FDA Asked to Approve Intravenous Uptravi as Option When Tablets Won’t Do
Janssen Pharmaceutical has asked the U.S. Food and Drug Administration (FDA) to approve the use of intravenous Uptravi (selexipag) by pulmonary arterial hypertension (PAH) patients unable for a given time to use Uptravi as a prescribed oral treatment.
The intravenous, or IV (into-the-vein), formulation is meant to prevent treatment interruptions in adults with World Health Organization (WHO) functional class II and III — meaning patients with slight (class II) or marked (class III) limitations of physical activity.
Because of the progressive nature of PAH, interruptions in treatment present a difficult challenge and are best avoided.
“Even relatively short-term PAH treatment interruptions due to a temporary inability to take oral medication, like during surgery, can have a significant negative impact on a person’s health,” Neil Davie, PhD, global therapeutic area head for pulmonary hypertension at Janssen Research & Development, said in a press release.
The request, filed in the form of a New Drug Application, is based on results of a recent Phase 3 trial (NCT03187678) in PAH patients. It tested the safety and tolerability of temporarily changing from oral Uptravi (tablets) to an intravenous formulation, and then switching back to the initial oral dose.
In the study, 20 patients with stable PAH switched between oral and IV treatments in three defined periods.
During period one, patients received their normal oral dose in the morning and evening of the first day. Period two ran from days two to three, during which patients were given three infusions of Uptravi IV (morning and evening of day two, and morning of day three), at doses corresponding to their oral regimen. Period three began in the evening of day three, at which patients resumed their oral medication for a further nine days, followed by a longer safety follow-up period.
All 20 patients completed the study and tolerated well the change in treatment, with no unexpected safety concerns. Side effects for the IV treatment were similar to those for tablets, including nausea, headaches, and vomiting. The only IV-specific complaint was a reaction at the infusion site.
“We have demonstrated that continued treatment with Uptravi can significantly improve patients’ long-term outcomes. Preventing an interruption of treatment with an IV formulation is an important therapeutic option and we are pleased to be one step closer to bringing this important treatment to the PAH community,” Davie said.
Uptravi delays disease progression and reduces the risk of hospitalization by dilating blood vessels, thereby improving circulation and lowering blood pressure. It does this by binding to the prostacyclin receptor; prostacyclin is a hormone found on the surface of cells in blood vessels that regulates blood pressure. Low levels of prostacyclin can lead to PAH.