Initiated in 2016, the LIBERTY trial (NCT02664558) included 61 patients with diagnosed WHO Group 1 PAH across 45 clinical sites in the United States and Canada. Participants were randomized to receive 150 mg of ubenimex or placebo three times a day for up to 24 weeks.
The treatment failed to significantly improve pulmonary vascular resistance in comparison to placebo, which was the primary goal of the study. In addition, ubenimex also was unable to improve exercise capacity of the patients as determined by the 6-minute walk distance (6MWD) test, the secondary goal of the study.
Based on these negative results, the company announced it will discontinue clinical development of ubenimex for the treatment of patients with PAH.
“While we are disappointed with results from the LIBERTY study, we have always recognized that PAH is a complex disease and that this was a translational program,” David Cory, president and CEO at Eiger, said in a press release.
Eiger, however, is going to continue the development of ubenimex as an investigative therapy for the treatment of lymphedema, a condition characterized by the accumulation of fluids due to damage to lymphatic vessels. The safety and effectiveness of ubenimex in adult patients with lymphedema is currently being evaluated in the Phase 2 clinical trial ULTRA (NCT02700529).
Ubenimex is a small-molecule that has the potential to prevent the activity of aminopeptidases and leukotriene A4 hydrolase (LTA4H). Its inhibitory effect has demonstrated it can regulate the response of immune cells, and manage pro-inflammatory signals important for vessels dilation, as well as promote the formation of new lymphatic vessels.
The inhibitor was approved in Japan, under the brand name Bestatin, as an add-on immunotherapy to standard chemotherapy for remission maintenance and to extend survival of adult patients with acute non-lymphocytic leukemia.
Ubenimex was granted orphan drug designation for PAH by the U.S. Food and Drug Administration (FDA) and by the European Medicines Agency (EMA), but never has been approved for any indication in either the U.S. or Europe.