A Penn Medicine-developed drug has received orphan status in Europe this week for the treatment of paroxysmal nocturnal hemoglobinuria (PNH), a rare, life-threatening disease that causes anemia due to destruction of red blood cells and thrombosis. Orphan status brings such benefits as tax incentives, market exclusivity for 10 years, possibilities for additional research funding, and additional guidance from the European Medicines Agency during clinical development. This designation for the compound, called AMY-101, will allow Amyndas, the company currently developing the compound, to proceed with expedited clinical development. 

AMY-101 is a new way to fight PNH, which is currently only treatable with the most expensive drug available for sale in the United States. The new strategy is based on inhibiting C3, a central component of the oldest part of the human immune system – called “complement” -- and could turn out to be less costly and more effective for the majority of patients with this rare blood disorder.

Complement is a network of more than 50 proteins in the blood and on cell surfaces, part of the innate immune system, that quietly cruise the body, keeping a low profile until triggered into action. But this defense system can also be inappropriately activated and attack cells, contributing to a broad spectrum of immune, inflammatory, and age-related diseases.

John Lambris, PhD, the Dr. Ralph and Sallie Weaver Professor of Research Medicinein the Department of Pathology and Laboratory Medicine in the Perelman School of Medicine, studies this early-warning system and how to correct it when its response goes overboard. Lambris developed AMY-101 at Penn and the university licensed it to Amyndas, which is now further developing the compound for application in the clinic.

PNH affects between 1 and 5 per million people and is caused by a defective expression of regulatory proteins on the surface of blood cells, leaving them vulnerable to complement attack. This can lead to premature death of the red blood cells, a process called hemolysis, which results in severe anemia and contributes to a high risk of clotting. AMY-101 tames this inappropriate complement activation and protects cell surfaces from attack.

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