Eiger BioPharmaceuticals will discontinue the development of ubenimex as a therapy for pulmonary arterial hypertension (PAH) due to disappointing results in the Phase 2 LIBERTY clinical trial. The treatment failed to improve PAH patients’ pulmonary vascular resistance or exercise capacity.
Ubenimex (sold in Japan as Bestatin) is a small-molecule inhibitor of arginyl aminopeptidase and leukotriene A₄ hydrolase. The treatment blocks the production of leukotriene B4 (LTB4), a naturally occurring inflammatory mediator involved in tissue damage and PAH-associated blood vessel remodeling.
Research has shown that LTB4 levels are elevated in animal models of PAH, causing constriction of blood vessels and high blood pressure, and that blocking LTB4 activity reduces the obstruction of blood vessels and increases overall survival.
The phase 2 LIBERTY clinical trial (NCT02664558) is a multi-center, double-blind study assessing ubenimex’s efficacy in improving exercise capacity and slow clinical deterioration in adult PAH patients with mild to marked limitations in activity. A total of 61 participants were enrolled and randomly assigned to ubenimex or placebo treatments, starting in July 2016.
Efficacy results showed no improvement in either pulmonary vascular resistance (the trial’s primary endpoint) or exercise capacity, as measured through the 6-minute walk distance test (the trial’s secondary endpoint).
Treatment with ubenimex did not lead to safety concerns.
Although researchers are still analyzing the data obtained, based on the results Eiger decided to discontinue the development of ubenimex as a PAH therapy.
“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.
Ubenimex had been designated an Orphan Drug for PAH by both the U.S. Food and Drug Administration and the European Medicines Agency (EMA).
The company will continue the development of ubenimex for lymphedema, a condition characterized by swelling in arms and/or legs due to accumulation of lymph. The treatment is currently being tested in the multi-center ULTRA phase 2 study (NCT02700529). Results are expected in the second half of 2018.
In addition, Eiger is conducting phase 2 clinical studies to develop therapies for patients with chronic hepatitis delta (NCT02765802) and post-bariatric hypoglycemia (NCT03373435), which can develop following bariatric surgery for weight loss.