— First and Only Approved Treatment in both
The morbidity and premature mortality in aHUS are caused by chronic uncontrolled activation of the complement system, resulting in the formation of multiple blood clots in small blood vessels throughout the body, known as thrombotic microangiopathy or TMA.2,3 Despite historical supportive care, more than half of all patients with aHUS die, require kidney dialysis or have permanent kidney damage within 1 year of diagnosis.4
"The approval of Soliris for aHUS in
Soliris, a first-in-class terminal complement inhibitor, specifically targets uncontrolled complement activation. The EC has granted marketing authorization for Soliris to treat pediatric and adult patients with aHUS. The Clinical Particulars section of the EU label states, "Soliris treatment is recommended to continue for the patient's lifetime, unless the discontinuation of Soliris is clinically indicated," as described in the Special warnings and precautions for use subsection. Alexion will begin reimbursement discussions with healthcare authorities in major European countries, and expects to start serving patients with aHUS in initial major European countries in the first half of 2012, with additional major European countries commencing through mid-2013.
"The EC approval marks another milestone for Soliris and brings life-transforming hope another step closer to families in
Soliris was previously approved by the
Soliris in aHUS Clinical Data
The approval of Soliris for the treatment of aHUS is based on clinical data from two prospective, controlled, open-label studies in adolescent and adult patients with aHUS, and a third retrospective study in pediatric patients with aHUS, which together included a broad range of aHUS patients. All patients treated with Soliris when administered as recommended demonstrated rapid and sustained reduction in terminal complement activity, and chronic administration of Soliris resulted in rapid and sustained reduction in complement-mediated TMA.
In study C08-003 A/B, which included 20 patients with a long duration of aHUS and prior treatment before starting on Soliris,16 out of 20 Soliris-treated patients (80%) achieved TMA event-free status, defined as at least 12 consecutive weeks of stable platelet count, no plasma exchange/plasma infusion (PE/PI), and no new dialysis. Hematologic normalization was achieved in 18 of 20 Soliris-treated patients (90%). Renal function, as measured by eGFR, increased during Soliris therapy, and no patient required new dialysis.
In study C08-002 A/B, which included 17 patients with progressive clinical TMA complications despite intensive PE/PI, Soliris inhibited complement-mediated TMA as shown by a significant improvement in platelet count from baseline through week 26 of 73×109/L (p=0.0001). Hematologic normalization was observed in 13 of 17 Soliris-treated patients (76%), and TMA event-free status (stable platelet count, no PE/PI, and no new dialysis) was achieved by 15 of 17 Soliris-treated patients (88%). Renal function, as measured by eGFR, was significantly improved during Soliris therapy, and four out of five patients who required dialysis at study entry were able to discontinue dialysis for the duration of treatment. Patients also reported improved health-related quality of life.
Study C009-001r included 15 pediatric patients (ages 2 months to <12 years) who received Soliris outside of prospective clinical trials and with or without prior PE/PI. Platelet count was normalized in 14 of 15 Soliris-treated patients (93%). All patients treated with Soliris also achieved a reduction in the TMA intervention rate. The efficacy results for these pediatric patients appeared consistent with results for patients enrolled in the prospective aHUS studies. No pediatric patient required new dialysis during treatment with Soliris.
Soliris was well tolerated in these clinical studies. The most frequently reported adverse events were hypertension, upper respiratory tract infection, and diarrhea.
aHUS is a chronic, ultra-rare, and life-threatening disease in which a genetic deficiency in one or more complement regulatory genes causes life-long uncontrolled complement activation, resulting in complement-mediated thrombotic microangiopathy (TMA), the formation of blood clots in small blood vessels throughout the body.1,2 Permanent, uncontrolled complement activation in aHUS causes a life-long risk for TMA, which leads to sudden, catastrophic, and life-threatening damage to the kidney, brain, heart, and other vital organs, and premature death. 2,3 More than half of all patients with aHUS die, require kidney dialysis or have permanent kidney damage within 1 year of diagnosis.4 The majority of patients with aHUS who receive a kidney transplant commonly experience subsequent systemic TMA, resulting in a 90% transplant failure rate.6
aHUS affects both children and adults. In a large group of aHUS patients, 60% were first diagnosed at younger than 18 years of age.6 Complement-mediated TMA also causes reduction in platelet count (thrombocytopenia) and red blood cell destruction (hemolysis). While mutations have been identified in at least ten different complement regulatory genes, mutations are not identified in 30-50% of patients with a confirmed diagnosis of aHUS.7
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
Soliris is generally well tolerated in patients with PNH and aHUS. 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.
The U.S. product label for Soliris also 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
Prior to beginning Soliris therapy, all patients and their prescribing physicians in
Please see full prescribing information for Soliris, including boxed WARNING regarding risk of serious meningococcal infection.
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 aHUS. 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
References and Footnotes
1. Noris M, Remuzzi G: Atypical hemolytic-uremic syndrome. N Engl J Med 2009 361:1676-87
2. Benz K,
3. Tsai HM. The molecular biology of thrombotic microangiopathy. Kidney Int 2006 Jul;70(1):16-23.
4. Caprioli J, Noris M, Brioschi S, et al; for the International Registry of Recurrent and Familial HUS/TTP. Genetics of HUS: the impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome. Blood. 2006;108:1267-1279.
6. Bresin E, Daina E, Noris M, et al; International Registry of Recurrent and Familial HUS/TTP. Outcome of renal transplantation in patients with non—Shiga toxin-associated hemolytic uremic syndrome: prognostic significance of genetic background. Clin J Am Soc Nephrol. 2006;1:88-99.
7. Noris M, Caprioli J, Bresin E, et al. Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype. Clin J Am Soc Nephrol. 2010;5:1844-1859.
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