Actelion announces US commercial availability of UPTRAVI (selexipag) as of 4 January 2016

  • UPTRAVI® - FDA approved on 21 December 2015 for treatment of pulmonary arterial hypertension (PAH, WHO Group 1) to delay disease progression and reduce the risk of hospitalization for PAH - now available for patients in the US

SOUTH SAN FRANCISCO - 04 January 2016 - Actelion (SIX: ATLN) today announced the commercial availability of the oral, selective, IP prostacyclin receptor agonist, UPTRAVI® (selexipag) for the treatment of pulmonary arterial hypertension (PAH) in the US.

UPTRAVI is indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) to delay disease progression and reduce the risk of hospitalization for PAH.

Effectiveness was established in a long-term study in PAH patients with WHO Functional Class II-III symptoms. Patients had idiopathic and heritable PAH (58%), PAH associated with connective tissue disease (29%), PAH associated with congenital heart disease with repaired shunts (10%).

Richard Channick, MD, Director, Pulmonary Hypertension and Thromboendarterectomy Program, Massachusetts General Hospital, Boston commented: "After 20 years of prostacyclin therapy I am very excited to have UPTRAVI, an oral treatment that targets the prostacyclin pathway and is proven to improve long-term outcomes for patients. Furthermore, with UPTRAVI we can now use oral combination therapy regimens that target the three established treatment pathways for PAH, an option that could change the way we treat PAH in the long-term."

Bill Fairey, President of Actelion Pharmaceuticals US, commented: "Today's announcement represents a milestone for PAH treatment in the US - the availability of a new oral medication that effectively targets the prostacyclin pathway. We are proud to bring an oral treatment to patients which is supported by robust outcome-based evidence in combination with an ERA, or a PDE-5 inhibitor, and even in combination with both an ERA and a PDE-5 inhibitor. "

Rino Aldrighetti, President and CEO of the Pulmonary Hypertension Association spoke of the impact of the availability of UPTRAVI on the PAH community: "We at the Pulmonary Hypertension Association welcome new treatment options that help patients and their families affected by this devastating disease. We hope that UPTRAVI, will enable physicians to impact the long-term outcome for many of their PAH patients."

The safety of UPTRAVI has been evaluated in a long-term, placebo-controlled study enrolling 1,156 patients with symptomatic PAH (GRIPHON study). The exposure to UPTRAVI in this trial was up to 4.2 years with median duration of exposure of 1.4 years. Adverse reactions occurring more frequently on UPTRAVI compared to placebo - greater than or equal to 3% - over the course of the study, were headache, diarrhea, jaw pain, nausea, myalgia, vomiting, pain in extremity, flushing, arthralgia, anemia, decreased appetite and rash. These adverse reactions are more frequent during the dose titration phase. Hyperthyroidism was observed in 1% (n=8) of patients on UPTRAVI and in none of the patients on placebo.

UPTRAVI is available in the following strengths: 200 mcg [Light yellow tablet debossed with 2], 400 mcg [Red tablet debossed with 4], 600 mcg [Light violet tablet debossed with 6], 800 mcg [Green tablet debossed with 8], 1000 mcg [Orange tablet debossed with 10], 1200 mcg [Dark violet tablet debossed with 12], 1400 mcg [Dark yellow tablet debossed with 14], 1600 mcg [Brown tablet debossed with 16]. Full prescribing information can be found on www.uptravi.com.

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NOTES TO EDITOR

REGULATORY STATUS OF SELEXIPAG
In December 2014, Actelion submitted the registration dossier for selexipag to both the US FDA and Europe's EMA. Approval from the FDA was received on 21 December 2015. Review with EMA is ongoing. Submission of the registration dossier to other Health Authorities is ongoing with regulatory reviews underway in Australia, Canada, New Zealand, South Korea, Switzerland, and Taiwan.

ABOUT UPTRAVI® (SELEXIPAG) [2-6]
UPTRAVI (selexipag), originally discovered and synthesized by Nippon Shinyaku, is a potent, oral, selective IP prostacyclin receptor agonist.

UPTRAVI and its major metabolite selectively target the prostacyclin receptor (also called IP receptor). The IP receptor is one of 5 major types of prostanoid receptor (IP, EP, DP, TP, FP). Prostacyclin activates the IP receptor to induce vasodilation and inhibit proliferation of vascular smooth muscle cells.

ABOUT THE GRIPHON STUDY [1]
GRIPHON, (Prostacyclin (PGI2) Receptor agonist In Pulmonary arterial HypertensiON) was a randomized, multicenter, double-blind, placebo-controlled trial evaluating the long-term efficacy and safety of oral selexipag in patients with PAH.

The GRIPHON study was the largest randomized, controlled, outcome trial ever conducted in PAH patient population, enrolling 1,156 patients in 181 centers from 39 countries in North and Latin America, Europe, and Asia-Pacific. Patients received twice daily administration of selexipag or placebo and were also permitted to receive background PAH-specific therapy of an endothelin receptor antagonist and/or a phosphodiesterase-5 inhibitor when on a stable dose for at least 3 months. At baseline, 80% of patients were receiving oral medication specific for PAH: either an ERA, a PDE-5 inhibitor, or a combination of the two.

