Business Wire

First Randomized Controlled Trial in Portopulmonary Hypertension Shows OPSUMIT® (macitentan) Significantly Improved Pulmonary Vascular Resistance Compared with Placebo

Del

Actelion Pharmaceuticals Ltd, one of the Janssen Pharmaceutical Companies of Johnson & Johnson, has announced the results of the first randomized controlled trial in portopulmonary hypertension (PoPH), which showed OPSUMIT® (macitentan) significantly improved pulmonary vascular resistance (PVR) compared with placebo, meeting the primary endpoint of the study. Presented as a late-breaking oral presentation at the European Respiratory Society (ERS) meeting in France, the PORtopulmonary hypertension Treatment wIth maCitentan ─ a randOmized clinical trial (PORTICO) showed the safety of macitentan in PoPH was consistent with that observed in previous clinical trials.

PoPH is a subset of pulmonary arterial hypertension (PAH), associated with portal hypertension (increased blood pressure in the portal vein)1 often due to cirrhosis2. PoPH is increasingly recognized and evidence suggests that it is the fourth most common form of PAH3. In many cases, patients with PoPH are only diagnosed as part of an assessment for liver transplantation; however, severe PAH is a contraindication for liver transplant due to poor post-operative prognosis4.

"The findings of PORTICO are relevant because if patients with PoPH can be treated to successfully lower pulmonary vascular pressure and resistance, more patients may be eligible for liver transplant as they will potentially have a better prognosis for this surgery,” said the lead investigator, Olivier Sitbon, MD, PhD, Professor of Respiratory Medicine at the South Paris University. “The fact that the hepatic safety profile of macitentan in patients with PoPH was consistent with that observed in previous trials is particularly reassuring, as PoPH patients are typically excluded from PAH clinical trials on safety grounds.”

Data supporting the use of PAH therapies in PoPH are extremely limited and are mostly from single-center, open-label studies5-7. To date, none of the approved PAH treatments have been shown to improve cardiopulmonary hemodynamics in PoPH in a randomized controlled clinical trial.

In the PORTICO trial8, patients were randomized to receive macitentan 10mg (n=43) or placebo (n=42) once daily. After 12 weeks of treatment, macitentan significantly improved PVR (primary endpoint met, 35% reduction vs placebo, p<0.0001), mean pulmonary arterial pressure (mPAP; macitentan reduced mPAP by 5.99 mmHg vs placebo, p<0.0001) and cardiac index (macitentan increased cardiac index by 0.52 L/min/m2 vs placebo, p=0.0009)9.

There was no significant difference between macitentan and placebo groups in six-minute walk distance (6MWD) or WHO Functional Class (FC). The most common adverse events (macitentan vs placebo) were peripheral edema (25.6 vs 11.9%) and headache (16.3 vs 16.7%)9.

OPSUMIT is an orally active endothelin receptor antagonist (ERA) that is currently approved in the US and Europe for the treatment of PAH10,11.

###

Notes to the Editor

ABOUT PORTOPULMONARY HYPERTENSION (PoPH)
PoPH is a form of pulmonary arterial hypertension (PAH) associated with portal hypertension with or without underlying chronic liver disease12. However, as cirrhosis is the most common cause of portal hypertension, advanced liver disease is often encountered in patients with PoPH2.

The symptoms associated with PoPH are similar, if not identical, to most other forms of PAH. They 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 expectancy4. The diagnosis of PoPH is often only made as part of an assessment for liver transplantation4, which can lead to a significant delay in diagnosis and patient care.

To date, no other approved PAH treatment besides OPSUMIT has demonstrated benefit in PoPH in a dedicated randomized controlled clinical trial.

ABOUT THE PORTICO STUDY 9
PORTICO (PORtopulmonary hypertension Treatment wIth maCitentan ─ a randOmized clinical trial) is a Phase IV, prospective, randomized, placebo-controlled, double-blind, multicenter, parallel-group study to assess the efficacy and safety of macitentan 10 mg in patients with PoPH.

