Soliris® and PNH
Soliris® (eculizumab) is the first and only therapy approved for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis.1 Soliris is approved for the treatment of patients with PNH in nearly 50 countries worldwide, including the United States (U.S.), European Union (EU), and Japan.
PNH is an ultra-rare, life-threatening blood disorder in which uncontrolled activation of complement, a component of the normal immune system, results in chronic hemolysis (destruction of the patient’s red blood cells).2,3 Chronic hemolysis is the main cause of serious health problems in people with PNH and can lead to blood clots, organ failure and premature death.3-5 In healthy individuals, normal red blood cells (RBCs) are protected from complement attack by a shield of terminal complement inhibitors. These protective proteins inhibit uncontrolled complement activation and chronic hemolysis. In patients with PNH, the lack of these protective proteins renders RBCs vulnerable to lysis by complement. Without this protective complement inhibitor shield, PNH RBCs are destroyed (hemolysis), which can result in thrombosis, end organ damage, and increased mortality.6
PNH develops without warning and can occur in men and women of all races, backgrounds and ages.7 While the average age of onset is in the early 30s, approximately 10% of patients first develop symptoms at age 21 or younger.8 Prior to the approval of Soliris, up to 35% of patients with PNH treated with available supportive care did not survive beyond five years from diagnosis due to serious clinical outcomes such as thromboembolism (blockage of a blood vessel by a blood clot) and chronic kidney disease (CKD).3,5
Treating Patients Who Have PNH with Soliris
Today, patients with PNH have the benefit of an approved therapy for the treatment of their condition. Soliris works by inhibiting terminal complement, which reduces hemolysis, improves symptoms and reduces many of the major health complications associated with PNH.9,10
IMPORTANT SAFETY INFORMATION FOR SOLIRIS
WARNING: SERIOUS MENINGOCOCCAL INFECTIONS
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 [see Warnings and Precautions (5.1)].
Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccination in patients with complement deficiencies.
Immunize patients with a meningococcal vaccine at least 2 weeks prior to administering the first dose of Soliris, unless the risks of delaying Soliris therapy outweigh the risk 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 [see Warnings and Precautions (5.2)]. Enrollment in the Soliris REMS program and additional information are available by telephone: 1-888-SOLIRIS (1-888-765-4747) or at solirisrems.com.
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 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]. New Haven, CT: Alexion Pharmaceuticals Inc; 2016.
Hill A, Richards SJ, Hillmen P. Recent developments in the understanding and management of paroxysmal nocturnal haemoglobinuria. Br J Haematol. 2007 May;137(3):181-92.
Hillmen P, Lewis SM, Bessler M, Luzzatto L, Dacie JV. Natural history of paroxysmal nocturnal hemoglobinuria. N Engl J Med. 1995 Nov 9;333(19):1253-8.
Rother RP, Bell L, Hillmen P, Gladwin MT. The clinical sequelae of intravascular hemolysis and extracellular plasma hemoglobin: a novel mechanism of human disease. JAMA. 2005 Apr 6;293(13):1653-62.
Nishimura J, Kanakura Y, Ware RE, et al. Clinical course and flow cytometric analysis of paroxysmal nocturnal hemoglobinuria in the United States and Japan. Medicine (Baltimore). 2004 May;83(3):193-207.
Rosse W. Paroxysmal Nocturnal Hemoglobinuria. Hoffman: Hematology: Basic Principles and Practice. 3 ed. Churchill Livingstone, Inc.; 2000.
Socie G, Mary JY, de Gramont A., et al. Paroxysmal nocturnal haemoglobinuria: long-term follow-up and prognostic factors. French Society of Haematology. Lancet. 1996 Aug 31;348(9027):573-7.
Parker C, Omine M, Richards S, Nishimura J, Bessler M, Ware R, et al. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood. 2005 Dec 1;106(12):3699-709.
Rother RP, Rollins SA, Mojcik CF, Brodsky RA, Bell L. Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria. Nat Biotechnol. 2007 Nov;25(11):1256-64.
Hillmen P, Muus P, Duhrsen U, et al. Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria. Blood. 2007 Dec 1;110(12):4123-8.