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Ralinepag improves pulmonary vascular resistance in PAH
Patients with pulmonary artery hypertension who were treated with ralinepag in addition to single or dual background therapy had improved pulmonary vascular resistance compared with those treated with placebo, according to data presented at the CHEST annual meeting.
“It was ... a clinically meaningful effect that portends an improvement through something that would correspond in most cases with an improvement in terms of their symptoms, but more importantly in terms of their long-term outcomes,” Vallerie V. McLaughlin, MD, professor at University of Michigan Medical School in Ann Arbor, told Cardiology Today.
Researchers reviewed data from patients who had stable functional class II to IV PAH, achieved a 6-minute walk distance between 100 m and 500 m and were taking background PAH treatment with a variety of therapies either alone or together.
Patients were assigned to ralinepag (n = 40; Arena Pharmaceuticals) or placebo (n = 21) for a 9-week titration period then a 13-week maintenance period. The titration period involved 10 µg of the treatment twice a day, which was increased weekly up to 300 µg twice a day as tolerated.
“Ralinepag is an oral IP receptor agonist, and it focuses on the prostacyclin pathway, which we’ve learned over the years is very important in the management of patients with pulmonary hypertension,” McLaughlin said. “These patients don’t make enough ... prostacyclin, or PGI2, and that’s an agent that in everyone’s bodies help blood vessels relax, and chronically it causes them to not proliferate and grow as much. This is one of the very clear pathobiologic problems in patients with pulmonary arterial hypertension.”
Patients underwent right heart catherization at baseline and at the end of treatment.
The primary efficacy endpoint was a change in pulmonary vascular resistance from baseline to week 22. Changes in 6-minute walk distance, safety and tolerability and hemodynamics were also assessed.
Pulmonary vascular resistance improved by a median of 163.9 dyn.s.cm-5 in patients assigned ralinepag vs. a worsening of 0.7 dyn.s.cm-5 in those assigned placebo (P = .02). The ralinepag group had a 29.8% improvement in pulmonary vascular resistance compared with the placebo group (P = .03) and a 20.1% improvement from baseline.
Changes in 6-minute walk distance was not significantly different between the two groups. Two patients died in the placebo group, and more serious adverse events occurred in the placebo group (28.6%) vs. the ralinepag group (10%).
“I’m optimistic about this particular drug,” McLaughlin told Cardiology Today. “It appears to have a very good pharmacokinetic and pharmacodynamic profile, so it may be a very potent IP receptor agonist in a once-daily dose [and] is something that is very beneficial to the patients. As a scientist, the most important thing at this point is how things look in further clinical trials that are larger.”
“These phase 2 results are extremely compelling, particularly considering the contemporary patient population of our trial in which 65% [of] patients were already receiving dual background therapies and all patients were receiving at least one therapy,” Preston Klassen, MD, MHS, executive vice president of research and development and chief medical officer of Arena Pharmaceuticals, said in a press release. – by Darlene Dobkowski
Reference:
Torres F, et al. Late-Breaking Abstracts. Presented at: American College of Chest Physicians Annual Meeting; Oct. 28-Nov. 1, 2017; Toronto.
Disclosures: McLaughlin reports she serves as a consultant and/or advisor for Actelion Pharmaceuticals, Arena Pharmaceuticals, Bayer, Gilead Sciences, Merck, Steadymed, St. Jude Medical and United Therapeutics. Klassen is an employee of Arena.