In PORTICO, 85 patients with a confirmed diagnosis of PoPH were randomized in a 1:1 ratio into two treatment groups (macitentan 10mg or placebo) over a 12-week double-blind treatment period. The study started in June 2015 and was completed in October 2017.

The study met its primary endpoint; after 12 weeks of treatment, there was a significant reduction of 35% in pulmonary vascular resistance (PVR) for macitentan compared with placebo (geometric mean ratio [95% CI]: 0.65 [0.59, 0.72] p<0.0001).

The study also showed a significant positive effect of macitentan compared with placebo on mean pulmonary arterial pressure (mPAP) and cardiac index. After 12 weeks of treatment, macitentan significantly improved mPAP (macitentan reduced mPAP by 5.99 mmHg vs placebo, p<0.0001) and cardiac index (macitentan increased cardiac index by 0.52 L/min/m2 vs placebo, p=0.0009). There was no significant difference between groups in change from baseline for six-minute walk distance (6MWD) or WHO Functional Class (FC).

Macitentan was well tolerated in this patient population and safety was in general consistent with the known safety profile for the treatment from previous clinical studies. The most frequently (≥10%) reported adverse events (macitentan vs placebo) were peripheral edema (25.6 vs 11.9%) and headache (16.3 vs 16.7%). There was a mean decrease in hemoglobin with macitentan of 1.8 g/dL. No patients discontinued the study due to liver enzyme elevations, and only one patient treated with macitentan experienced alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≥3x upper limit of normal.

ABOUT OPSUMIT (macitentan)
OPSUMIT, an orally available endothelin receptor antagonist, resulted from a tailored drug discovery process in Actelion's laboratories.

In the US, OPSUMIT is indicated for the treatment of PAH, WHO Group I to delay disease progression11.

Disease progression included: death, initiation of intravenous (IV) or subcutaneous prostanoids, or clinical worsening of PAH (decreased 6-minute walk distance, worsened PAH symptoms and need for additional PAH treatment). OPSUMIT also reduced hospitalization for PAH11.

In Europe, OPSUMIT is indicated, as monotherapy or in combination, for the long-term treatment of PAH in adult patients of WHO Functional Class (FC) II to III10.

The effectiveness of OPSUMIT was established in a long-term study in PAH patients with predominantly WHO FC II-III symptoms treated for an average of two years. Patients were treated with OPSUMIT monotherapy or in combination with PDE5 inhibitors or inhaled prostanoids. 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 disease10.

OPSUMIT is very likely to cause major birth defects. In both the US and Europe, it is contraindicated for use in pregnancy10,11. In Europe, contraindications for OPSUMIT also include patients with severe hepatic impairment and those with elevated aminotransferase levels three times upper limit of normal; it is also not recommended in patients with moderate hepatic impairment. Liver enzyme tests should be obtained prior to initiation of OPSUMIT10. Patients should be monitored for signs of hepatic injury and monthly monitoring of ALT and AST is recommended10. In the US, OPSUMIT is distributed under a risk evaluation and mitigation strategy (REMS); baseline liver enzymes should be obtained and patients treated with OPSUMIT should be monitored as clinically indicated11.

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 at @actelion_com.

ABOUT THE JANSSEN PHARMACEUTICAL COMPANIES OF JOHNSON & JOHNSON
At the Janssen Pharmaceutical Companies of Johnson & Johnson, we are working to create a world without disease. Transforming lives by finding new and better ways to prevent, intercept, treat and cure disease inspires us. We bring together the best minds and pursue the most promising science. We are Janssen. We collaborate with the world for the health of everyone in it. Actelion Pharmaceuticals Ltd is one of the Janssen Pharmaceutical Companies of Johnson & Johnson. Learn more at www.janssen.com. Follow us at www.twitter.com/JanssenUS and www.twitter.com/JanssenGlobal.

