Eiger BioPharmaceuticals has dosed the first patient in its Phase 2 LIBERTY study with the company’s product candidate ubenimex (Bestatin). The trial will assess Bestatin’s effects when added to standard of care treatment in people suffering from pulmonary arterial hypertension (PAH).
Even though there are several approved vasodilator therapies, PAH is still a significant threat to the lives of those suffering from this progressive, cardiovascular disease.
Bestatin is a well-characterized small-molecule inhibitor of leukotriene A4 hydrolase (LTA4H) – a compound that blocks the production of leukotriene B4 (LTB4), an inflammatory mediator playing a specific role in the development of PAH.
LTB4 is a naturally-occurring inflammatory mediator known to be elevated in animal and human models of PAH. In animal models, elevated LTB4 levels have been shown to lead to inflammation, causing arteriole occlusion, vasoconstriction and hypertension. Targeted pharmacologic inhibition of LTB4 reversed PAH disease in animals, as demonstrated by a reduced obstruction of arterioles, improved cardiac function, and overall survival.
“While vasoactive agents have utility in the clinical management of the symptoms of PAH, they do not address the underlying inflammation, which is an important signature of this cardiovascular disease,” Dr. Roham Zamanian, MD, the trial’s lead investigator and director of the Adult Pulmonary Hypertension Program at Stanford University School of Medicine, said in a press release.
He said investigators “may have a chance to realize a potentially disease modifying approach.”
LIBERTY is a multi-site, randomized, double-blind, placebo-controlled Phase 2 trial assessing Bestatin in PAH patients. About 45 people will receive either Bestatin or a placebo in a randomized assortment for 24 weeks.
Those who finish all 24 weeks of treatment will be eligible to enroll in an open-label extension study (LIBERTY2) to receive additional treatment with Bestatin. The extension study will allow patients to choose to receive Bestatin for at least 24 more weeks, and will provide complementary data on the safety, tolerability, and efficacy of the drug candidate.
“The goal of the LIBERTY study is to block LTB4 production with ubenimex as a novel and potentially disease modifying treatment for PAH,” said Dr. Joanne Quan, MD, Eiger’s chief medical officer.
“Inflammation, now recognized as an important component of PAH, is not addressed by currently available therapies,” she said, adding that recently published preclinical studies from Stanford suggest that elevated LTB4 levels may play a role in the inflammatory component of PAH.
“Targeted LTB4 blockade may represent an important new therapeutic approach to this disease,” she added.
Bestatin has been granted orphan drug designation for PAH by the U.S. Food and Drug Administration (FDA) and by the European Medicines Agency (EMA). It has not been approved for any indication in either the U.S. or Europe.