Eculizumab

Eculizumab is approved under the name ^Soliris® for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH). Paroxysmal nocturnal hemoglobinuria is a rare, life-threatening condition in which there is a very rapid breakdown of red blood cells. This leads to anemia, thrombosis and dark urine. Eculizumab is also approved for the treatment of atypical hemolytic uremic syndrome (aHUS). The enormous annual therapy costs are 600,000€ (!).

Eculizumab binds to the protein C5 of the complement system and blocks the so-called terminal activation. This reduces the destruction of erythrocytes and improves the symptoms of the disease. In patients with paroxysmal nocturnal haemoglobinuria, some of the erythrocytes show a defect of surface proteins (e.g. the protein CD59), which are connected to the cell membrane by special anchor molecules (glycosylphosphatidylinositol (GPI) anchors). CD59 prevents the complement system from attacking the erythrocytes. Defects in this surface protein of the erythrocytes lead to their premature destruction.

Since an important part of the complement cascade is blocked under eculizumab, an increased sensitivity to bacterial infections must be expected (e.g. infections with capsule-forming bacteria such as meningococci and gonococci). In this respect, appropriate measures must be taken(vaccination against Neisseria meningitidis).

Other side effects: The most common side effects with eculizumab include infections (urinary tract infections, upper respiratory tract infections, nasal and pharyngitis). Furthermore, dizziness, headache, back and joint pain, fever, hematoma formation.

Soliris®

Eculizumab is being tested in a clinical trial against dermato (poly)myositis. Furthermore, the compound is used in membranoproliferative glomerulonephritis.

Eculizumab showed a positive effect on intestinal perforation in individual cases of Köhlmeier-Degos disease.

1. Moghadam-Kia S et al (2017) Modern Therapies for Idiopathic Inflammatory Myopathies (IIMs): Role of Biologics. Clin Rev Allergy Immunol 52:81-87.