This pivotal, event-driven study was designed to demonstrate a prolongation in time to the first morbidity or mortality event for selexipag compared to placebo and to evaluate the safety profile of selexipag in PAH patients. All morbidity and mortality events reported by the investigators were adjudicated by a three person independent Critical Event Committee blinded to the study treatment.

ABOUT THE SAFETY AND TOLERABILITY IN GRIPHON
Overall, 41 (7.1%) patients in the placebo group and 82 (14.3%) in the selexipag group prematurely discontinued treatment due to an adverse event. The most frequent adverse events leading to treatment discontinuation in the selexipag group (>1% difference between selexipag and placebo) were headache (3.3%), diarrhea (2.3%), and nausea (1.7%). Hyperthyroidism occurred in eight selexipag-treated patients and led to treatment discontinuation in one patient. No serious adverse events were reported more frequently (>1% difference between selexipag and placebo) in the selexipag group. Prostacyclin-associated adverse events were more frequent during the titration phase, where they were used to define the individualized highest tolerated dose.

THE ROLE OF THE PROSTACYCLIN PATHWAY [7]
The prostacyclin pathway is one of the 3 best characterized pathways involved in the pathophysiology and treatment of PAH. Prostacyclin is a prostanoid and serves as a signaling molecule in the human body. It is produced, like other vasoactive substances, by endothelial cells. Prostacyclin induces vasodilation, is anti-proliferative, has anti-inflammatory effects and inhibits platelet aggregation. In certain disease conditions, the production of prostacyclin by the endothelium is impaired, allowing for example, the deleterious effects of excessive levels of endothelin or thromboxane to predominate.

PULMONARY ARTERIAL HYPERTENSION (PAH)
PAH is a chronic, life-threatening disorder characterized by abnormally high blood pressure in the arteries between the heart and lungs of an affected individual. The symptoms of PAH are non-specific and can range from mild breathlessness and fatigue during normal daily activity to symptoms of right heart failure and severe restrictions on exercise capacity and ultimately reduced life expectancy.

PAH is one group within the classification of pulmonary hypertension (PH). This group includes idiopathic PAH, heritable PAH and PAH caused by factors which include connective tissue disease, HIV infection and congenital heart disease.

The last decade has seen significant advances in the understanding of the pathophysiology of PAH, which has been paralleled with developments of treatment guidelines and new therapies. Drugs targeting the three pathways that have been established in the pathogenesis of PAH are endothelin receptor antagonists (ERAs), prostacyclin analogs and phosphodiesterase-5 inhibitors. PAH treatments have transformed the prognosis for PAH patients from symptomatic improvements in exercise tolerance 10 years ago to delayed disease progression today. Improved disease awareness and evidence-based guidelines developed from randomized controlled clinical trial data have highlighted the need for early intervention, goal-oriented treatment and combination therapy.

ABOUT THE ACTELION / NIPPON SHINYAKU ALLIANCE
Actelion and Nippon Shinyaku entered into an exclusive worldwide alliance in April 2008 to collaborate on selexipag, a first orally-available, selective prostacyclin IP receptor agonist for patients suffering from PAH. This compound was originally discovered and synthesized by Nippon Shinyaku. Actelion is responsible for global development and commercialization of selexipag outside Japan, while the two companies will co-develop and co-commercialize in Japan. Nippon Shinyaku will receive milestone payments based on development stage and sales milestones as well as royalties on any sales of selexipag.

ABOUT RICHARD CHANNICK
Richard Channick, MD, is Director of the Pulmonary Hypertension and Thrombo-endarterectomy Program at Massachusetts General Hospital and Associate Professor of Medicine at Harvard Medical School. Dr. Channick received his medical degree at Temple University Medical School, where he was elected to the Alpha Omega Alpha Medical Honor Society. He did his residency and was Chief Resident at University of Massachusetts Medical Center. He did a Pulmonary and Critical Care Fellowship at University of California, San Diego Medical Center. Dr. Channick has published over 100 original articles, chapters and reviews focused on all aspects of pulmonary hypertension. He serves on many national and international leadership committees including the American Thoracic Society Pulmonary Circulation Program Committee and the ACCP Pulmonary Vascular Disease Network Steering Committee. He is currently Chair of the Scientific Leadership Committee for the Pulmonary Hypertension Association. Dr. Channick has served on the steering committees for several pivotal clinical trials in pulmonary hypertension and lectures nationally and internationally. Dr. Channick is a member of the GRIPHON Steering Committee and has been a consultant for Actelion, the sponsor of the study and manufacturer of UPTRAVI.

