- The European Commission is expected to make a final decision within 67 days.
ALLSCHWIL, SWITZERLAND – 29 January 2016 – Actelion (SIX: ATLN) announced today that the Committee for Medicinal Products for Human Use (CHMP), the scientific committee of the European Medicines Agency (EMA), issued a positive opinion for the use of the orally active, selective IP prostacyclin receptor agonist Uptravi (selexipag), originally discovered and synthesized by Nippon Shinyaku, for the treatment of pulmonary arterial hypertension.
The CHMP recommended that the European Commission approves Uptravi for the long-term treatment of pulmonary arterial hypertension (PAH) in adult patients with WHO functional class (FC) II-III, either as combination therapy in patients insufficiently controlled with an endothelin receptor antagonist (ERA) and/or a phosphodiesterase type 5 (PDE-5) inhibitor, or as monotherapy in patients who are not candidates for these therapies. Efficacy has been shown in a PAH population including idiopathic and heritable PAH, PAH associated with connective tissue disorders, and PAH associated with corrected simple congenital heart disease.
The CHMP’s positive opinion is in part based on the review of efficacy and safety data generated in GRIPHON, a long-term Phase III study in PAH patients with WHO Functional Class I-IV symptoms. Patients were treated with Uptravi in combination with an ERA, a PDE-5 inhibitor, an ERA together with a PDE-5 inhibitor or as monotherapy. Patients had idiopathic and heritable PAH (58%), PAH associated with connective tissue disease (29%) or PAH associated with congenital heart disease with repaired shunts (10%).
Marius Hoeper, a GRIPHON Steering Committee member, commented: “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.”
The safety of selexipag has been evaluated in a long-term, Phase III placebo controlled study enrolling 1,156 patients with symptomatic PAH. The mean treatment duration was 76.4 weeks (median 70.7 weeks) for patients receiving selexipag versus 71.2 weeks (median 63.7 weeks) for patients on placebo. The exposure to selexipag was up to 4.2 years.
The most commonly reported adverse reactions related to the pharmacological effects of Uptravi are headache, diarrhoea, nausea and vomiting, jaw pain, myalgia, pain in extremity, arthralgia, and flushing. These reactions are more frequent during the up-titration phase. The majority of these reactions are of mild to moderate intensity.
Jean-Paul Clozel, MD and Chief Executive Officer of Actelion, commented: “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.”
A CHMP positive opinion is one of the final steps before marketing authorization is granted by the European Commission. The European Commission is expected to issue a final decision by early April 2016.
ABOUT THE GRIPHON STUDY DATA
GRIPHON was a long-term, global Phase III study in 1,156 patients treated for up to 4.2 years. The GRIPHON study, in which more than 80% of patients were already receiving PAH-specific therapies, showed that the risk of the primary composite endpoint was reduced by 40% (p<0.0001) with selexipag compared to placebo.
The benefit of selexipag was consistent across pre-specified patient subgroups such as disease etiology, functional class and baseline PAH therapy, including patients already receiving combination therapy with an ERA and a PDE-5 inhibitor.
Titrating selexipag to an individualized maintenance dose based on tolerability was effective in achieving long-term outcome benefits across the tested dose range. The dosing in GRIPHON was initiated at 200 micrograms (mcg) twice daily (b.i.d) and increased weekly in steps of 200 mcg up to a maximum of 1600 mcg b.i.d. After titrating to each patient’s individual highest tolerated dose, the benefit was consistent across the pre-specified low (200, 400 mcg b.i.d), medium (600, 800, 1’000 mcg b.i.d) and high maintenance (1’200, 1’400, 1’600 mcg b.i.d) dose groups.