Actelion Submits Application to EMA Seeking Approval of OPSUMIT® (macitentan) for the Treatment of Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
Actelion Pharmaceuticals Ltd, one of the Janssen Pharmaceutical Companies of Johnson & Johnson, today announced the submission of a Type II Variation to the European Medicines Agency (EMA) seeking to expand the indication of OPSUMIT® (macitentan) to include the treatment of adults with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) of WHO Functional Class (FC) II to III to improve exercise capacity.
CTEPH is a rare form of pulmonary hypertension (PH) and a life-threatening complication of pulmonary embolism in which scar-like tissue forms around unresolved blood clots in the lungs which block or narrow the arteries. Without intervention or treatment, the disease continues to progress, eventually resulting in right ventricular failure (heart failure) and subsequently death1.
Surgery to clear the blockages in the lungs is the preferred treatment option for CTEPH and is potentially curative2,3. However, a substantial proportion (up to 50%) of CTEPH patients are deemed inoperable4 and current pharmacological treatment options for these patients are limited to one licensed therapy only5,6.
If approved, OPSUMIT would be the first therapy in its class (endothelin receptor antagonists or ERA) available in the EU for the treatment of inoperable CTEPH.
“MERIT-1 provides the first randomized controlled trial data involving patients on monotherapy and combination therapy, addressing a key unmet need in CTEPH,” said Martin Fitchet, M.D., Global Head, Actelion Research & Development, Janssen Research & Development, LLC. “If approved, OPSUMIT has the potential to become a valuable treatment option in inoperable CTEPH. Building on its 20-year heritage of unprecedented innovation in pulmonary hypertension, Actelion is committed to addressing the unmet needs that persist in this severe and life-limiting disease. Ultimately our vision is to transform pulmonary hypertension into a chronic, manageable condition.”
The filing is based on data from the randomized clinical trial, MERIT-1 which showed significant improvements in the primary and secondary endpoints of pulmonary vascular resistance (PVR) and six-minute walk distance (6MWD), respectively, for patients treated with macitentan compared with placebo7. The benefits of macitentan were seen irrespective of whether patients were receiving treatment with other PAH therapies at baseline (most commonly phosphodiesterase type 5 [PDE5] inhibitors)7. Macitentan was well tolerated in this patient population and safety was generally consistent with the known safety profile for macitentan from previous clinical studies in PAH7. The study results were presented at the American Thoracic Society (ATS) 2017 and European Respiratory Society (ERS) 2017 and published in The Lancet Respiratory Medicine.
OPSUMIT is an orally active ERA that is currently approved in the EU as monotherapy or in combination for the long-term treatment of pulmonary arterial hypertension (PAH) in adult patients of WHO FC II to III8. In July this year, the US Food and Drug Administration (FDA) accepted for review Actelion’s supplemental New Drug Application for OPSUMIT for the treatment of adults with inoperable CTEPH to improve exercise capacity and pulmonary vascular resistance (PVR).
Notes to the Editor
ABOUT CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION (CTEPH)
CTEPH is a unique form of pulmonary hypertension (PH) caused by chronic obstruction of the pulmonary arteries. The obstructions can result from blood clots that become stuck to the walls of the pulmonary arteries. The lining of the pulmonary arteries then begins to form excess tissue around the clots, transforming them into fibrous scar tissue that is attached to the artery wall. This creates a blockage that restricts the blood flow and increases the blood pressure, causing pulmonary hypertension and chronic stress to the right side of the heart – with the risk of developing right-side heart failure over time1.
In total, just over 2,600 patients are estimated to be diagnosed with CTEPH each year across France, Germany, Italy, Spain and the UK, although the actual incidence is thought to be higher9.
Pulmonary thromboendarterectomy (PEA) remains the preferred treatment for CTEPH. However, certain CTEPH patients are not operative candidates due to the nature of the disease, location of the thrombi or multiple co-morbid conditions4. New medical treatment options are therefore needed for the effective management of this patient group.
ABOUT THE MERIT-1 STUDY
MERIT-1 (Macitentan in the treatment of Inoperable chronic Thromboembolic pulmonary hypertension) was a prospective, randomized, placebo-controlled, double-blind, multicenter, parallel-group study to assess the efficacy, safety and tolerability of 10mg macitentan in patients with inoperable CTEPH.
