Novel PAH Drug to Be Tested in Clinical Trial

Novel PAH Drug to Be Tested in Clinical Trial

Eiger BioPharmaceuticals, Inc., a clinical-stage biopharmaceutical company committed to bringing to market novel products for the treatment of orphan diseases, recently announced that it has completed a license agreement with Nippon Kayaku Co., Ltd., in Tokyo, Japan, to develop Bestatin™ (ubenimex) for the treatment of Pulmonary Arterial Hypertension (PAH) and other inflammatory diseases by implicating the leukotriene B4 (LTB4) enzyme.

Bestatin is an oral, competitive, reversible protease inhibitor of the leukotriene A4 hydrolase (LTA4H), an enzyme that converts LTA4 to LTB4 — an inflammatory mediator that occurs naturally.  Nippon Kayaku has marketed Bestatin in Japan for more than 25 years for a different clinical indication.

In a study recently published in the journal Science Translational Medicine, a team of researchers from Stanford University was able to determine that LTA4 and LTB4 hydrolase are increased in PAH animal models as well as in humans with PAH.  Increased LTB4 was found to cause inflammation, which led to arteriole occlusion as well as hypertension in PAH animal models.

Results from the study revealed that pharmacologically targeting the inhibition of LTB4, incorporating Bestatin, resulted in the reversion of PAH in those animals that were treated with the composite. The data also showed that the treatment results in the opening of the obstructed arterioles, an improvement in the cardiac function, and in the survival of the animals.  Based on the results, Bestatin is now a potential therapeutic candidate to treat PAH where pathological inflammation is thought to be critical in the disease etiology.

“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,” said David Cory, President and CEO of Eiger in a recent press release.  “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.”

“We are pleased to enter into this agreement with Eiger BioPharmaceuticals and establish a path for Bestatin to be studied in PAH,” said Yoshihiro Nambu, MD, PhD, Head of Pharmaceuticals Group, Nippon Kayaku. “Bestatin is a well-characterized drug with a long history of use in Japan.  PAH is a debilitating, progressive disease and there is no approved disease modifying therapy.  It will be exciting to assess the impact of targeted inhibition of LTB4 production with Bestatin in PAH disease.”

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