SOLIRIS (eculizumab): The first treatment specifically approved for PNH

For US Healthcare Professionals

Mechanism of Action

Unique mechanism of action leads to immediate and sustained reductions in hemolysis1,2

SOLIRIS® (eculizumab) specifically inhibits terminal complement1, which, in PNH patients, leads to chronic hemolysis and its debilitating consequences.3,4

In this MOA video, you will learn about:

  • Terminal complement activation and its association with chronic hemolysis in PNH
     
  • How SOLIRIS targets C5, the first component on the terminal complement pathway 1,2,5
     
  • The critical role that chronic hemolysis plays in PNH3,4,6,7
     
  • The effect of SOLIRIS on the debilitating signs, symptoms and consequences of PNH1,2,8

SOLIRIS specifically inhibits terminal complement activation

Mechanism of Action click to enlarge

 

SOLIRIS is a first-in-class, humanized, monoclonal antibody that targets the complement protein C5.1,2

  • C5 represents the point where pathways of complement activation converge5 to form C5a, a potent anaphylatoxin and C5b-9 (also known as the membrane attack complex or MAC, or terminal complement complex, TCC), which is responsible for destroying or lysing cells
     
  • SOLIRIS binds to C5 with high affinity to block the activation of terminal complement:
    • Inhibition of terminal complement leads to inactivation of one of its key functions, cell lysis, which is the cause of hemolysis in PNH

  • SOLIRIS preserves the proximal complement pathway defense mechanisms:
    • The proximal portion of the complement cascade generates complement proteins such as C3b, which actively assist with defense against microbes and clearance of immune complexes5,6

Next: Efficacy

IMPORTANT SAFETY INFORMATION

WARNING: SERIOUS MENINGOCOCCAL INFECTION

SOLIRIS® increases the risk of meningococcal infections.

Vaccinate patients with a meningococcal vaccine at least 2 weeks prior to receiving the first dose of SOLIRIS; revaccinate according to current medication guidelines for vaccine use.

Monitor patients for early signs of meningococcal infections, evaluate immediately if infection is suspected, and treat with antibiotics if necessary.

The effect of withdrawal of anticoagulant therapy during SOLIRIS treatment has not been established. Therefore, treatment with SOLIRIS should not alter anticoagulant management.

SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING INCLUDING WARNINGS, PRECAUTIONS, AND ADVERSE REACTIONS.

The most frequent adverse events observed in clinical studies were headache, nasopharyngitis, back pain, nausea, fatigue, and cough.

Please see important safety information (including boxed warning) as well as the complete prescribing information.

References:
1. Soliris® (eculizumab) prescribing information. Alexion Pharmaceuticals, Inc. 2007.
2. Data on File. Alexion Pharmaceuticals, Inc.
3. Parker C, Omine M, Richards S, et al. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood. 2005;106:3699-3709.
4. Johnson RJ, Hillmen P. Paroxysmal nocturnal hemoglobinuria: nature's gene therapy? J Clin Pathol Mol Pathol. 2992;55:145-152.
5. Hill A, Hillmen SJ, Elebute D, et al. Sustained response and long-term safety of eculizumab in paroxysmal nocturnal hemoglobinuria. Blood. 2005;106:2559-2565.
6. Rosse WF, Hillmen P, Schrieber AD. Immune-mediated hemolytic anemia. Hematology. (Am Soc Hematol Educ Program) January 2004:48-62.
7. Brodsky RA. Paroxysmal nocturnal hemoglobinuria. In: Hoffman R, Benz EJ, Shattil SJ, et al. eds. Hematology. 4th ed. Philadelphia, PA: Elsevier Churchill Livingstone. 2005:419-427.
8. Hillmen P, Young NS, Schubert J, et al. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2006;355:1233-1243.