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A Proof of Concept Study of LTB4 Inhibition in Patients with Pulmonary Arterial Hypertension (WHO Group 1) (LIBERTY)?

Roham Zamanian

Erica McCluskey

Tristen Moors

Joanne Quan

Mark Nicolls


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Conference: 2017 PH Professional Network Symposium

Release Date: 10.06.2017

Presentation Type: Abstracts

File Download: 2017 PHPN Abstract 1020

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Abstract presented at the 2017 PH Professional Network Symposium held in Bethesda, MD on October 5-7, 2017


To conduct a clinical proof of concept study to test the role of inhibition of leukotriene B4 (LTB4) in patients with pulmonary arterial hypertension (PAH) WHO Group 1.


Pulmonary Arterial Hypertension is a progressive and life-threatening disease characterized by increased pulmonary vascular resistance, heart failure, and premature death. Although management of PAH has improved significantly with the development of multiple drugs targeted on 3 pathways, the mortality rate remains high, with a life expectancy of 7 years after diagnosis (McGoon 2014). Thus, new approaches are needed, and approaches which may modify disease progression.

Ubenimex is an oral, small molecule inhibitor of both leukotriene A4 hydrolase (LTA4H) and aminopeptidase. Animal models demonstrate that inhibition of LTB4 ameliorates ¬¬¬¬¬multiple manifestations of pulmonary vascular disease (Tian et al, 2013). A prominent pathological feature of PAH is accumulation of macrophages near the arterioles of the lung. In both rat models of PAH and human PAH lung tissue, accumulated macrophages expressed high levels of LTA4H, the enzyme that converts leukotriene A4 (LTA4) to leukotriene B4 (LTB4). In addition, elevated levels of LTB4 are seen in some patients with PAH. These data suggest that LTB4 may be important in patients with WHO Group 1 PAH, and inhibition of LTB4 may be a novel therapeutic approach to treatment of PAH.


We designed a Phase 2, multicenter, randomized, double-blind, placebo-controlled, parallel-group study in patients with PAH (WHO Group 1). The study was conducted at multiple sites in North America. Patients were randomized in a 2:1 ratio to receive 150 mg TID of ubenimex or matching placebo, administered orally for a total of 24 weeks. All approved PAH specific drugs were allowed as background therapy, and at least one background drug was required. Patients who complete the randomized, double-blind study may be eligible to enroll in an open-label extension study.


We describe the key eligibility criteria and enrollment of a proof of concept study enrolled entirely in North America.


Sixty-one PAH patients were enrolled in a 10-month period across 45 clinical sites in the United States and Canada.