Development
Since Alexion's founding in 1992, the company's research efforts have focused primarily
on
complement inhibition – the selective blocking of the complement cascade.
In 2007, Alexion became the first company to discover, develop and successfully
commercialize a terminal complement inhibitor.
The
complement cascade consists of a series of proteins that form an important
component of the immune system, but when unregulated can cause harmful inflammation
and numerous clinical consequences if inappropriately activated.25 Naturally-occurring
but highly specialized proteins are designed to ensure that the complement system
does not get out of control, and these proteins are vital to prevent potentially
harmful effects. In some life-threatening diseases, the absence of these specialized
regulatory or protective proteins lead to severe clinical disorders.
Based on research conducted in the 1980s and early 1990s, researchers at Alexion
believed that selective targeting of the complement system was the key to treating
certain autoimmune and inflammatory diseases. In the design of the complement inhibitor
Soliris, complement protein C5 was identified as the most appropriate protein to
block in the complement pathway, because it is common to all activation pathways
of the complement system. Blockade at C5 also preserves critical protective functions
of the complement system while preventing the generation of the activation products
C5a and C5b-9 which cause inflammation and destruction of cells and tissues.23
In 2002 the company began to focus on the treatment of patients with paroxysmal
nocturnal hemoglobinuria (PNH). PNH is a rare and life-threatening blood disorder
characterized by complement-mediated hemolysis, the destruction of a person's red
blood cells, due to absence of a complement inhibitor.7 In patients with
PNH, hemolysis can cause thromboses (blood clots), kidney disease, liver failure,
disabling fatigue, impaired quality of life, recurrent pain, shortness of breath,
increased pressure in the blood vessels of the lungs, intermittent episodes of dark
colored urine (hemoglobinuria), and anemia.2,4,6,8
In May 2002 the first patient with PNH was dosed with Soliris in an 11-patient,
open-label pilot study to test the efficacy and safety of Soliris as a treatment
for PNH. The PNH clinical studies demonstrated that Soliris reduced hemolysis in
every treated patient and led to positive outcomes for patients suffering from PNH.
This data is the basis for regulatory approval of Soliris for the treatment of patients
with PNH in both the United States and European Union in 2007.23