Soliris - Drug Monograph

Introduction

Soliris (eculizumab) is a first-in-class complement inhibitor developed by Alexion Pharmaceuticals. It is a recombinant humanized monoclonal antibody that specifically targets the complement protein C5, preventing its cleavage and subsequent formation of the membrane attack complex (MAC). Soliris represents a significant advancement in the treatment of several rare complement-mediated disorders and was the first medication approved for paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS).

Mechanism of Action

Soliris exerts its therapeutic effect by binding with high affinity to the complement protein C5, preventing its cleavage into C5a and C5b. This inhibition blocks the formation of the terminal complement complex C5b-9 (membrane attack complex or MAC). By inhibiting MAC formation, Soliris prevents complement-mediated intravascular hemolysis in PNH and thrombotic microangiopathy in aHUS. The drug specifically targets the alternative pathway of complement activation while preserving the early components of the complement cascade (C3 and below), which are essential for opsonization and immune complex clearance.

Indications

Soliris is FDA-approved for:

• Paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis
• Atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy
• Generalized myasthenia gravis (gMG) in anti-acetylcholine receptor (AChR) antibody-positive patients
• Neuromyelitis optica spectrum disorder (NMOSD) in anti-aquaporin-4 (AQP4) antibody-positive patients

Dosage and Administration

• PNH and aHUS: 600 mg IV weekly for first 4 weeks, then 900 mg IV every 2 weeks starting week 5
• gMG and NMOSD: 900 mg IV weekly for first 4 weeks, then 1200 mg IV every 2 weeks starting week 5

• Administer as intravenous infusion over 35 minutes
• Dilute to final concentration of 5 mg/mL in normal saline, 0.45% saline, or 0.9% saline
• Do not administer as IV push or bolus

• Renal impairment: No dosage adjustment required
• Hepatic impairment: No dosage adjustment required
• Pediatric patients: Safety and efficacy established for aHUS and PNH in children
• Elderly: No specific dosage adjustment recommended

Pharmacokinetics

Contraindications

• Patients with unresolved serious Neisseria meningitidis infection
• Patients not currently vaccinated against meningococcal disease (unless vaccination risks outweigh benefits)
• Hypersensitivity to eculizumab or any component of the formulation
• Patients with known hereditary fructose intolerance (contains sucrose)

Warnings and Precautions

• Increased risk of other serious infections, particularly encapsulated bacteria
• Monitoring for hemolysis with PNH discontinuation (risk of serious hemolysis)
• aHUS patients may experience thrombotic microangiopathy complications after discontinuation
• Infusion reactions, including anaphylaxis
• Patients may develop antibodies to eculizumab

Drug Interactions

• No formal drug interaction studies conducted
• Theoretical interactions with other complement inhibitors
• Caution with other immunosuppressive agents due to increased infection risk
• Live vaccines should be administered at least 4 weeks prior to initiation
• No known interactions with cytochrome P450 substrates

Adverse Effects

• Headache
• Nasopharyngitis
• Nausea
• Fatigue
• Back pain
• Cough

• Meningococcal infections (life-threatening)
• Other serious infections
• Infusion reactions
• Hypertension
• Leukopenia
• Thrombocytopenia
• Transaminase elevation

Monitoring Parameters

• Meningococcal vaccination status
• Baseline CBC with differential, LDH, haptoglobin, bilirubin
• Renal function tests (BUN, creatinine)
• Liver function tests

• Signs/symptoms of meningococcal infection (fever, headache, stiff neck, photophobia)
• CBC with reticulocyte count weekly for first 4 weeks, then monthly
• LDH, haptoglobin, bilirubin monthly
• Renal function monthly for aHUS patients
• Monitor for infusion reactions during administration

• Annual meningococcal vaccination booster
• Regular assessment for signs of infection
• Monitoring for hemolysis if considering discontinuation

Patient Education

• Understand the black box warning regarding meningococcal infection risk
• Recognize early signs of infection (fever, headache, stiff neck) and seek immediate medical attention
• Carry patient safety card at all times
• Complete required vaccinations before starting treatment
• Inform all healthcare providers about Soliris therapy
• Do not miss scheduled doses due to risk of breakthrough hemolysis
• Report any side effects, particularly infusion-related symptoms
• Understand the importance of compliance with monitoring appointments

References

1. Hillmen P, Young NS, Schubert J, et al. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2006;355(12):1233-1243. 2. Legendre CM, Licht C, Muus P, et al. Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome. N Engl J Med. 2013;368(23):2169-2181. 3. Howard JF Jr, Utsugisawa K, Benatar M, et al. Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalized myasthenia gravis (REGAIN): a phase 3, randomised, double-blind, placebo-controlled, multicentre study. Lancet Neurol. 2017;16(12):976-986. 4. Pittock SJ, Berthele A, Fujihara K, et al. Eculizumab in aquaporin-4-positive neuromyelitis optica spectrum disorder. N Engl J Med. 2019;381(7):614-625. 5. Soliris [package insert]. Boston, MA: Alexion Pharmaceuticals, Inc.; 2021. 6. Brodsky RA. Paroxysmal nocturnal hemoglobinuria. Blood. 2014;124(18):2804-2811. 7. Nester CM, Thomas CP. Atypical hemolytic uremic syndrome: what is it, how is it diagnosed, and how is it treated? Hematology Am Soc Hematol Educ Program. 2012;2012:617-625.