A novel compound has received orphan status in the Europe Union to treat paroxysmal nocturnal hemoglobinuria (PNH), a life-threatening disease that causes severe anemia and confers a high risk of thrombosis.
The compound, AMY-101, works by inhibiting C3, a central component of the complement immune system.
AMY-101 was developed by John Lambris, PhD, of the University of Pennsylvania, and subsequently licensed to Amyndas Pharmaceuticals.
AMY-101’s orphan status provides Amyndas with benefits such as tax incentives, market exclusivity for 10 years, possibilities for additional research funding, and additional guidance from the European Medicines Agency during clinical development.
How AMY-101 works
PNH is caused by the defective expression of regulatory proteins on the surface of blood cells, which leaves them vulnerable to complement attack. This can lead to hemolysis, which results in severe anemia and contributes to a high risk of thrombosis.
The monoclonal antibody eculizumab is often successful in treating PNH, but roughly a third of patients do not respond well to the drug and still require blood transfusions to manage their anemia.
Research has suggested this lack of response is due to fragments of complement C3 proteins on the surface of the patients’ red blood cells, which are eventually attacked by immune cells.
In an attempt to overcome this problem, Dr Lambris and his colleagues developed AMY-101. The drug is designed to inhibit the complement cascade, thereby preventing hemolysis and immune cell recognition.
The researchers have investigated the effects of AMY-101 on self-attack and the resulting hemolysis in human PNH cells and found the drug to be active.
These results have not been published, but the group has published results with a C3 inhibitor known as Cp40, and AMY-101 is based on Cp40.
The researchers reported in Blood that Cp40 and its long-acting form, PEG-Cp40, effectively inhibited hemolysis and efficiently prevented the deposition of C3 fragments on red blood cells from patients with PNH.
