• 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.

 

Source: http://www.actelion.com/en/our-company/news-and-events.page?newsId=1982198

ALLSCHWIL/BASEL, SWITZERLAND – 11 January 2016 - Actelion Ltd (SIX: ATLN) announced today that representatives from Actelion will present at upcoming investor conferences.

  • Jean-Paul Clozel, Chief Executive Officer of Actelion, will present at the 34th J. P. Morgan Healthcare Conference on 12 January 2016 at 08:00 AM Pacific Standard Time / 17:00 hrs. Central European Time (CET) at the Westin St. Francis Hotel in San Francisco, US.
  • Otto Schwarz, Chief Operating Officer of Actelion, will present at the Helvea Swiss Equities Conference on 14 January 2016.
  • Jean-Paul Clozel will then present again at the Bank am Bellevue “Bellevue Meets Management Seminar” on 15 January 2016.

At J. P. Morgan, Jean-Paul Clozel will describe the progress made during 2015, the ongoing transformation of Actelion’s PAH franchise, how the company is transforming beyond PAH, and what’s ahead in 2016.

Jean-Paul Clozel commented: “With the impressive take-off of Opsumit® (macitentan) and now Uptravi® (selexipag) on the market, we have a great platform to invest in our future. I am looking forward to presenting the progress we have made in 2015. The transformation of our PAH franchise is fueling our pipeline outside PAH, with several promising compounds advancing in the clinic. The transformation of Actelion is now well underway.”

The company will confirm that the strong operating performance, driven by the unabated launch trajectory of Opsumit, is expected to lead to core earnings growth that crosses the 20% mark at constant exchange rates and excluding prior-year US rebate reversals.

Jean-Paul Clozel continued: “2015 was yet another exciting year for Actelion and I am confident that there is much more excitement ahead as we transform Actelion, which I hope to give a flavor of in my presentation. We have the products, we have the ideas, we have a fully integrated infrastructure and, very importantly, we have the money to finance this transformation without compromising our profitability.”
At Helvea Swiss Equities Conference, Otto Schwarz will provide an overview of the business dynamics for Actelion’s products, in particular in relation to the transformation of the PAH portfolio.

Otto Schwarz commented: “Our PAH franchise has evolved from a single product into a portfolio of unique and complementary products, which cover the continuity of care in this severe disease. The dynamics of this transformation is reflected in the performance of our products in the market. Opsumit has had a highly successful launch and we are confident to continue this momentum into 2016. As a result of the success of Opsumit, we have seen a decline in Tracleer sales, which is expected to accelerate as generic competition becomes available in the US.”

Otto Schwarz concluded: “Of course, all eyes will be on the launch of Uptravi, which is now available to patients in the US. Feedback from prescribers has been very positive and they are very excited to add this first outcome-based oral prostacyclin product to their treatment options.”

CLINICAL UPDATE
Actelion’s promising R&D pipeline comprises novel compounds addressing a broad range of diseases, including cardiovascular and immunological disorders as well as central nervous system disorders and infectious diseases.

Actelion’s late-stage product candidates include the novel antibiotic cadazolid, under investigation for Clostridium difficile-associated diarrhea (CDAD) and a S1P1 receptor modulator, ponesimod, investigated in multiple sclerosis.

At the end of 2015, the initial results of the Phase II MELODY study with macitentan became available. MELODY was a prospective, multicenter, double-blind, randomized, placebo-controlled, parallel-group, 12-week study to evaluate the safety and tolerability of macitentan in subjects with combined pre- and post-capillary pulmonary hypertension (CpcPH) due to left ventricular dysfunction. In the exploratory Phase II study, macitentan was generally well tolerated in this Group 2 pulmonary hypertension patient population with heart failure. In addition, encouraging hemodynamic effects were observed. The company will now fully evaluate the data and, together with the results of the current Phase II study with a new endothelin receptor antagonist (ERA), make a decision on the future development strategy of Actelion’s ERAs beyond PAH.

Despite encouraging preclinical data, results from the Phase I/Ib open-label studies in patients with recurring glioblastoma and newly diagnosed glioblastoma disappointingly do not support further investigation in this indication. Dose escalation had reached 300 mg per day, without any significant tolerability issues, before the decision was made to stop the investigation.

