In some cases, information gained during developing a drug for one indication can be leveraged to support approval for a different indication. PNH (paroxysmal nocturnal hemoglobinuria) is a rare, progressive, and life-threatening disease. It is characterized by rampant destruction of red blood cells (hemolysis) and excessive blood clotting. Likewise, aHUS (atypical hemolytic uremic syndrome) is an ultra-rare genetic disease that causes abnormal blood clots to form in small blood vessels throughout the body. The sequelae of aHUS include kidney failure, damage to other organs, and premature death. There were no FDA-approved treatments for this rare disease.
Both aHUS and PNH are caused by chronic, uncontrolled activation of the complement system. During activation of the complement system, the terminal protein C5 is cleaved to C5a and C5b. C5a and C5b have been implicated in causing the terminal complement-mediated events that are characteristic of both aHUS and PNH. Eculizumab is a humanized monoclonal antibody (mAb) that binds C5, thereby inhibiting its cleavage. In 2007, Certara Strategic Consulting developed a PK/PD model model that supported the approval of this mAb for treatment of PNH based on evidence of effectiveness from clinical studies.