New Post-hoc Analysis Shows Adding UPTRAVI®▼ (selexipag) Versus Placebo Improved Long-term Clinical Outcomes Regardless of Time of Treatment Initiation, and Demonstrated an Even More Pronounced Treatment Effect When Initiated Early

- ALLSCHWIL, Switzerland, May 20, 2019 /PRNewswire/ -- Actelion Pharmaceuticals Ltd, one of the Janssen Pharmaceutical Companies of Johnson & Johnson, has presented results of a post-hoc exploratory analysis of the GRIPHON study in patients with pulmonary arterial hypertension (PAH) showing that treatment with selexipag versus placebo improved clinical outcomes regardless of the time from diagnosis to selexipag initiation, and that the treatment effect was more pronounced in those receiving selexipag soon after diagnosis.1 The data were presented at the annual American Thoracic Society International Conference in Dallas, Texas. "This new analysis reinforces the overall efficacy data for selexipag and provides compelling evidence of the benefits of initiating selexipag early," said Prof. Sean Gaine*, MD, Consultant Respiratory Physician and Director of National Pulmonary Hypertension Unit, Mater Misericordiae University Hospital, Dublin, Ireland. "These data add to the growing evidence supporting early intensification of treatment, which is important when you consider that around a third of PAH patients currently die within five years of diagnosis.2,3 Early recognition and prompt treatment of the disease are key to achieving sustained long-term benefits." The GRIPHON study evaluated the long-term efficacy and safety of oral selexipag in 1,156 patients with PAH across 181 centers from 39 countries.4 It is the largest randomized, controlled, outcome trial ever conducted in patients with PAH, and demonstrated a 40% reduction in the primary composite endpoint of morbidity/mortality, defined as disease progression, worsening of PAH resulting in hospitalization, initiation of intravenous [IV] prostanoid therapy or long-term oxygen therapy, or the need for lung transplantation or balloon atrial septostomy, or death from any cause.4 Overall, the most common adverse events for patients receiving selexipag were headache, diarrhea, nausea, and jaw pain.4 This post-hoc analysis evaluated the impact of time from diagnosis to initiation of selexipag on the treatment response with respect to the primary endpoint of the study. Patients were categorized at baseline based on their time from diagnosis using a six-month threshold. Patients treated earlier were defined as those who received treatment ≤6 months from diagnosis (N=404), and those who were treated later received treatment >6 months from diagnosis (N=752). Selexipag reduced the risk of morbidity/mortality, compared with placebo, in both groups with a risk reduction of 55% for those treated earlier (HR, 0.45 [95% CI: 0.33–0.63]) and a risk reduction of 30% for those treated later (HR, 0.70 [95% CI: 0.54–0.91]). The response was more pronounced in those treated earlier (interaction p-value, 0.0391). This pattern was observed in all background PAH therapy subgroups. The results of the analysis are consistent with other studies and clinical guidelines that support the early initiation of treatment for PAH. "This post-hoc analysis of the GRIPHON study adds to the growing body of research which indicates that selexipag can have a significant impact on a patients' morbidity and disease progression, irrespective of background therapy," said Alessandro Maresta, MD, VP and Head of Medical Affairs at Actelion Pharmaceuticals Ltd. "At Actelion, we have helped impact the lives of more than 300,000 patients with PAH globally over the past 20 years. Today, it is essential that current treatments are used to their fullest potential so that we slow disease progression and significantly improve outcomes." Selexipag is an oral selective prostacyclin IP receptor agonist and is available for the treatment of PAH in more than 40 countries. In the US, selexipag is indicated for the treatment of PAH to delay disease progression and reduce the risk of hospitalization.5 In Europe, selexipag is indicated for the long-term treatment of 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.6 *Dr. Gaine has received research support from Actelion and has served as a paid consultant to the company. Notes to the Editor ABOUT PULMONARY ARTERIAL HYPERTENSION (PAH) PAH is a specific form of PH that causes the walls of the pulmonary arteries (blood vessels leading from the right side of the heart to the lungs) to become thick and stiff, narrowing the space for blood to flow, and causing an increased blood pressure to develop within the lungs. PAH is a serious, progressive disease with a variety of etiologies, and has a major