Data from Phase 2 Soliris Extension Studies Presented at ASN Meeting
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.1 The morbidity and premature mortality in aHUS is caused by chronic uncontrolled activation of the complement system, resulting in TMA, the formation of multiple blood clots in small blood vessels throughout the body.2,3 Soliris, a first-in-class terminal complement inhibitor, specifically targets uncontrolled complement activation, inhibiting complement-mediated TMA and its severe clinical consequences.
On
"Data presented today support that early and ongoing treatment with the complement inhibitor Soliris is beneficial for patients with aHUS," said
Patients with a Longer Duration of Disease Prior to Soliris Therapy (Previously Receiving Chronic PE/PI)
In a poster session today, researchers presented longer-term findings from a prospective, open-label, single-arm phase 2 trial of Soliris in adult and adolescent patients with a long duration of aHUS and prior treatment before starting on Soliris. Patients had been diagnosed with aHUS a median of 48 months prior to starting the study, and nearly all (90%) had chronic renal insufficiency at baseline (eGFR < 60 mL/min/1.73 m2). In the study, 20 patients received Soliris through week 26, and 19 patients continued into a long-term extension study and were evaluated at 62 weeks median duration of Soliris treatment (range of 26-74 weeks).
The primary endpoint of TMA event-free status (at least 12 consecutive weeks of stable platelet count, no PE/PI, and no new dialysis) was achieved by 16 of 20 Soliris-treated patients (80%) by week 26 and was sustained through the extension study, indicating that chronic treatment with Soliris continued to significantly inhibit complement-mediated TMA and progression of kidney dysfunction. Hematologic normalization was achieved in 18 of 20 Soliris-treated patients (90%) and was sustained through data cut-off. Importantly, PE/PI was eliminated in 100% of patients and no patients required new dialysis through week 26 and through data cut-off.
Ongoing Soliris treatment was associated with a highly significant and continuous, time-dependent improvement in eGFR (6 mL/min/1.73m2 [95%CI: 3, 9]) through week 26 and throughout the extension study (p<0.0001). Nine out of 20 patients (45%) also improved ≥1 chronic kidney disease (CKD) stage from baseline through data cut-off. Notably, earlier intervention with Soliris was associated with an increased likelihood of improved kidney function, as measured by eGFR, at week 26 (p=0.04). In addition, 73% of patients achieved a clinically meaningful benefit in health-related quality of life through week 26, and maintained this benefit with longer-term treatment.
"This study in patients with a long duration of disease and substantial renal damage prior to starting on Soliris, showed that continued treatment with Soliris led to sustained suppression of TMA, stabilized or even improved kidney function, and permanent discontinuation of plasma exchange or infusion," said
Soliris was well tolerated in the study. The most common drug-related adverse events (AEs) were headache, leukopenia and lymphopenia.
Patients with Shorter Duration of Disease Prior to Soliris Therapy and Progressive TMA Complications Despite Intensive PE/PI
In another poster session today, researchers presented longer-term data from a prospective, open-label, single-arm phase 2 study in adult and adolescent patients with progressive clinical TMA complications despite intensive PE/PI. Patients had been diagnosed with aHUS a median of 10 months before the start of the study, and 71% had severe renal impairment (eGFR <30 mL/min/1.73m2) at baseline. Seventeen patients were enrolled in the study and 15 were treated with Soliris for 26 weeks. Thirteen patients continued into the long-term extension study and were evaluated at 64 weeks median duration of Soliris treatment (range of 2-90 weeks).
In the primary endpoint, mean platelet count increased 73x109/L (P=0.0001) from baseline through week 26 and was sustained through the extension study, indicating ongoing inhibition of complement-mediated TMA. All patients (100%) with low platelets at baseline who continued on chronic Soliris treatment through week 26 achieved platelet normalization, and all 13 patients who entered the extension study and continued on treatment maintained normal platelet levels. TMA event-free status was achieved in 15 of 17 Soliris-treated patients (88%) through week 26, and all 13 patients (100%) who entered the extension study sustained their TMA event-free status through each data cut-off point. Hematologic normalization was achieved in 13 of 17 Soliris-treated patients (76%), which was sustained through all data cut-off points. These results demonstrated that chronic treatment with Soliris inhibits complement-mediated TMA.
Researchers also observed that ongoing Soliris treatment was associated with a highly significant and continuous, time-dependent improvement in eGFR with a mean change from baseline of 31 mL/min/1.73m2 through 26 weeks (p=0.0001) and one year (p=0.0005); in addition, four out of five (80%) patients eliminated dialysis with chronic Soliris treatment. Importantly, earlier initiation of Soliris treatment was associated with an increased likelihood of improved eGFR through week 26 (p=0.03). In addition, 80% of patients achieved a clinically meaningful change in health-related quality of life through week 26, increasing to 87% through the extension study.
"Sustained treatment with Soliris, particularly when initiated earlier, provided significant and persistent benefits for patients with aHUS in this study," said
Soliris was well tolerated in this study. The most common drug-related AEs were leukopenia, nausea, and vomiting.
About aHUS
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.5 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.7 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
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
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
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 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. Dr.
5. 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.
203-271-8210
or
212-508-9642
or
917-322-2569
Source:
News Provided by Acquire Media