Long-term Benefits of Ralinepag for PAH Patients Shown in Interim Data from Phase 2 Extension Trial

Long-term use of ralinepag, an investigational therapy being developed by Arena Pharmaceuticals, can promote positive changes in the outcome of patients with pulmonary arterial hypertension (PAH), interim data from a Phase 2 extension trial shows.

After taking oral ralinepag for a median of up to 1.8 years, patients continued to show significant improvements in their exercise capacity and blood flow in the lung arteries, compared with before the start of treatment.

“We are pleased with the long-term safety, tolerability and efficacy that ralinepag has demonstrated in the open-label extension of our Phase 2 trial,” Preston Klassen, MD, Arena’s executive vice president of research and development and chief medical officer, said in a press release. “This is the first time an oral prostacyclin has shown durable, long-term improvements on hemodynamic and functional measures.”

Ralinepag, formerly known as APD811, is a selective prostacyclin receptor agonist that acts as a strong vasodilator, widening blood vessels so that blood can flow easily through them. It can also prevent platelet clumping and inhibit overgrowth of blood vessel muscle cells, which can also have a negative impact on blood flow rate.

Previously, the company reported results from a 22-week Phase 2 trial (NCT02279160) in which 60 PAH patients were randomized to receive either ralinepag or a placebo. The data demonstrated that the investigational therapy could effectively reduce the risk of death, while improving blood flow in the lungs and enhancing patients’ exercise capacity.

Forty-five of the patients who completed the Phase 2 trial, of whom 30 were originally randomized to ralinepag and 15 to placebo, continued treatment with ralinepag beyond the 22-week period in the open-label extension of the study (NCT02279745).

Patients who had received ralinepag in both studies were treated for a median of 1.8 years in the open-label extension study, and those who switched from the placebo to the active therapy were treated for a median of 1.4 years.

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A comparison of physical capacity, determined by the six-minute walk distance (6MWD) test, and blood flow rate in the lungs, measured by the pulmonary vascular resistance (PVR) assessment, before and after treatment showed similar results in both groups of patients.

The 6MWD test revealed a mean improvement of 49.8 meters in the ralinepag-ralinepag group and 69.8 meters in the placebo-ralinepag group. PVR values also improved, showing a median reduction of 219 dyne-second/square centimeter (a measure of the blood’s viscosity) in the ralinepag-ralinepag group and 214 dyne-second/square centimeter in the placebo-ralinepag group, compared with initial values before treatment.

“Patients continuing ralinepag from the original study clearly maintained improvements in PVR and 6MWD. Those patients switching from placebo to ralinepag in this extension trial demonstrated a similar magnitude of effect on PVR and 6MWD,” Klassen said.

“These data reinforce our belief that PAH patients can truly benefit from ralinepag’s improved receptor potency and extended pharmacokinetics,” Klassen added. “Ralinepag has the potential to offer the pharmacokinetic and pharmacodynamic advantages of continuously infused IV [intravenous] prostacyclin with the ease of a once-daily oral tablet.”

The safety profile of the investigational treatment during the open-label trial extension was similar to that reported in the Phase 2 trial, and that of other prostacyclin therapies for PAH management. The most common adverse events reported were headache and nausea.

Notably, during the extension period, the frequency of adverse events was lower than in the Phase 2 trial, suggesting improved tolerability to the treatment compared with the initial dosing period.

The company is currently recruiting participants for a Phase 3 trial (NCT03626688) that will further evaluate ralinepag’s effectiveness and safety in treating PAH. The study is expected to enroll about 700 adults with symptomatic PAH (WHO functional class 2 to 4) at clinical centers across the U.S. For more information on study locations and contacts, visit this link.

“It is encouraging to gain additional insight into the long-term safety and efficacy of ralinepag. I look forward to seeing data from the Phase 3 ADVANCE program and the effect that ralinepag may have when added to PAH standard of care,” said Vallerie McLaughlin, MD, the Kim A. Eagle MD Endowed Professor of Cardiovascular Medicine at the University of Michigan and director of the Pulmonary Hypertension Program.

“These data validate progress towards bringing a new therapeutic option to patients suffering from PAH, a devastating disease with significant unmet medical need despite available treatments,” she said.