impact on patients' functioning, as well as their physical, psychological and social wellbeing. There is currently no cure for PH and it is often fatal.2,7,8 However, the last decade has seen significant advances in the understanding of the pathophysiology of PAH, transforming the prognosis for PAH patients from symptomatic improvements in exercise tolerance 10 years ago, to delayed disease progression today. ABOUT UPTRAVI® (selexipag) UPTRAVI is an oral selective prostacyclin IP receptor agonist for the treatment of PAH. UPTRAVI is the only globally-available oral treatment that works on the prostacyclin pathway with evidence of long-term outcomes. UPTRAVI is available for the treatment of PAH in more than 40 countries. In the US, UPTRAVI is indicated for the treatment of PAH to delay disease progression and reduce the risk of hospitalization. 5 In Europe, UPTRAVI is indicated for the long-term treatment of 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.6 The efficacy of selexipag in PAH was established in GRIPHON (Prostacyclin [PGI2] Receptor agonist In Pulmonary arterial HypertensiON), the largest randomized controlled trial ever conducted in PAH patients. This double-blind, multicenter study aimed to evaluate the long-term efficacy and safety of oral selexipag and included almost 400 patients who were already receiving double combination PAH treatment. The study provided the first randomized, controlled evidence for triple oral combination therapy in PAH. Selexipag was shown to delay disease progression and significantly reduce the risk of hospitalization compared with placebo, as well as improving exercise capacity.4 Overall, the most common adverse events in the selexipag group were consistent with the known side effects of prostacyclin, including headache, diarrhea, nausea, and jaw pain.4 For complete European Union (EU) Prescribing and safety information, please visit: https://www.medicines.org.uk/emc/product/2163 ▼Adverse events should be reported. This product is subject to additional monitoring and it is therefore important to report any suspected adverse events related to this medicinal product. Reporting forms and information can be found at www.mhra.gov/yellowcard (HCPs in the UK) or www.hpra.ie (HCPs in Ireland). Adverse events should also be reported to Actelion Pharmaceuticals UK Ltd on +44 (0)208 987 3333 or at [email protected]. ABOUT ACTELION In June 2017, Actelion became part of the Janssen Pharmaceutical Companies of Johnson & Johnson. Actelion's medicines have helped to expand and strengthen Janssen's portfolio with leading, differentiated in-market medicines and promising late-stage compounds. Janssen has added Pulmonary Hypertension as a therapeutic area of focus to maintain the leadership position Actelion has built in this important disease area. Learn more at www.actelion.com. Follow us on Twitter @actelion_com. About the Janssen Pharmaceutical Companies of Johnson & Johnson At Janssen, we're creating a future where disease is a thing of the past. We're the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular & Metabolism, Immunology, Infectious Diseases & Vaccines, Neuroscience, Oncology and Pulmonary Hypertension. Learn more at www.janssen.com. Follow us at www.twitter.com/JanssenGlobal. Actelion Pharmaceuticals Ltd is one of the Janssen Pharmaceutical Companies of Johnson & Johnson. Cautions Concerning Forward-looking Statements This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding UPTRAVI® (selexipag). The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Actelion Pharmaceuticals Ltd, any of the other Janssen Pharmaceutical Companies and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended December 30, 2018, including in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors", and in the company's most recently filed Quarterly Report on Form 10-Q, and the company's subsequent filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. None of the Janssen Pharmaceutical Companies nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments. REFERENCES 1.     Gaine S, et al. Am J Respir Crit Care Med 2019;199: A2502. 2.     Vachiéry JL & Gaine S. Eur Respir Rev 2012;21:313–20. 3.     Hoeper MM, et al.Eur Respir J 2017;50:1700740. 4.     Sitbon O, et al. N Engl J Med 2015;373(26):2522–33. 5.     UPTRAVI (selexipag) Full Prescribing Information. Actelion Pharmaceuticals US, Inc. December 2017. 6.     UPTRAVI (selexipag) Summary of Product Characteristics. Janssen-Cilag International NV. November 2018. 7.     Galiè N, et al. Eur Heart J 2016;37:67–119. 8.     Hoeper MG, Gibbs SR. Eur Respir Rev 2014;23:450–7. CP-92263 May 2019 Logo: https://mma.prnewswire.com/media/889426/Actelion_Pharmaceuticals_Ltd_Logo.jpg