Cautions Concerning Forward-Looking Statements

This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding OPSUMIT® (macitentan). 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 31 December, 2017, 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. Neither 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. Krowka MJ, et al. Chest 2012; 141:906-15.
2. Medarov BI, et al. Respir Med 2014; 108:943-54.
3. Humbert M, et al. Am J Respir Crit Care Med 2006; 173:1023-30.
4. Galiè N, et al. Eur Heart J 2016; 37:67-119.
5. Krowka MJ, et al. Hepatology 1999; 30:641-8.
6. Cartin-Ceba R, et al. Chest 2011; 139:109-14.
7. Savale L, et al. Eur Respir J 2013; 41:96-103.
8. NCT02382016; PORTICO; https://www.clinicaltrials.gov.
9. Sitbon O, et al. Efficacy and safety of macitentan in portopulmonary hypertension: the PORTICO trial. European Respiratory Society International Congress 2018; OA267.
10. OPSUMIT (macitentan) Summary of Product Characteristics. Actelion Pharmaceuticals Ltd. February 2018.
11. OPSUMIT (macitentan) full Prescribing Information. Actelion Pharmaceuticals US, Inc. March 2017.
12. Saleemi S. Ann Thorac Med 2010; 5:5-9.

Contact information

Actelion Pharmaceuticals Ltd,
Media Contact
David Keown
Office: +41 61-565-8980
Cell: +44 7973-824-614
DKeown@its.jnj.com
or
Tina Kitt
Office: +41 61-565-5213
Cell: +41 792-198-643
CKitt@its.jnj.com
or
Investor Contact
Lesley Fishman
Office: +1 732-524-3922
LFishma@its.jnj.com
or
Christopher DelOrefice
Office: +1 732-524-2955
CDeloref@its.jnj.com

Om Business Wire

Business Wire
Business Wire
24 Martin Lane
EC4R 0DR London

+44 20 7626 1982http://www.businesswire.co.uk

(c) 2018 Business Wire, Inc., All rights reserved.

Business Wire, a Berkshire Hathaway company, is the global leader in multiplatform press release distribution.

Følg saker fra Business Wire

Registrer deg med din epostadresse under for å få de nyeste sakene fra Business Wire på epost fortløpende. Du kan melde deg av når som helst.

Siste saker fra Business Wire

Grand Prize Winner in $1.75M Water Abundance XPRIZE Announced at XPRIZE Visioneering 201822.10.2018 17:49Pressemelding

During Visioneering 2018, XPRIZE’s annual gathering of philanthropists and innovators to evaluate concepts for future competitions, the Foundation revealed the results of its latest, completed XPRIZE. The Skysource / Skywater Alliance was announced as the grand prize winner of the $1.75M Water Abundance XPRIZE, a two-year competition aimed at alleviating the global water crisis with energy-efficient technologies that harvest fresh water from thin air. In addition at Visioneering, five new prize concepts were evaluated with top honors going to a prize concept called “Coral Survival”, a prize designed to protect and restore coral reefs. This prize will move forward into the XPRIZE pipeline. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20181022005795/en/ The Skysource / Skywater Alliance team, based in Venice Beach, California, wins the Water Abundance XPRIZE (Photo: Business Wire) The Water Abundance XPRIZE, powered by the Tat

Positive Trial Results with Filgotinib in Psoriatic Arthritis and Ankylosing Spondylitis Both Published in The Lancet22.10.2018 17:15Pressemelding

Gilead Sciences, Inc. (Nasdaq: GILD) and Galapagos NV (Euronext & NASDAQ: GLPG) today announced that detailed results from two clinical trials evaluating filgotinib, an investigational, selective JAK1 inhibitor, for the treatment of psoriatic arthritis and ankylosing spondylitis were both published in The Lancet. The publication of the Phase 2 EQUATOR data also coincides with a plenary session presentation at the 2018 American College of Rheumatology/Association of Rheumatology Health Professionals (ACR/ARHP) Annual Meeting. “The results of the EQUATOR and TORTUGA studies demonstrate that filgotinib improved the signs and symptoms of patients with psoriatic arthritis whose disease had not responded to prior therapies and independently, for those with ankylosing spondylitis,” said John McHutchison, AO, MD, Chief Scientific Officer and Head of Research and Development, Gilead Sciences. “These findings represent an important step forward in our efforts to improve outcomes for people livin

