— 28-Week Data from Full Cohort of 198 Patients Show Rapid and Sustained Improvement in Thrombotic Microangiopathy (TMA) and Reversal of Organ Damage —
— Improvements in Key Secondary Endpoints Also Reported at the ASN Annual Meeting —
The eculizumab 28-week data, presented today at Kidney Week 2012, the annual meeting of the
"In the study, patients had a robust response to eculizumab therapy. Patients achieved a substantial improvement in systemic TMA and vital organ involvement as early as 8 weeks, which was sustained through 28 weeks," said
STEC-HUS is a life-threatening disease characterized by systemic complement-mediated TMA and acute vital organ damage that can lead to serious, long-term complications. In STEC-HUS,
"STEC-HUS is an unpredictable, life-threatening disease with a high rate of long-term serious clinical sequelae and no approved treatment options that address the underlying pathogenesis of the disease," said
Eculizumab is approved in over 40 countries as a treatment for patients with paroxysmal nocturnal hemoglobinuria (PNH) and in the
About the Eculizumab Study
The 28-week, open-label, multi-center trial enrolled 198 STEC-HUS patients at 23 clinical trial sites with TMA (platelet decrease and evidence of hemolysis) and organ complications (evidence of kidney or central nervous system complications, or thrombosis). All patients showed severe, progressive disease at baseline: 96% had kidney involvement, 84% had brain involvement, 80% had involvement of both brain and kidney, 26% had seizures, 24% required respiratory support with mechanical ventilation, and 21% were in a coma. In addition, 91% of patients were receiving plasma exchange and 72% required dialysis at baseline prior to receiving eculizumab. Patients enrolled in the study received 900 milligrams (mg) of eculizumab each week for the first 3 weeks, followed by a 1200 mg dose on weeks 4, 6, and 8. After an initial 8-week eculizumab treatment period, study investigators were able to request treatment with eculizumab 1200 mg every other week for an additional 8 weeks. All patients in the study were observed for 28 weeks following eculizumab treatment initiation.1
Nearly all (94%) of the eculizumab-treated patients had a global response to therapy by 8 weeks, prospectively defined as either a complete response (CR), which consisted of hematologic normalization, clinically important improvement in all affected vital organs, and no clinically important worsening in any vital organ; or a partial response (PR), consisting of hematologic improvement or normalization and no clinically important worsening in any vital organ. Specifically, at 8 weeks, 80% of patients had a CR and 14% had a PR. By week 28, the overall response of 94% was sustained, and there was an increased rate of complete response from 80% to 89% between weeks 8 and 28.1
Results of the study also showed1:
- Rapid improvement in platelet count with eculizumab treatment, which was worsening prior to eculizumab.
- Rapid improvement in renal function with eculizumab treatment, as measured by normalization in serum creatinine, which was worsening prior to eculizumab.
- Elimination of dialysis and plasma exchange with eculizumab therapy: 84% of patients who required dialysis at baseline (115/137) discontinued dialysis by 3 weeks of eculizumab therapy. By week 8, 96% of patients had discontinued dialysis and by week 28, 99% of patients had discontinued dialysis. All of the patients who required plasma exchange at baseline (181/181) had discontinued plasma exchange by 4 weeks of eculizumab therapy.
- Improvement in neurological complications with eculizumab treatment: By week 8, 64% of patients had neurological normalization, defined as a shift from ≥2 at baseline on the Modified Rankin Scale (MRS), which measures neurologic morbidity, to a MRS score of 0-1 with eculizumab. By week 28, 91% of patients achieved MRS normalization.
- By week 28, 100% of patients were out of coma (35/35), 100% were free of seizures (43/43) and 100% had discontinued mechanical ventilation (47/47).
Eculizumab appeared to be well-tolerated in the study, with the three most common adverse events being headache, hypertension, and, alopecia. Most adverse events were reported as mild or moderate. There were no reported cases of meningococcal infection in the trial and no reported deaths. The study investigators determined that the adverse events in the trial were consistent with expected clinical STEC-HUS presentation.1
Post Hoc Matched-Control Analysis
An exploratory post hoc, matched-control analysis was performed based on data from patients with severe STEC-HUS who received eculizumab in this study (23 German sites) versus other patients who received current best supportive care only during the German epidemic (4 German sites). Patients were matched for specific baseline markers of disease severity, including organ involvement, neurologic involvement, dialysis and thrombocytopenia (a marker of ongoing TMA). The preliminary results showed that eculizumab treatment was associated with consistently higher rates of renal and neurological function improvement at weeks 8 and 28 compared to matched patients not treated with eculizumab.1
About STEC-HUS
STEC-HUS is an ultra-rare and life-threatening disease due to uncontrolled complement activation which causes platelet activation, thrombosis (blood clots), hemolysis (red blood cell destruction), and inflammation in small blood vessels throughout the body, a process known as systemic thrombotic microangiopathy, or systemic TMA.15 Due to systemic TMA, STEC-HUS patients are at risk of early, progressive and unpredictable damage to multiple vital organs including the brain, heart, lungs, kidneys and organs of the gastrointestinal system. This severe organ damage can cause significant and long-term morbidity in affected patients, and can also lead to mortality from STEC-HUS.16,17
Although similar in its life-threatening TMA clinical manifestations, STEC-HUS and the atypical form of hemolytic uremic syndrome (aHUS) are different diseases. aHUS is a life-long genetic disease with uncontrolled complement activation while in STEC-HUS the uncontrolled complement activation follows an isolated episode of infection by enterohemorrhagic Escherichia coli (EHEC).
About Soliris
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,
Important Safety Information
The US product label for Soliris includes a boxed warning: "Life-threatening and fatal meningococcal infections have occurred in patients treated with Soliris. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early. Comply with the most current
In patients with PNH, the most frequently reported adverse events observed with Soliris treatment in clinical studies were headache, nasopharyngitis (runny nose), back pain and nausea. Soliris treatment of patients with PNH should not alter anticoagulant management because the effect of withdrawal of anticoagulant therapy during Soliris treatment has not been established. In patients with aHUS, the most frequently reported adverse events observed with Soliris treatment in clinical studies were hypertension, upper respiratory tract infection, diarrhea, headache, anemia, vomiting, nausea, urinary tract infection, and leukopenia. Please see full prescribing information for Soliris, including boxed WARNING regarding risk of serious meningococcal infection.
About Alexion
[ALXN-G]
Safe Harbor Statement
This news release contains forward-looking statements, including statements related to anticipated clinical development, regulatory and commercial milestones and potential health and medical benefits of Soliris® (eculizumab) for the potential treatment of patients with STEC-HUS. Forward-looking statements are subject to factors that may cause Alexion's results and plans to differ from those expected, including for example, decisions of regulatory authorities regarding marketing approval or material limitations on the marketing of Soliris for its current or potential new indications, and a variety of other risks set forth from time to time in Alexion's filings with the
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