Arena Pharmaceuticals, United Therapeutics Reach Global Licensing Agreement for Ralinepag

Arena Pharmaceuticals and United Therapeutics have reached a global licensing agreement for the pulmonary arterial hypertension (PAH) therapy candidate ralinepag.

Ralinepag (APD811) is a next-generation, selective prostacyclin receptor agonist designed for oral delivery. Prostacyclin, produced by cells lining the walls of blood vessels, is a vasodilator (a widener of blood vessels), anti-inflammatory, and a platelet aggregation inhibitor. It also inhibits the proliferation of vascular smooth muscle cells in blood vessels.

According to Arena, ralinepag has an extended half-life, referring to the time required for a compound in the body to be reduced by half, an indicator of how long it has an effect.

Under the terms of the agreement, United will obtain exclusive, worldwide rights from Arena to develop, manufacture, and market ralinepag. In return, Arena will receive up to $1.2 billion, which includes an upfront payment of $800 million and potential milestone payments of up to $400 million. Arena also will receive royalties on ralinepag’s annual net sales.

The agreement will take effect at the end of a required waiting period.

Arena recently hosted a conference call and live webcast about the agreement, which can be viewed at the company’s website.

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“We believe ralinepag has the potential to transform the treatment of PAH,” Amit D. Munshi, Arena’s president and CEO, said in a press release. “We are thrilled to partner with United Therapeutics, based on their long-standing, deep commitment to the PAH community. This transaction represents a significant milestone in the development of ralinepag.”

Martine Rothblatt, PhD, United’s chairman and CEO, added: “We are very impressed with the clinical development plan and [the U.S. Food and Drug Administration’s] coordination being managed by Arena.”

Rothblatt also noted that United had applied its “two decades of knowledge about PAH” in conducting due diligence on ralinepag, and the company remains confident that after “FDA approval via at least one of its several different potential regulatory pathways,” the therapy “will help greater than 10,000 patients annually from the 2020s and well into the 2030s.”

A Phase 3 trial (NCT03626688) named Advance Outcomes is currently evaluating the efficacy and safety of adding ralinepag to standard of care or PAH-specific background therapy in patients with group 1 PAH, according to the World Health Organization. This study is currently recruiting participants in the U.S. More information on study locations and contacts can be found here.

In April, results from a 13-week Phase 2 study (NCT02279160) in 60 patients with PAH showed that ralinepag lowered the risk of death. Key findings presented in late 2017 included improved blood flood in lung arteries and greater exercise capacity.

Recently, Arena presented Phase 1 results showing that an extended-release tablet of ralinepag had a superior pharmacokinetic profile compared to immediate-release ralinepag capsules and the approved immediate-release medication Uptravi (selexipag), marketed by Actelion Pharmaceuticals. The pharmacokinetic profile refers to how a compound is absorbed, distributed, metabolized, and excreted in the body.

Arena’s CEO also emphasized that the agreement will enable Arena to pursue development of its best-in-class product pipeline, led by etrasimod. A Phase 3 program with etrasimod is expected to start soon for ulcerative colitis and Crohn’s disease, two forms of inflammatory bowel disease. Arena also is developing olorinab, a treatment candidate for visceral pain associated with gastrointestinal diseases, including Crohn’s disease.