First Data Polska Deploys Inside Secure’s Mobile Payment Technology To Securely and Easily Connect to Mastercard and Visa22.10.2018 15:36Pressemelding

Regulatory News: Inside Secure (Paris:INSD) (Euronext Paris: INSD), at the heart of security solutions for mobile and connected devices, today announced that First Data Polska S.A., a division of the global leader in commerce-enabling technology, selected Inside Secure technology to enable secure and flexible connections to Mastercard and Visa. First Data Polska S.A. chose Inside Secure’s Mobile Payment Client to easily integrate their solution with the Visa Token Service (VTS) and Mastercard Digital Enablement Service (MDES) – today’s major tokenization services that convert sensitive data into unique tokens that allow mobile payments to be processed. “Security and reliability are continual requirements for our services,” said Jolanta Rycerz, Member of Management Board at First Data Polska S.A. “We see Inside Secure as a valuable technology provider that enables us to easily migrate to the latest mobile payment technology and security standards. Thanks to Inside Secure, our customers,

PMI Launches Search for Next President and CEO22.10.2018 14:00Pressemelding

Project Management Institute (PMI), the world’s leading professional membership organization for project managers, announced today that it has retained Heidrick & Struggles to help the organization find its next President and Chief Executive Officer (CEO). The dynamic leader shall oversee the implementation of a new strategic plan and guide the organization toward a future designed to help thousands of project professionals around the world accelerate their careers and make ideas a reality. Heidrick & Struggles is a premier provider of executive search, leadership assessment and development, organization and team effectiveness, and culture shaping services globally. PMI will conduct a comprehensive global review of both internal and external candidates for this key position. The selected candidate will embody PMI’s core values and possess the skillsets necessary to advance the organization’s key goals. PMI’s next President and CEO will help it execute a bold new multi-year initiative d

E2open to Acquire INTTRA, Adding the World’s Leading Ocean Shipping Network and Software Provider, Creating an Integrated Global Supply Chain and Logistics Operating Network22.10.2018 13:43Pressemelding

E2open, the one place in the cloud to run your supply chain, today announced the acquisition of INTTRA, the leading ocean shipping network, software and information provider. The combination of INTTRA’s ocean carrier and shipper network with E2open’s industry leading business network will create a unified global logistics and supply chain network. E2open and INTTRA will join efforts to strengthen the connections and streamline the information flow between manufacturers, suppliers, shipping service providers, ocean carriers and all the participants in global trade. E2open is the largest cloud-based provider of networked supply chain solutions, featuring a complete portfolio of applications that enable the world’s most complex supply chains to better plan, collaborate, and execute their end-to-end operations. More than 70,000 partner companies and 200,000 users, many of the biggest brands and manufacturers across a range of industries, use the E2open network and platform to orchestrate t

Patient-Data Platform Raremark Raises £3m to Enable Precision Medicine in Rare Disease22.10.2018 12:00Pressemelding

Raremark, the leading patient-data platform in rare disease, has raised £3m in funding from investors, led by AlbionVC and Ananda Ventures, with participation from Oltre Venture and from existing major investor the Cass Entrepreneurship Fund. The funding will be used to develop Raremark’s patient-engagement and data-analysis technology, helping biopharmaceutical companies to identify, engage and learn from patients, accelerating the development of new treatments. Raremark’s platform is the foundation for building research networks of rare disease patients and their families. Raremark provides biopharmaceutical companies with access to anonymized and aggregated patient data, helping to reduce the time and cost of clinical development. The Raremark platform engages and retains patients, leveraging machine-learning technologies in novel ways. The approach is designed to raise health literacy and informed participation in medical research, to improve the quality of existing therapies and t