New PAH Drug, Uptravi, Moves Step Closer to Approval in Europe

Action Pharmaceuticals recently announced that the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) has released a positive opinion on the use of Uptravi (selexipag) for the treatment of patients with a diagnosis of pulmonary arterial hypertension (PAH).

Uptravi is an oral IP prostacyclin receptor agonist. The drug acts by relaxing muscles in the walls of blood vessels to dilate (open) them, decreasing the elevated pressure in the vessels supplying blood to the lungs.

The drug received CHMP’s approval  for patients with a diagnosis of PAH with the WHO functional class II-III, either as a combined treatment in those whose disease is insufficiently controlled through the use an endothelin receptor antagonist (ERA) and/or a phosphodiesterase type 5 (PDE-5) inhibitor, or as treatment alone in those patients not eligible for these treatments. The committee’s positive opinion will now be considered by the European Commission, which issues final approval.

The efficacy of Uptravi has been shown in patients with PAH, including those suffering with heritable and idiopathic PAH, PAH associated with connective tissue conditions, and PAH associated with congenital heart disease.

CHMP’s recommendation was based on Uptravi’s safety and efficacy demonstrated in GRIPHON, a long-term Phase 3 clinical trial in 1,156 PAH patients with WHO Functional Class I-IV symptoms. Patients received Uptravi combined with an ERA, a PDE-5 inhibitor, an ERA with a PDE-5 inhibitor, or treatment with Uptravi alone.

“The prostacyclin pathway is one of the fundamental pathways to be targeted in PAH. However, it has been underutilized, mainly because of the significant burden that the route of administration of existing treatments places on patients and their caregivers. This positive opinion moves us a step closer to the EMA-approval of Uptravi (selexipag), with the promise of efficacious oral treatment, supported by excellent long-term outcome results, within reach,” Dr. Marius Hoeper, a GRIPHON Steering Committee member, said in press release.

Uptravi was shown in the GRIPHON trial to be effective in reducing hospitalization for PAH, and reducing the risks of disease progression compared to placebo. Participants were treated with Uptravi for a median duration of 76.4 weeks, versus 71.2 weeks in patients treated with a placebo.

Common reported adverse effects in those who received Uptravi  treatment included diarrhea, nausea, headache, flushing, jaw pain, vomiting, muscle pain, and pain in an extremity.

Dr. Jean-Paul Clozel, chief executive officer of Actelion, said: “We are delighted by today’s announcement of a positive CHMP opinion. Coming hot on the heels of both the US and Canadian approvals, we believe that Uptravi can significantly improve long-term outcomes for PAH patients. Once market authorization is granted by the EU Commission, Uptravi will open up the prostacyclin pathway to many more patients.”

The European Commission’s final decision is expected by early April 2016.