1st Patient Dosed in Phase 2 Study of Ubenimex as Add-on PAH Therapy

Eiger BioPharmaceuticals recently reported the dosing of a first patient in its Phase 2 LIBERTY clinical trial, evaluating the effects of ubenimex (Bestatin) as an add-on therapy to current standard of care in patients with pulmonary arterial hypertension (PAH). The study is currently recruiting adult patients with PAH WHO Group 1.

Ubenimex is a small molecule able to inhibit the activity of the enzyme LTA₄H, which is involved in the formation of the proinflammatory mediator LTB4. Evidence from recent studies suggest that high levels of LTB4 play a role in the inflammatory process of PAH.

LIBERTY (NCT02664558) is a randomized, double-blind and placebo-controlled study evaluating the efficacy, safety, and tolerability of ubenimex in about 45 patients with a clinical PAH diagnosis. Patients enrolled will receive ubenimex or a placebo plus standard care for 24 weeks, and all those who complete the treatment can choose to participate in an open-label extension trial and receive ubenimex for at least another 24 weeks.

“The LIBERTY study represents a transformative, clinical translational effort with potential to demonstrate, for the first time, disease modification in PAH,” said Roham Zamanian, MD, lead investigator and director of the Adult Pulmonary Hypertension Program at Stanford University School of Medicine, in a press release. “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. We have arrived at a moment of shift of therapeutic paradigm, where we may have a chance to realize a potentially disease modifying approach.”

Stanford’s Medical Center in California is one of two sites currently recruiting patients for the trial; the other is Inova Fairfax Medical Campus in Virginia.

“The goal of the LIBERTY study is to block LTB₄ production with ubenimex as a novel and potentially disease modifying treatment for PAH,” said Joanne Quan, MD, chief medical officer at Eiger BioPharmaceuticals. “Inflammation, now recognized as an important component of PAH, is not addressed by currently available therapies. Recently published preclinical results of studies conducted at Stanford University suggest that elevated LTB₄ levels may play a role in the inflammatory component of PAH, which can lead to obstructed arterioles, vasoconstriction, and worsening cardiac function. Targeted LTB₄ blockade may represent an important new therapeutic approach to this disease.”

For more information about the trial, including how to participate, please visit this link.

PAH is an increase of blood pressure in the pulmonary artery, pulmonary vein, or pulmonary capillaries, together known as the lung vasculature, leading to shortness of breath, dizziness, fainting, leg swelling and other symptoms. As the disease progresses, the effort that the heart has to make to pump blood through the arteries increases, weakening the muscle and leading to heart failure.