark. Patients were evaluated for a median duration of 156 weeks. The co-primary endpoints were TMA event-free status and hematologic normalization.
Results: Long-term treatment with Soliris in aHUS patients with long disease duration and CKD led to improvements in hematologic and renal function over 3 years. By the 3-year update, 19 of 20 patients (95%) had achieved TMA event-free status and 18 of 20 (90%) had achieved hematologic normalization. Soliris therapy was safe and there were no meningococcal infections in patients over 3 years of treatment.
In a press release, lead author Yahsou Delmas, M.D., Ph.D., at Nephrology Unit, Clearing University Hospital, Bordeaux in Bordeaux, France said, “These data indicate that significant and time-dependent improvement in kidney function can be obtained with long-term eculizumab therapy, even in aHUS patients with a history of chronic kidney damage."
Long Term (3 year) Treatment with Soliris in Patients with Progressing TMA Despite Intensive PE/PI (Abstract SA-PO852)
Gaber et al  presented a three-year update of a 26 week Phase 2 study involving 14 of the original 17 adult and adolescent patients with aHUS who had presented with active, progressing TMA.
Results: 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<0.0001 at 3 years), as well as early achievement of hematologic normalization and TMA event-free status (at least 12 consecutive weeks of stable platelet count, no PE/PI, and no new dialysis).
In a press release, lead author A. Osama Gaber, Professor of Surgery at Weill Cornell Medical College and Director of the Methodist J.C. Walter Transplant Center at The Methodist Hospital in Houston, Texas said, “The three-year safety and efficacy update data from this study highlight the durability of Soliris and support the benefit of continued therapy in patients with aHUS,” adding, “The data also support that continued treatment with Soliris maintains beneficial long-term patient outcomes in patients at risk from life-threatening complications of TMA.”
Some of these results will also be presented at next month’s American Society of Hematology (ASH) Annual Meeting.
About aHUS and Soliris
aHUS is a chronic, ultra-rare, and life-threatening disease that can lead to progressive renal problems. A common problem in these patients is formation of complement-mediated TMA – or blood clots in small blood vessels throughout the body. According to Alexion, 65% of all patients with aHUS die, require kidney dialysis, or have permanent kidney damage within the first year after diagnosis despite plasma exchange or plasma infusion (PE/PI). The data presented on Soliris continues to show that it can greatly improve outcomes in many of these patients.
Soliris is a first-in-class terminal complement inhibitor developed from the laboratory through regulatory approval and commercialization by Alexion. Soliris is approved in the US treating patients with paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS).