Paroxysmal nocturnal hemoglobinuria (PNH) is a rare bone marrow failure disorder. It manifests with hemolytic anemia, thrombosis, and peripheral blood cytopenias. Destruction of red blood cells by the complement system (an important innate immune system in humans and animals) is characteristic of the disease. Complement factor D is a serine protease, involved in the alternative complement pathway of the complement system. Indeed, the factor plays an essential role in the alternative complement pathway (AP) initiated complement component (C3) convertase formation, as well as the amplification loop of the complement cascade. Therefore, complement factor D becomes the target for the treatment of AP-related disease. Inhibition of the complement factor D can prevent both intravascular and extravascular hemolysis in PNH.

Following research, Pelecopan (BCX9930) (HY-147297) exhibits highly potent inhibitory activity against sterolytic activity of purified human complement factor D with an IC₅₀ of 14.3 nM. Pelecopan also inhibits proteolytic activity of complement factor D against factor B bound to C3b, as well as AP-mediated hemolysis of rabbit erythrocytes (IC₅₀=28.1 and 29.5 nM, respectively). Furthermore, Pelecopan suppresses C3 fragment deposition on PNH erythrocytes (IC₅₀=39.3 nM). Meanwhile, it does not inhibit the enzyme activity of the human serine proteases thrombin, activated protein C, tissue plasminogen activator, and trypsin (IC₅₀: >28 μM); either activated factor X or activated factor XII (IC₅₀: >50 μM). Moreover, Pelecopan (100 and 200 mg; PO; twice daily) completely suppresses AP activity of serum in rhesus monkeys.

In conclusion, Pelecopan is a potent, selective, and orally active complement factor D inhibitor, possessing the potential to study PNH.