In MERIT-1, 80 inoperable patients (WHO Functional Class [FC] II to IV) were randomized in a 1:1 ratio into two treatment groups (macitentan 10mg or placebo) over a 24-week treatment period. The study started in August 2014 and was completed in September 2016. Patients with symptomatic PH in WHO FC III or IV at baseline were allowed to receive PAH background therapy throughout the study, including phosphodiesterase type 5 (PDE5) inhibitors and/or oral/inhaled prostanoids. All patients included in the study underwent independent operability assessment based on local or central adjudication committees.
After 16 weeks of treatment, there was a significant reduction in the primary endpoint, pulmonary vascular resistance (PVR) for macitentan compared with placebo (p=0.041). The efficacy observed was consistent across all sub-groups, including patients receiving background PAH specific therapy at baseline (61% of patients), including PDE5 inhibitors (59% of patients).
The study also showed a significant positive effect of macitentan compared to placebo on exercise capacity, one of the secondary endpoints. After 24 weeks of treatment, the mean change in 6MWD from baseline was an increase of 35 meters in patients treated with macitentan and 1 meter in those receiving placebo (p=0.033).
Macitentan was well tolerated in this patient population and safety was in general consistent with the known safety profile for macitentan from previous clinical studies. The most frequently (≥10%) reported adverse events that occurred with higher frequency on macitentan vs. placebo were peripheral edema (23% vs. 10.0%) and decrease in hemoglobin (15% vs. 0%).
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 progression10.
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 PAH10.
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 III8.
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 disease8.
OPSUMIT is very likely to cause major birth defects. It is contraindicated for use in pregnancy. In the U.S., OPSUMIT is distributed under a risk evaluation and mitigation strategy (REMS)10.
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. Medrek S and Safdar Z. Methodist Debakey Cardiovasc J 2016;
2. Galie N, et al. Eur Respir J 2015; 46:903-75.
3. Madani M, et al. Ann Am Thorac Soc 2016; 13 Suppl 3:S240-7.
4. Madani M, et al. Eur Respir Rev 2017; 26:170105.
5. Kim NH, et al. Heart 2017; 103:599-606.
6. Ghofrani HA, et al. N Engl J Med 2013; 369:319-29.
7. Ghofrani HA, et al. Lancet Respir Med 2017; 5:785-94.
8. OPSUMIT (macitentan) Summary of Product Characteristics. Actelion Pharmaceuticals Ltd.
9. Gall H, et al. Eur Respir Rev 2017; 26:160121.
10. OPSUMIT (macitentan) full Prescribing Information. Actelion Pharmaceuticals US, Inc.
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
Project Management Institute Launches New Reports on Navigating the New Normal of Disruptive Technologies During Seventh Annual PMO Symposium®12.11.2018 16:43 | Pressemelding
Project Management Institute (PMI) today unveiled three thought leadership reports focused on navigating the new normal of disruptive technologies. The new reports were released during the organization’s seventh annual PMO Symposium® in Washington D.C., where more than 650 of the world’s top project management office (PMO) executives, organizational leaders and senior decision makers have gathered to discuss how disruptive technologies—such as cloud solutions, internet of things (IoT) and artificial intelligence (AI)—have changed the way organizations do business and transformed entire industries. Throughout 2018, PMI and partners, have been exploring disruptive technologies and how organizations are using them to achieve their goals in these changing times. While no one single factor can drive benefits realization, leading organizations understand that proven project management practices lead to greater success and less waste. Produced in partnership with Accenture, PMI’s report — For
Separate Independent Studies Found that PREVENA™ Therapy Reduced Complications Following Breast Cancer Surgery and Breast Reconstruction12.11.2018 14:00 | Pressemelding
KCI, an Acelity Company, announced today that recently published data stemming from two studies demonstrate that closed incision negative pressure therapy (ciNPT) with the PREVENA™ Incision Management System reduced postsurgical wound complication potential in patients recovering from oncological breast surgery and breast reconstruction, respectively. One study titled, “The Impact of Closed Incision Negative Pressure Therapy on Postoperative Breast Reconstruction Outcomes,” showed that patients who received ciNPT with the PREVENA™ System had significantly lower rates of overall complications and returns to the operating room compared to those in the standard of care (SOC) for incision management after breast reconstruction post-mastectomy group. In addition, patients in the PREVENA™ Therapy group overall had a shorter mean time to complete removal of all drains than the SOC group, averaging 9.9 days versus 13.1, respectively.1 In a separate study titled, “Closed Incision Negative Press
Itron Invites Innovators to Participate in Smart City Challenge12.11.2018 13:45 | Pressemelding
Itron, Inc. (NASDAQ: ITRI) is calling for hardware and software vendors to submit their products and solutions to the inaugural Itron Smart City Challenge. IoT solution providers will compete for the chance to work with leading smart cities, including Glasgow and the City of London, to deploy breakthrough solutions. Applications are due by Jan. 4, 2019. Participants are invited to develop solutions to address challenges defined by the participating cities. Glasgow: Improve travel choices and experience during events in the city while promoting the overall city center offer The City of Glasgow is one of the world’s top sporting cities and a major destination for conferences and concerts. Many thousands of people come to the city on a regular basis to experience its year-round calendar of events. However, this brings significant challenges in getting people safely and conveniently around the city to their location. It also impacts residents and particularly, the public transport system.
