Arena Pharmaceuticals has announced positive results for ralinepag (APD811), an investigational prostacyclin receptor agonist being investigated in a Phase 2 trial to treat pulmonary arterial hypertension (PAH).
Ralinepag is an oral drug that targets the prostacyclin pathway. The drug was developed for the treatment of PAH, due to its action on vasodilation and its ability to prevent both the proliferation of vascular smooth muscle cells as well as platelet aggregation.
Ralinepag showed successful primary efficacy results, with significant improvement in pulmonary vascular resistance and safety data that is consistent with similar drugs, said San Diego-based Arena.
The Phase 2 randomized, double-blind, placebo-controlled, dose-ranging trial (NCT02279160) included 61 adults with PAH. Primary effectiveness analyses at week 22 of treatment showed a statistically significant absolute change from baseline regarding pulmonary vascular resistance (20.1 percent improvement), and compared to placebo (29.8 percent improvement), and an improvement in the 6-minute walk distance (6MWD; a test accessing exercise capacity).
Adverse events observed during the trial were consistent with other prostacyclin treatments used to manage PAH, namely nausea, jaw pain, headache, diarrhea and flushing.
“The results of this Phase 2 study of ralinepag, in patients already receiving, in most cases, multiple background therapies, showed a clinically meaningful improvement in PVR [pulmonary vascular resistance], a well-established indicator of treatment benefit believed to be correlated with long-term clinical outcomes in patients with PAH,” Dr. Vallerie McLaughlin, director of the University of Michigan’s pulmonary hypertension program, said in a press release.
Patients who completed week 22 of the trial were eligible to transition to an open-label extension study (NCT02279745) assessing the long-term safety and tolerability of ralinepag.
“The positive outcome of this Phase 2 trial in a contemporary PAH patient population is an important milestone in the development of ralinepag for the treatment of patients suffering from this grievous illness,” said Dr. Preston Klassen, Arena’s chief medical officer and executive vice president of R&D. “It is exciting to see the positive nonclinical pharmacological profile translating into potentially the first oral prostacyclin therapy that may approach consistent therapeutic levels without the complexity of parenteral (IV) therapy. These data give us confidence to move expeditiously toward a Phase 3 clinical program.”
Ralinepag is currently an investigational compound. No country has yet approved its use.