Eiger BioPharmaceuticals, Inc., a clinical-stage biopharmaceutical company that develops and commercializes drugs for the treatment of orphan diseases and conditions with ineffective current treatments, announced a new license agreement with a leading Japanese pharmaceutical company, Nippon Kayaku. Eiger BioPharmaceuticals aims to develop Nippon Kayaku’s therapeutic drug Bestatin™ (ubenimex) for the treatment of pulmonary arterial hypertension (PAH) and other inflammatory diseases involving the same molecular pathway.
Bestatin is an oral small molecule drug that inhibits aminopeptidase and leukotriene A4 hydrolase (LTA4H). LTA4H is an enzyme responsible for the conversion of leukotriene A4 into leukotriene B4 (LTB4), a mediator involved in the inflammatory response and responsible for activation of leukocytes, recruitment of neutrophils, immune cells that exacerbate the inflammation onset, and production of reactive oxygen species. Bestatin is not approved for any treatment in Europe or the U.S., but it is approved in Japan as an adjunct treatment to chemotherapy, maintaining remission and survival in acute non-lymphocytic leukemia in adult patients.
Eiger’s future development of the drug for PAH stems from a Stanford University research study where blocking of LTA4H by inhibitory agents such as Bestatin led to reduction of LTB4 levels and reversion of PAH in animal models. The study, entitled “Blocking Macrophage Leukotriene B4 Prevents Endothelial Injury and Reverses Pulmonary Hypertension,” was published Science Translational Medicine. The researchers showed that, in both animal models of PAH and human PAH, there is an accumulation of macrophages near the lung arterioles. These cells produce high levels of LTA4H. The resulting production of LTB4 leads to apoptosis of pulmonary artery endothelial cells, exaggerated proliferation of pulmonary artery smooth muscle cells and inflammation — all essential to the pathogenesis of PAH. These observations in human tissues and the inhibition effects observed in the animal models lead researchers to believe that Bestatin might constitute an effective and promising therapy candidate for human PAH disease treatment.
David Cory, President and CEO of Eiger, in a press release on the importance of finding and approving a disease modifying therapy for PAH, said: “Approved treatments for PAH work primarily by vasodilation of pulmonary arteries. No approved therapy for PAH has been shown to reverse inflammation or modify disease. Recently published results of studies conducted at Stanford University suggest that elevated LTB4 may play a role in the inflammatory component of PAH disease. These results suggest a potential for disease modification by targeting inflammation via inhibition of LTB4 production. Our partnership with Nippon Kayaku and access to Bestatin, a well-characterized, commercially available drug in Japan, allows us to prepare for a clinical study in patients with PAH. The US IND is already approved. Enrollment is scheduled to begin in early 2016.”
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