Pharming receives Orphan Drug Designation from the European Commission for leniolisib for the treatment of activated phosphoinositide 3-kinase delta syndrome (APDS) - Seite 2

APDS is defined as an ultra-rare, genetic, primary immunodeficiency disease characterized by increased susceptibility to recurrent and/or severe bacterial and viral infections, chronic benign lymphoproliferation, and/or autoimmune disease. The APDS incidence rate around the world is currently estimated to be 1-2 per million. The diagnosis of APDS is made by sequencing the genes PIK3CD and/or PIK3R1 in patients with a compatible phenotype, i.e., immunodeficiency and lymphoproliferation of unknown origin.

Beginning in childhood, people with APDS develop recurrent infections, particularly in the lungs, sinuses, and ears. Over time, recurrent respiratory tract infections can lead to a condition called bronchiectasis, which damages the passages leading from the windpipe to the lungs (bronchi) and can cause breathing problems. People with APDS may also have chronic active viral infections, commonly Epstein-Barr virus or cytomegalovirus infections. Sufferers also frequently develop lymphomas and other cancers.

Another possible feature of APDS is abnormal clumping of white blood cells. These clumps can lead to enlarged lymph nodes (lymphadenopathy), or the white blood cells can build up to form solid masses (nodular lymphoid hyperplasia), usually in the moist lining of the airways or intestines. While lymphadenopathy and nodular lymphoid hyperplasia are noncancerous (benign), APDS also increases the risk of developing a form of cancer called B-cell lymphoma. 

About leniolisib

Leniolisib is a small molecule phosphoinositide 3-kinase delta (PI3Kẟ) inhibitor with immunomodulating and potentially anti-neoplastic activities. Leniolisib inhibits the production of phosphatidylinositol-3-4-5-trisphosphate (PIP3). PIP3 serves as an important cellular messenger specifically activating Akt (via PDK1) and regulates a multitude of cell functions such as proliferation, differentiation, cytokine production, cell survival, angiogenesis, and metabolism. Unlike PI3Kα and PI3Kβ which are ubiquitously expressed, PI3Kẟ and PI3Kγ are expressed primarily in cells that are of hematopoietic origin. The central role of PI3Kẟ in regulating numerous function of cells of the adaptive immune system (B-cells and to a lesser extent T cells) as well as the innate immune system (neutrophil, mast cells, and macrophages) strongly indicates that PI3Kẟ is a valid and potentially effective therapeutic target for APDS.