United Therapeutics Ends Clinical Development of Esuberaprost as Add-on Therapy for PAH

United Therapeutics announced it has ended its Phase 3 BEAT trial testing esuberaprost as an add-on therapy to its product Tyvaso (inhaled treprostinil) for clinically symptomatic patients with pulmonary arterial hypertension (PAH).

According to a company press release, the study failed to reach its main endpoint of delaying the time to first clinical worsening events.

Esuberaprost, also called beraprost sodium 314d modified release or BPS-314d-MR, was developed by Lung Biotechnology, a wholly-owned subsidiary of United Therapeutics.

Esuberaprost worked by mimicking the action of prostacyclin, a molecule naturally produced by the body that dilates blood vessels (a vasodilator). Prostacyclin is found at abnormally low levels in PAH patients, which is thought to contribute to the development of the disease. Prostacyclin also stops platelets (a type of blood cell involved in clotting) from clumping together and potentially blocking arteries.

The pharmacologic action of esuberaprost was mediated by specifically binding to PGI2 receptors in smooth muscle cells (the blood vessel’s endothelium) and platelets. Upon binding, the compound widened blood vessels, preventing the formation of blood clots, and lowering blood pressure in the lungs. As a result, it was expected to improve the symptoms of PAH.

The modified release formulation of the therapy was designed to promote the release of the therapeutic agent over several hours, reducing the need for frequent administrations and making it more convenient to use.

The BEAT study (NCT01908699) was set to recruit 240 patients with PAH, across 75 clinical sites in the U.S. and Israel. Participants were randomized to receive esuberaprost, administered as one or two oral tablets four times daily, or to a placebo given in the same dose.

All patients were taking Tyvaso before the trial. Patients not on Tyvaso received the therapy over a period of 90 days before study enrollment.

The active component of Tyvaso, developed and marketed by United Therapeutics, is a synthetic substance that mimics the action of prostacyclin. By binding to receptors on the cells of arterial walls, Tyvaso triggers the relaxing of arterial wall muscles, making it easier for blood to be pumped through the lungs, and increasing oxygen transport throughout the body.

The BEAT study’s main goal was to assess whether adding esuberaprost to Tyvaso would delay clinical worsening events, including death, hospitalization, and disease progression.

Based on BEAT’s failure to reach its primary endpoint, United Therapeutics decided to discontinue further esuberaprost development.