 

References

  1. Sitbon O et al. Selexipag for the Treatment of Pulmonary Arterial Hypertension. N Engl J Med 2015; 373:2522-33.
  2. Kuwano et al. A long-acting and highly selective prostacyclin receptor agonist prodrug, NS-304, ameliorates rat pulmonary hypertension with unique relaxant responses of its active form MRE-269 on rat pulmonary artery. J Pharmacol Exp Ther 2008;326:691-699.
  3. Kuwano K et al. 2-[4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy]-N-(methylsulfonyl)acetamide (NS-304), an orally available and long-acting prostacyclin receptor agonist prodrug. J Pharmacol Exp Ther 2007;322(3):1181-1188.
  4. Tetsuo Asaki et al. Selexipag: an oral and selective IP prostacyclin receptor agonist for the treatment of pulmonary arterial hypertension. J. Med. Chem., Just Accepted Manuscript. DOI: 10.1021/acs.jmedchem.5b00698. Web: 20 Aug 2015.
  5. Morrison et al. Selexipag: a selective prostacyclin receptor agonist that does not affect rat gastric function. J Pharmacol Exp Ther 2010;335:249-255.
  6. Morrison et al. Differential effects of selexipag and prostacyclin analogs in rat pulmonary artery. J Pharmacol Exp Ther 2012;343:547-555.
  7. Simonneau G, Lang I, Torbicki A, Hoeper MM, Delcroix M, Karlocai K, Galie N. Selexipag, an oral, selective IP receptor agonist for the treatment of pulmonary arterial hypertension Eur Respir J 2012; 40: 874-880.
  8. Mubarak KK. A review of prostaglandin analogs in the management of patients with pulmonary arterial hypertension. Respir Med 2010;104:9-21.

INVESTOR CONFERENCE CALL / WEBCAST

An investor conference call & webcast will be held to discuss US FDA approval of Uptravi (selexipag) for the treatment of pulmonary arterial hypertension at 14:00hrs on 05 January 2016.

Date/Time:

     
05 January 2016 14:00hrs - 15:00hrs Basel (CET)
  13:00hrs - 14:00hrs UK (GMT)
  8:00 a.m. - 9:00 a.m. US (EST)

   

Conference Call Connect #:

Dial-in participants should start calling the number below 10-15 minutes before the conference is due to start.

       
Dial: Europe: +41 (0)44 583 18 01
  UK: +44 203 194 0561
  US: +1 646 722 4897
           

Participant's mode:

Listen-Only with possibility to open individual lines during Q&A session.
Participants will be asked for their Name and Company.

Webcast Access:

Webcast participants should visit the Actelion website www.actelion.com 10-15 minutes before the conference is due to start.

NIPPON SHINYAKU
For further information on Nippon Shinyaku please visit:
http://www.nippon-shinyaku.co.jp/english/index.html

ACTELION LTD
Actelion Ltd. is a leading biopharmaceutical company focused on the discovery, development and commercialization of innovative drugs for diseases with significant unmet medical needs.
Actelion is a leader in the field of pulmonary arterial hypertension (PAH). Our portfolio of PAH treatments covers the spectrum of disease, from WHO Functional Class (FC) II through to FC IV, with oral, inhaled and intravenous medications. Although not available in all countries, Actelion has treatments approved by health authorities for a number of specialist diseases including Type 1 Gaucher disease, Niemann-Pick type C disease, Digital Ulcers in patients suffering from systemic sclerosis, and mycosis fungoides type cutaneous T-cell lymphoma.
Founded in late 1997, with now over 2,400 dedicated professionals covering all key markets around the world including Europe, the US, Japan, China, Russia and Mexico, Actelion has its corporate headquarters in Allschwil / Basel, Switzerland.
Actelion shares are traded on the SIX Swiss Exchange (ticker symbol: ATLN) as part of the Swiss blue-chip index SMI (Swiss Market Index SMI®). All trademarks are legally protected. 

For further information please contact:

Andrew C. Weiss
Senior Vice President, Head of Investor Relations & Corporate Communications
Actelion Pharmaceuticals Ltd, Gewerbestrasse 16, CH-4123 Allschwil
+41 61 565 62 62
http://www.actelion.com

The above information contains certain "forward-looking statements", relating to the company's business, which can be identified by the use of forward-looking terminology such as "estimates", "believes", "expects", "may", "are expected to", "will", "will continue", "should", "would be", "seeks", "pending" or "anticipates" or similar expressions, or by discussions of strategy, plans or intentions. Such statements include descriptions of the company's investment and research and development programs and anticipated expenditures in connection therewith, descriptions of new products expected to be introduced by the company and anticipated customer demand for such products and products in the company's existing portfolio. Such statements reflect the current views of the company with respect to future events and are subject to certain risks, uncertainties and assumptions. Many factors could cause the actual results, performance or achievements of the company to be materially different from any future results, performances or achievements that may be expressed or implied by such forward-looking statements. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those described herein as anticipated, believed, estimated or expected

CORPORATE EVENTS

21 July 2016 HY Results 2016 
20 October 2016 Q3 Results 2016 
14 February 2017  FY Results 2016 
20 April 2017 Q1 Results 2017
21 July 2016 HY Results 2016 
20 October 2016 Q3 Results 2016 
14 February 2017  FY Results 2016 
20 April 2017 Q1 Results 2017