First Randomized Controlled Trial in Portopulmonary Hypertension Shows OPSUMIT® (macitentan) Significantly Improved Pulmonary Vascular Resistance Compared with Placebo
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
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.
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.
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.
Actelion Pharmaceuticals Ltd,
Office: +41 61-565-8980
Cell: +44 7973-824-614
Office: +41 61-565-5213
Cell: +41 792-198-643
Office: +1 732-524-3922
Office: +1 732-524-2955
Om Business Wire
(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
IFF and ISIPCA Celebrate First Master of Scent Design Graduating Class24.6.2019 20:15:00 CEST | Pressemelding
Regulatory News: IFF (NYSE:IFF) (Euronext Paris:IFF) (TASE:IFF), a leading innovator of taste, scent, and nutrition & ingredients, and ISIPCA, a prestigious higher education institution in the field of perfume, cosmetics, and flavoring, today celebrate the first Master of Scent Design and Creation graduating class of their collaborative program, established in 2016. “This is an historic day with many reasons to celebrate,” said Nicolas Mirzayantz, Scent Division CEO, IFF. “This is the first Masters of Scent Design & Creation graduating class from the first collaboration of its kind in the industry. We are thrilled at the sheer quality and passion of the well-trained and talented class, who are poised and ready to contribute to the world of fragrance. And we are happy to see such a diverse and inclusive group, reflecting the consumers for whom they will create.” The three-year program, based in Versailles, France, offers students a strong foundation in the art of perfumery, including an
3,900-Acre Wyoming “Holy Cow Ranch” Neighboring Bighorn National Forest to Auction via Concierge Auctions24.6.2019 19:58:00 CEST | Pressemelding
A 3,900-acre property located halfway between Yellowstone Park and Mount Rushmore in Sheridan, Wyoming – affectionately known as Holy Cow Ranch – will auction next month via leading global firm Concierge Auctions. The property features five structures including a guest lodge and owner’s residence, a pool with pool house, tennis courts, and miles of Bighorn National Forest frontage. Previously listed for $23.5 million, 43 Rapid Creek Road will auction Without Reserve in cooperation with Bruce Garber, Joe Steger, and Roger St Clair of Century 21 BHJ Realty, Inc. Bidding, which will be held via Concierge Auctions’ online marketplace, will open July 23rd and close July 26th. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20190624005652/en/ Holy Cow Ranch – Sheridan, WY (Photo: Business Wire) “The auction of Holy Cow Ranch presents the opportunity to own a truly impressive range of some of North America’s most beautiful landscapes,
Avioq Announces CE Mark and European Launch of VioOne HIV Profile Supplemental Assay24.6.2019 15:11:00 CEST | Pressemelding
Avioq, Inc. has received CE Marking (Conformité Européenne) and has begun marketing their VioOne™ HIV Profile™ Supplemental Assay in the European Union and other CE Mark countries. The product has also been submitted for FDA approval. “We are pleased to provide the CE Mark HIV Profile™ assay to countries outside the U.S.,” said Chamroen Chetty, CEO of Avioq. Dr. Chetty continues, “We are also looking for distribution partners to expand the global availability.” The HIV Profile™ is an enzyme-linked immunosorbent assay (ELISA) for confirmation and differentiation of individual antibodies directed to various gene products of HIV-1 (Group M & Group O) and HIV-2 in human serum or plasma that were repeatedly reactive in diagnostic screening procedures. Results can also be used to distinguish recent from longstanding HIV-1 infection for HIV-1 incidence estimation. About Confirmatory Testing In 2014, the CDC released a new algorithm for HIV testing. The second step of the algorithm includes a
Global Launch of S BLOCK, Kicked Off in Singapore on June 22nd24.6.2019 12:29:00 CEST | Pressemelding
The globally renowned 2019 WBF Singapore Technology Conference was held in Marina Bay Sands Hotel on June 22nd, 2019. S BLOCK, the conference co-host, unveiled itself and announce its mission to “Unleash your digital assets” for the first time. The conference brought together numerous industry elites and blockchain enthusiasts from all around the world, including more than 500 industry veterans from over 30 countries, such as Switzerland, Germany, France, Russia, Japan, Korea, Brazil, Australia, Argentina and Canada. Insiders shared profound global industry insights. This conference draws great attention from across the global blockchain industry. S BLOCK Kicked Off in Singapore In the morning of June 22nd, Ivan - President of S BLOCK Global Foundation, was invited to deliver a keynote speech, “Next Generation Digital Currency Wallet”. At this conference, S BLOCK was officially launched in more than 30 countries around the world, and opened up the way to a global future without borders
SpeeDx announce a collaborative agreement with GSK to supply tests and technology24.6.2019 12:00:00 CEST | Pressemelding
SpeeDx Pty. Ltd., a developer of innovative molecular diagnostic solutions, has signed a collaborative agreement with GSK, to provide a combination of existing tests and custom test development to support certain GSK antibiotic clinical trials and new product development. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20190624005302/en/ “SpeeDx has a demonstrated commitment to improve patient care, and our tests currently used in clinical practice are supporting Resistance Guided Therapy, positively impacting cure rates and helping to minimise the spread of antimicrobial resistant infections.” Colin Denver, SpeeDx CEO. (Photo: Business Wire) “We welcome this extension of the utility and application of our tests and technology,” said Colin Denver, SpeeDx CEO. “SpeeDx has a demonstrated commitment to improve patient care, and our tests currently used in clinical practice are supporting Resistance Guided Therapy, positively impac
Nexon Computer Museum to Hold the Fourth VR Content Contest24.6.2019 10:13:00 CEST | Pressemelding
Nexon Computer Museum (NCM) of NXC is holding the fourth virtual reality content contest, ‘2019 NCM OPEN CALL X REALITY’. NXC is a holding company of Nexon (TOKYO: 3659). This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20190624005284/en/ Nexon Computer Museum (NCM) of NXC is holding the fourth virtual reality content contest 2019 NCM OPEN CALL X REALITY with total prize money of KRW 13 million. Application received from July 1st to August 31st, winners announced on October 25th. (Graphic: Business Wire) NCM OPEN CALL is an exhibit to discover and support virtual reality content creators. This year’s keyword ‘X REALITY’ encompasses all kinds of virtualization including VR, AR, MR, and more. It also implies eXtended Reality, which broadens the perspectives of reality, and Cross Reality, which overlaps the real and virtual world. The unpredictable X signifies NCM OPEN CALL’s pursuit towards embracing various kinds of innovative an