Drug for rare blood disorder gets EU orphan status

A DRUG for rare blood disorder developed at Penn Medicine has this week received orphan drug status in the European Union. The compound, called AMY-101, is used 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.

The designation will allow Amyndas, the company currently developing the AMY-101, to proceed with expedited clinical development, since 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.

AMY-101 could turn out to be less costly and more effective for the majority of patients with this rare blood disorder. Currently, PNH is 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”, which is a network of more than 50 proteins in the blood and on cell surfaces. Part of the innate immune system, complement quietly cruises the body, keeping a low profile until triggered into action; however, this defense system can also be inappropriately activated and attack cells, contributing to a broad spectrum of immune, inflammatory, and age-related diseases.

Despite current treatment for PNH, one third of patients continue to require blood transfusions to manage their anemia. This non-response is due to fragments of complement C3 proteins on the surface of their red blood cells, which are eventually attacked by immune cells. AMY-101, on the other hand, tames this inappropriate complement activation and protects cell surfaces from attack.

John Lambris, PhD, developed AMY-101 at Penn and the university licensed it to Amyndas, which is now further developing the compound for application in the clinic. Dr Lambris is the Dr. Ralph and Sallie Weaver Professor of Research Medicine in the Department of Pathology and Laboratory Medicine in the Perelman School of Medicine. He is also founder and equity holder of Amyndas Pharmaceuticals, which has exclusively licensed the AMY-101 technologies from Penn and is developing complement inhibitors for clinical applications, but will have no direct involvement with the conduct of clinical trials.

Dr Lambris and colleagues harnessed the idea that inhibition of the complement cascade using small inhibitory molecules like AMY-101 would be a better strategy to prevent hemolysis and immune cell recognition while being potentially more cost-effective. The team investigated the effect of AMY-101 on self attack and resulting hemolysis using human PNH cells, and found it be active.