At the end of 2015, a New Chemical Entity entered Phase I clinical development for cardiovascular disorders.

DEVELOPMENT PIPELINE

Phase Compound Indication Study Status
Registration Selexipag PAH GRIPHON Regulatory reviews ongoing
III Cadazolid Clostridium difficile-associated diarrhea IMPACT Ongoing
III Macitentan Eisenmenger syndrome MAESTRO Ongoing
III Ponesimod Multiple sclerosis OPTIMUM Ongoing
II Clazosentan Reversal of vasospasm associated with aneurysmal subarachnoid hemorrhage - Initiating
II Endothelin Receptor Antagonist Specialty cardiovascular disorders - Initiating
II Macitentan Chronic thromboembolic pulmonary hypertension MERIT Ongoing
II Macitentan Combined pre- and post-capillary pulmonary hypertension MELODY Complete
II Ponesimod Graft-versus-host disease - Ongoing
II S1P1 modulator Systemic lupus erythematosus - Ongoing
Ib Lucerastat Fabry disease - Ongoing
I NCE Neurological disorders - Ongoing
I NCE Neurological disorders - Ongoing
I NCE Cardiovascular disorders - Ongoing

Pipeline status as of 31 December 2015

Source: http://www.actelion.com/en/our-company/news-and-events.page?newsId=1977810

ALLSCHWIL, SWITZERLAND – 23 December 2015 – Actelion (SIX: ATLN) announced today that the New England Journal of Medicine (NEJM) has published the results of the oral, selective IP prostacyclin receptor agonist, selexipag, in patients with pulmonary arterial hypertension (PAH).

Olivier Sitbon, MD, and primary author of the NEJM paper commented: “Selexipag has the potential to improve PAH management, and the publication by the New England Journal of Medicine reflects the importance of our findings in the GRIPHON study. For the first time we see an effect on long-term outcome with an oral therapy that targets the prostacyclin pathway, a pathway that has for too long been underutilized in the treatment of PAH patients.”

The NEJM paper presents the results of the GRIPHON study, a multicenter, Phase III study in which 1,156 patients, 79.6% of whom were already treated for PAH at baseline, received either placebo or selexipag for a median of 63.7 weeks and 70.7 weeks respectively. The patients’ dose was adjusted weekly until the individualized maximum tolerated dose was achieved (ranging from 200 micrograms twice daily to 1,600 micrograms twice daily).

In GRIPHON, the risk of the primary composite endpoint of death from any cause or complication related to PAH up to the end of the treatment period was reduced by 40% (p<0.001) with selexipag compared to placebo. The treatment effect was driven by hospitalization and disease progression, which accounted for 81.9% of the primary endpoint events. The benefit of selexipag was consistent across pre-specified patient sub-groups such as PAH classification, WHO functional class and use of medication for PAH, which included patients receiving an ERA and a PDE-5 inhibitor at baseline (n = 376; 32.5%).

Gérald Simonneau, MD, and a senior author of the NEJM paper commented: “These data show that significant improvements in long-term outcomes can be achieved in a broad range of PAH patients by targeting the prostacyclin pathway with selexipag. Even better, the improvement is seen in patients already receiving combination therapy with an ERA and PDE-5 inhibitor, opening the door to triple oral combination therapy in PAH.”

Vallerie McLaughlin, MD, and a senior author of the NEJM paper commented: “The long-term benefits we have seen in the GRIPHON study suggest that we now have effective oral therapies utilizing all three key PAH pathways, a development that could enhance PAH care for many patients.”

The adverse events observed with selexipag were consistent with those typically observed for prostacyclin therapies, including headache, diarrhea, nausea, and jaw pain. These adverse events were typically mild to moderate in severity. Overall, 7.1% of placebo-treated patients and 14.3% of selexipag-treated patients prematurely discontinued treatment due to adverse events.

Jean-Paul Clozel, MD and Chief Executive Officer of Actelion commented: “I am very proud that Actelion has – for the second time – a new drug effective in a long-term outcome study in PAH, published in the New England Journal of Medicine. Selexipag was recently approved by the US FDA for the treatment of PAH to delay disease progression and reduce the risk of hospitalization for PAH, and is under review by other regulatory authorities around the world. Together with our partners at Nippon Shinyaku, we hope to see the very significant benefit of treatment with selexipag made available to the PAH community very soon. I would like to take this occasion to thank the patients and investigators who contributed to this ground-breaking study.”

