Extended Release Formulation of PAH Therapy Ralinepag Shows Promise in Phase 1 Trial

Alice Melão, MSc avatar

by Alice Melão, MSc |

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Results of a Phase 1 clinical study in healthy volunteers evaluating different formulations of Arena Pharmaceuticals’ prostacyclin receptor agonist, ralinepag, for the treatment of pulmonary arterial hypertension (PAH), showed the drug’s extended release (XR) formulation can achieve a similar body distribution profile as its immediate release (IR) capsule formulations, but with fewer intakes.

Ralinepag (APD811) is an orally administrated investigational drug candidate discovered and developed by Arena. Preclinical and clinical studies have demonstrated that ralinepag can promote the dilation of blood vessels while inhibiting the proliferation of vascular smooth muscle cells and platelet aggregation. Combined with a stable formulation and an extended half-life, these therapeutic effects can be very beneficial for the treatment of PAH.

Recently completed, the Phase 1 study compared the safety, tolerability, and distribution profiles of ralinepag XR tablets administrated once daily with ralinepag IR capsules administrated twice daily.

The IR forumulation is currently under clinical development and is expected to promote continuous exposure, while the XR formulation may improve the drug’s distribution in the body with less drug intakes.

The company expects that oral ralinepag XR tablets can achieve a similar body distribution profile as that reported for current prostacyclin therapies administrated intravenously, such as Remodulin (treprostinil) and Flolan and Veletri (epoprostenol).

Twelve healthy volunteers were included in the study and received single daily doses of ralinepag XR. Three different doses were tested. Participants also received single doses of the IR formulation.

Overall, the XR once-daily tablet regimen was shown to reduce maximum plasma concentration of the prostacyclin receptor agonist compared to the IR formulation administrated twice daily. Both ralinepag formulations and regimens maintained similar total plasma concentrations of the drug.

These results suggest that ralinepag XR can potentially promote the same therapeutic effects with the same effectiveness as its IR formulation.

Ralinepag XR’s most common treatment-related adverse events were similar to those observed previously for ralinepag IR in healthy individuals.

“We believe the results from this trial support the delivery of ralinepag as a single daily oral dose for patients with pulmonary arterial hypertension,” Preston Klassen, executive vice president of research and development and chief medical officer of Arena, said in a press release.

“We will evaluate these data further in the context of the Phase 2 data with ralinepag IR that are expected in July,” Klassen added.

Currently, ralinepag IR is being evaluated in two placebo-controlled Phase 2 clinical trials (NCT02279160 and NCT02279745). These studies are evaluating the effectiveness of ralinepag IR in treating pulmonary vascular resistance and improving the exercise capacity of PAH patients after short and long-term ralinepag treatment.