US-Based Lineage Logistics Acquires UK Cold Storage, Frozen Food and Logistics Service Provider Yearsley Group12.11.2018 12:00 | Pressemelding
Lineage Logistics Holdings, LLC (“Lineage” or the “Company”), the world’s most innovative and trusted provider of temperature-controlled supply chain solutions, today announced it has acquired Yearsley Group Limited (“Yearsley”), a leading temperature-controlled logistics service provider and frozen food distributor in the UK. Financial terms of the transaction were not disclosed. “Yearsley has demonstrated a strong commitment to developing longstanding, bespoke customer relationships that is consistent with how we do business at Lineage. Bringing Yearsley into the Lineage family enables us to better serve customers in the UK market and further reinforces our international logistics capabilities,” said Greg Lehmkuhl, President and Chief Executive Officer of Lineage Logistics. “Our acquisition by Lineage is a tremendous opportunity for Yearsley customers and employees alike,” said Jonathan Baker, Chief Executive of Yearsley Group. “Lineage’s commitment to innovation and service is unmat
B2BX Cryptocurrency Exchange Secures Full Regulatory Approval in Estonia12.11.2018 09:29 | Pressemelding
B2BX Exchange, a leading professional digital asset trading platform, announced today that it has received approval for a regulatory licence from the Estonian Financial Intelligence Unit (FIU). The licence means that B2BX will be able to operate as a completely regulated exchange for trading cryptocurrencies and makes it one of the first exchanges in Europe to secure this form of recognition. B2BX Exchange, part of the B2Broker group of companies, applied for its licence in Estonia due to the country’s reputation for being highly innovative and technology-friendly. Furthermore, the EU-member country continues to take a leading stance in the advancement of blockchain technologies and cryptocurrency regulation. The licence, which comes into effect shortly, will open the door for B2BX Exchange to provide an extended level of services which currently includes a crypto-to-crypto service and soon to be crypto-to-fiat, as well as providing peace of mind for B2BX Exchange users by way of incre
GSMA Elects New Board Members and Announces Orange Chairman and CEO Stéphane Richard as Chair12.11.2018 09:00 | Pressemelding
The GSMA today announced that it has elected new members of the GSMA Board for the two-year period from January 2019 through December 2020. The GSMA Board has also elected Stéphane Richard, Chairman and Chief Executive Officer of Orange Group as Chair, and Chua Sock Koong, Group Chief Executive Officer of Singtel Group as Deputy Chair. As GSMA Chair, Richard will oversee the strategic direction of the organisation, which represents more than 750 of the world’s mobile operators, as well as over 350 companies in the broader mobile ecosystem. “I am honoured to be elected to serve as Chair of the GSMA and look forward to working closely with the rest of the Board, the GSMA leadership team and our entire membership to address the critical issues facing our industry and our customers,” said Stéphane Richard, Chairman and Chief Executive Officer of Orange. “Mobile operators and our wider industry have a key role to play in promoting a safer and more inclusive digital world, while building the