• Selexipag significantly reduced the risk of a morbidity/mortality event by 40% versus placebo (p<0.0001)
  • Selexipag improved long-term outcomes in an investigational trial of patients already treated with ERA and PDE-5i combination therapy, with ERA or PDE-5i monotherapy and in treatment-naïve patients

 

ALLSCHWIL, SWITZERLAND – 15 March 2015 – Actelion Ltd (SIX: ATLN) today announced that key long-term outcome data from the pivotal selexipag (Uptravi®) Phase III GRIPHON study were shared during an oral presentation at the American College of Cardiology (ACC) Congress in San Diego, US. The presentation highlighted that the investigational drug selexipag significantly reduced the risk of a morbidity/mortality event by 40% versus placebo (p<0.0001) in patients with pulmonary arterial hypertension (PAH). The presentation was given by Vallerie McLaughlin M.D., Director of the Pulmonary Hypertension Program in the Division of Cardiovascular Medicine at the University of Michigan, United States and Steering Committee member of the GRIPHON study.

In this pivotal, double-blind, placebo-controlled, event-driven trial, 1,156 patients suffering from PAH were randomized 1:1 to placebo or selexipag. Patients were treated for up to 4.3 years, with median exposure to study treatment of 63.1 weeks for patients on placebo (n=582), and 70.6 weeks for patients on selexipag (n=574).

At enrolment, 80% of patients were already receiving therapy for PAH, with 15% receiving endothelin receptor antagonist (ERA) monotherapy, 32% receiving phosphodiesterase-5 inhibitor (PDE-5i) monotherapy and 33% receiving a combination of both an ERA and a PDE-5i. At baseline, 47% of patients were in WHO Functional Class I/II and 53% in Functional Class III/IV.

Dr. McLaughlin commented on the findings shared at ACC: “As the first event-driven study with a treatment targeting the prostacyclin pathway, the results presented today have been eagerly awaited. The data suggest that, should selexipag be approved, many more of our PAH patients can be treated proactively with an oral therapy targeting this pathway, offering long-term outcome benefits. In addition, a key highlight is the benefit shown in patients already receiving treatment for PAH, including those already on combination therapy at baseline.”

CONSISTENT KEY SUBGROUP FINDINGS

The reduction in risk of a morbidity/mortality event was consistent across key subgroups; age, gender, PAH etiology, baseline WHO Functional Class and irrespective of background therapy, including patients receiving selexipag on top of a combination of both an ERA and a PDE-5i.

DOSING IN GRIPHON

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 the 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.

SIX-MINUTE WALK DISTANCE

Treatment with selexipag also led to a statistically significant increase in six-minute walk distance (6MWD) at week 26 of 12 meters in the entire patient population (p=0.0027), with an improvement of 34 meters in PAH-treatment-naïve patients (p=0.0002).

SAFETY AND TOLERABILITY

Tolerability of selexipag in GRIPHON was consistent with therapies targeting the prostacyclin pathway. Adverse reactions occurring more frequently (>5%) on selexipag compared to placebo, over the course of the study, were headache, diarrhea, jaw pain, nausea, myalgia, vomiting, pain in extremity, and flushing.

Over the course of the study, the proportion of patients discontinuing treatment due to adverse events, without a morbidity or mortality event, was 14% on selexipag and 7% on placebo.

Further data from the GRIPHON study will be shared through scientific publication.

Source: http://www.actelion.com/en/our-company/news-and-events.page?newsId=1903447

ALLSCHWIL, SWITZERLAND – 03 March 2015 – Actelion Ltd (SIX: ATLN) today announced the formal acceptance of the New Drug Application (NDA) for selexipag (Uptravi®) by the US Food and Drug Administration (FDA).

The NDA dossier for selexipag (Uptravi) in the treatment of pulmonary arterial hypertension (PAH) was submitted to the FDA on the 22nd December 2014. Actelion expects results from the review process 12 months from the date of NDA submission.

The FDA application for selexipag (Uptravi), the first selective oral prostacyclin IP receptor agonist, is based on the findings of the positive pivotal Phase III GRIPHON study in 1,156 patients with pulmonary arterial hypertension (PAH).

The GRIPHON study demonstrated that selexipag decreased the risk of a morbidity/mortality event versus placebo by 40% (p<0.0001). Efficacy observed was consistent across the key subgroups: age, gender, WHO Functional Class, PAH etiology and background PAH therapy. Patients were treated for up to 4.2 years. The tolerability profile of selexipag in GRIPHON was consistent with prostacyclin therapies. Adverse reactions occurring more frequently (>5%) on selexipag compared to placebo are headache, diarrhea, jaw pain, nausea, myalgia, vomiting, pain in extremity, and flushing.

Jean-Paul Clozel, M.D. and Chief Executive Officer of Actelion commented: “The acceptance of the Uptravi dossier by the FDA is great news, our team has put considerable efforts into delivering a high quality dossier and this takes us one step closer to offering a new treatment option to the PAH community. I am looking forward to sharing our deep understanding of the data with health authorities throughout 2015 and also with the broader scientific community, starting with the first presentation at ACC in March.”

The first scientific presentation of the data will take place at the 2015 American College of Cardiology congress (ACC.15) on Sunday March 15th in San Diego, California.

Source: http://www.actelion.com/en/our-company/news-and-events.page?newsId=1899057