Source: http://www.actelion.com/en/our-company/news-and-events.page?newsId=1975767

 

  • Uptravi® approved for treatment of pulmonary arterial hypertension (PAH, WHO Group 1) to delay disease progression and reduce the risk of hospitalization for PAH
  • Uptravi will be made available to patients in the US in early January 2016
  • Uptravi will become a significant treatment option in PAH and complements Actelion’s portfolio with Opsumit® and Veletri®

ALLSCHWIL, SWITZERLAND – 22 December 2015 – Actelion (SIX: ATLN) announced today that the United States Food and Drug Administration (FDA) has approved 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 (PAH).

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%).

Vallerie McLaughlin MD, Director of the Pulmonary Hypertension Program in the Division of Cardiovascular Medicine at the University of Michigan, United States, commented: “The prostacyclin pathway has long been recognized as a key target in PAH treatment. However, until now, it has been underutilized. This is in part due to the significant burden existing prostanoid treatments have placed on the patients and on those supporting them. The approval of Uptravi with its convincing long-term outcome results means that many more patients can benefit from this pathway and be treated much earlier in the course of their disease.”

Jean-Paul Clozel, MD and Chief Executive Officer of Actelion, commented: “Today’s FDA approval of Uptravi is another major landmark for Actelion. Together with our partners at Nippon Shinyaku we are proud to be able to offer an outstanding oral therapy targeting the prostacyclin pathway. The label for Uptravi recognizes the improvement in long-term outcomes, including reducing the risk of hospitalization for PAH regardless of whether patients received background therapy including an ERA, a PDE-5 inhibitor, or – for the first time ever in PAH – on top of a combination of both, an ERA and a PDE-5 inhibitor.”

Jean-Paul Clozel concluded: “Uptravi will significantly expand the options to delay disease progression after initiation of therapy with a baseline treatment like Opsumit and well ahead of Veletri for the late disease stage. Actelion now has an unparalleled portfolio of treatments across the continuum of care in PAH that offer a combination of long term-efficacy, safety and convenience.”

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.

Actelion expects Uptravi to become available to patients in the United States in early January 2016. Outside of the United States, Actelion continues to work with health authorities to obtain regulatory approval for Uptravi.

ABOUT THE GRIPHON STUDY DATA

The Uptravi approval was based in part on data from the long-term, global, Phase III GRIPHON 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 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.

Source: http://www.actelion.com/en/our-company/news-and-events.page?newsId=1975263

ALLSCHWIL, SWITZERLAND – 23 September 2015 – Actelion Ltd (SIX: ATLN) today announced that key data from the pivotal Phase III GRIPHON study with the investigational drug selexipag (Uptravi®) will be shared through an oral presentation at the European Respiratory Society (ERS) Congress in Amsterdam, Netherlands.

The oral presentation, titled ‘Effect of selexipag on long-term outcomes in key subgroups of patients with pulmonary arterial hypertension (PAH): GRIPHON study results’* will be given by Professor Olivier Sitbon from the Hospital Le Kremlin Bicêtre, Paris, France, at 11.15 on 30 September. The abstract can be found in the congress program online.

The ERS Congress will also see the presentation of further information on macitentan (Opsumit®), with a poster titled ‘Pharmacokinetics and safety of concomitant macitentan and hormonal contraceptives’**. The poster will be presented in a poster discussion session by Dr Noémie Hurst from 10.45 on 28 September. The abstract can be found in the congress program online.
*Effect of selexipag on long-term outcomes in key subgroups of patients with pulmonary arterial hypertension (PAH): GRIPHON study results, O. Sitbon, R. Channick, K. Chin, A. Frey, N. Galiè, H.-A. Ghofrani, M.M. Hoeper, I. Lang, F.-O. Le Brun, V. McLaughlin, R. Preiss, L.J. Rubin, G. Simonneau, V. Tapson, S. Gaine
**Poster presentation: Pharmacokinetics and safety of concomitant macitentan and hormonal contraceptives, N. Hurst. M. Pellek, P.N. Sidharta, J. Dingemanse

Source: http://www.actelion.com/en/our-company/news-and-events.page?newsId=1953700