Soliris® and aHUS
Soliris® (eculizumab) is the first and only therapy approved for the treatment of atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated microangiopathy.1 Soliris is approved for the treatment of patients with aHUS in more than 40 countries, including the United States (U.S.), European Union (EU), and Japan.
aHUS is a genetic, chronic, ultra-rare disease that can progressively damage vital organs, potentially leading to stroke, heart attack, kidney failure, and premature death. aHUS is caused by genetic abnormalities that result in chronic uncontrolled complement activation leading to complement-mediated thrombotic microangiopathy (TMA) — the formation of blood clots in small blood vessels throughout the body.2,3
aHUS affects both adults and children. Patients with aHUS face a lifelong risk of TMA, which may lead to sudden, catastrophic, and life-threatening damage to the kidney, brain, heart, and other vital organs, and premature death.2,3
Prior to the approval of Soliris for the treatment of aHUS, doctors relied on disease management strategies that did not specifically target uncontrolled complement activation, the underlying cause of TMA. Seventy-nine percent (79%) of all patients with aHUS died, required kidney dialysis, or had permanent kidney damage within three years after diagnosis despite plasma exchange or plasma infusion.5 Moreover, 33 to 40 percent of patients died or progressed to end-stage renal disease with the first clinical manifestation of aHUS despite supportive care.5,6
Treating Patients with aHUS with Soliris
As a first-in-class treatment that specifically targets uncontrolled complement activation in patients with aHUS, Soliris represents a major step forward in the care of adults and children with this disease. In clinical studies, patients with aHUS experienced a reduction in terminal complement activity after the first dose, and this reduction was sustained with ongoing Soliris treatment.7,8,9
IMPORTANT SAFETY INFORMATION FOR SOLIRIS
WARNING: SERIOUS MENINGOCOCCAL INFECTIONS
See full prescribing information for the complete boxed warning.
Life-threatening and fatal meningococcal infections have occurred in patients treated with Soliris and may become rapidly life-threatening or fatal if not recognized and treated early.
Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccination in patients with complement deficiencies.
Immunize patients with meningococcal vaccines at least 2 weeks prior to administering the first dose of Soliris unless the risks of delaying Soliris therapy outweigh the risks of developing a meningococcal infection. [See Warnings and Precautions (5.1) for additional guidance on the management of the risk of meningococcal infection.]
Monitor patients for early signs of meningococcal infections, and evaluate immediately if infection is suspected.
Soliris is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS). Under the Soliris REMS, prescribers must enroll in the program.
Indications and Usage
Paroxysmal Nocturnal Hemoglobinuria (PNH)
Soliris is indicated for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis.
Atypical Hemolytic Uremic Syndrome (aHUS)
Soliris is indicated for the treatment of patients with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy.
Limitation of Use
Soliris is not indicated for the treatment of patients with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS).
Soliris is contraindicated in:
Patients with unresolved serious Neisseria meningitidis infection
Patients who are not currently vaccinated against Neisseria meningitidis, unless the risks of delaying Soliris treatment outweigh the risks of developing a meningococcal infection
Warnings and Precautions
Soliris blocks terminal complement activation; therefore patients may have increased susceptibility to infections, especially with encapsulated bacteria. Additionally, Aspergillus infections have occurred in immunocompromised and neutropenic patients. Children treated with Soliris may be at increased risk of developing serious infections due to Streptococcus pneumoniae and Haemophilus influenza type b (Hib). Administer vaccinations for the prevention of Streptococcus pneumoniae and Haemophilus influenza type b (Hib) infections according to ACIP guidelines. Use caution when administering Soliris to patients with any systemic infection.
Monitoring Disease Manifestations After Soliris Discontinuation
Treatment Discontinuation for PNH
Monitor patients after discontinuing Soliris for at least 8 weeks to detect hemolysis.
Treatment Discontinuation for aHUS
After discontinuing Soliris, monitor patients with aHUS for signs and symptoms of thrombotic microangiopathy (TMA) complications for at least 12 weeks. In aHUS clinical trials, 18 patients (5 in the prospective studies) discontinued Soliris treatment. TMA complications occurred following a missed dose in 5 patients, and Soliris was reinitiated in 4 of these 5 patients.
Clinical signs and symptoms of TMA include changes in mental status, seizures, angina, dyspnea, or thrombosis. In addition, the following changes in laboratory parameters may identify a TMA complication: occurrence of two, or repeated measurement of any one of the following: a decrease in platelet count by 25% or more compared to baseline or the peak platelet count during Soliris treatment; an increase in serum creatinine by 25% or more compared to baseline or nadir during Soliris treatment; or, an increase in serum LDH by 25% or more over baseline or nadir during Soliris treatment.
If TMA complications occur after Soliris discontinuation, consider reinstitution of Soliris treatment, plasma therapy [plasmapheresis, plasma exchange, or fresh frozen plasma infusion (PE/PI)], or appropriate organ-specific supportive measures.
Thrombosis Prevention and Management
The effect of withdrawal of anticoagulant therapy during Soliris treatment has not been established. Therefore, treatment with Soliris should not alter anticoagulant management.
As with all protein products, administration of Soliris may result in infusion reactions, including anaphylaxis or other hypersensitivity reactions. In clinical trials, no patients experienced an infusion reaction which required discontinuation of Soliris. Interrupt Soliris infusion and institute appropriate supportive measures if signs of cardiovascular instability or respiratory compromise occur.
The most frequently reported adverse reactions in the PNH randomized trial (≥10% overall and greater than placebo) are: headache, nasopharyngitis, back pain, and nausea.
The most frequently reported adverse reactions in aHUS single-arm prospective trials (≥20%) are: headache, diarrhea, hypertension, upper respiratory tract infection, abdominal pain, vomiting, nasopharyngitis, anemia, cough, peripheral edema, nausea, urinary tract infections, pyrexia.
Please see full prescribing information for Soliris, including boxed WARNING regarding serious meningococcal infection.
Soliris [package insert]. Alexion Pharmaceuticals Inc; revised 1/2016.
Benz K, Amann K. Thrombotic microangiopathy: new insights. Curr Opin Nephrol Hypertens. 2010;19(3):242-7.
Tsai HM. The molecular biology of thrombotic microangiopathy. Kidney Int. 2006;70(1):16-23.
Ariceta G, Besbas N, Johnson S, et al. Guideline for the investigation and initial therapy of diarrhea-negative hemolytic uremic syndrome. Pediatr Nephrol. 2009;24:687-96.
Noris M, Remuzzi G. Atypical hemolytic-uremic syndrome. N Engl J Med. 2009;361:1676-87.
Caprioli J, Noris M, Brioschi S, et al. The impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome. Blood. 2006;108:1267-1269.
Abstract 1587 entitled “A phase II study of eculizumab in patients with atypical hemolytic uremic syndrome receiving chronic plasma exchange/infusion,” presented by Dr. Chantal Loirat at the 16th Congress of the European Hematology Association, Sunday, June 12, 2011.
Abstract 1588 entitled “Eculizumab efficacy and safety in patients with atypical hemolytic uremic syndrome resistant to plasma exchange/infusion,” presented by Dr. Chantal Loirat at the 16th Congress of the European Hematology Association, Sunday, June 12, 2011.
Abstract 396 entitled “Eculizumab therapy for atypical hemolytic uremic syndrome in pediatric patients: Efficacy and safety outcomes from a retrospective study,” presented by Dr. Giacomo Simonetti at the 16th Congress of the European Hematology Association, Friday, June 10, 2011.