“Extensive clinical data and real-world clinical experience spanning more than 10 years further establish the benefits that Soliris is providing to patients with PNH,” said Leonard Bell, M.D., Chief Executive Officer of Alexion. “The presentation of the two-year aHUS data also demonstrates the continued benefits of long-term Soliris therapy in patients with aHUS, and underscores the important role of hematologists in diagnosing and treating patients with this severe and ultra-rare complement-mediated disease.”Ten-Year Experience with Soliris in All Patients with PNH Treated in the UK In a poster presentation today, researchers presented data from all 153 patients who participated in a nationally commissioned PNH service led by two UK medical centers. The objective of the study was to describe the long-term safety, efficacy, and outcomes in patients with PNH from the UK who received Soliris treatment from May 2002 to April 2012. 1 The results demonstrated that the significant clinical benefits and long-term safety of Soliris were sustained over 10 years of chronic treatment. The investigators reported that long-term Soliris treatment led to an improvement in survival when compared with historical controls, and a significant reduction in the incidence of TE. 8,9 Researchers also reported data on the effect of discontinuation of anti-coagulant therapy in selected PNH patients. Transfusion independence was observed in the majority of patients, and the number of units transfused was significantly reduced in those patients still receiving transfusions. Results also confirmed the long-term safety and efficacy of continuous Soliris treatment. 1 Researchers presented the following data in support of these conclusions: 1
- Long-term Soliris therapy significantly reduced intravascular hemolysis by 83.4%, as assessed by levels of LDH (p<0.001).
- The researchers noted that UK patients on long-term Soliris therapy had improved survival compared with previously published historical controls. 8,9 Researchers also compared the survival of PNH patients treated with Soliris to a normal population of the same age and gender. Although the survival of PNH patients after 10 years of Soliris therapy was slightly inferior to this normal healthy population group, the causes of death in PNH patients were related to bone marrow failure and not due to hemolysis or TE associated with the underlying PNH.
- In the 12 months prior to starting Soliris, 36 thrombotic episodes were reported in 22 patients. None of those patients had a further thrombotic episode while on Soliris therapy. In the most recent 12 months on therapy, TEs were significantly reduced with only 3 events reported in a total of 3 patients (p<0.05).
- Of 117 patients transfused in the 12 months before receiving Soliris, 77 (65.8%) were transfusion-independent in the most recent 12 months on treatment. Among those patients still receiving transfusions (n=40), there was a significant 69% reduction in the number of units transfused, from a median of 26 units, 12 months before therapy, to 8 units in the most recent 12 months on therapy (P<0.05).
- In a poster presentation on December 8, researchers in South Korea evaluated the risk of TE in patients with PNH and elevated hemolysis (as identified by LDH ≥1.5 x ULN) in addition to any of the four clinical symptoms of abdominal pain, chest pain, dyspnea, or hemoglobinuria, compared with patients who had elevated LDH alone. The analyses confirm that elevated hemolysis was associated with a seven-fold increased risk of TE in patients with PNH. The risk of TE was significantly further increased in patients with elevated hemolysis and additional symptoms of abdominal pain, chest pain, dyspnea or hemoglobinuria compared with patients without the symptom and LDH <1.5 x ULN. These results underscore the importance of early therapeutic intervention and monitoring of PNH patients with elevated LDH. 4
- In a separate poster presentation on December 8, data supported the need to test high-risk PNH patients for diagnostic markers as an aid to treatment selection. Researchers presented an updated analysis of 7,699 high-risk patients whose blood cells were screened for a PNH clone using high-sensitivity flow cytometry. Among the 481 PNH-positive patients, those with large PNH clone sizes (>20%) were found to be more likely to have clinical symptoms, particularly those associated with hemolysis, and were thus deemed more likely to benefit from therapy. 13
- A poster presentation today identified a polymorphism in the terminal complement protein C5 that appears to be associated with no or minimal reduction in LDH in nine Japanese patients with PNH who received Soliris therapy, although there is no evidence of the mutation outside of Japan or in any other Asian populations. The study authors concluded that further research is needed to verify that the polymorphism in the C5 gene is responsible for the suboptimal reduction in LDH and to determine a more accurate prevalence of this C5 polymorphism in Japanese populations. 5