Ipsen Announces That Phase 3 CELESTIAL Trial of Cabozantinib Meets Primary Endpoint of Overall Survival in Patients with Advanced Hepatocellular Carcinoma
Ipsen (Euronext: IPN; ADR: IPSEY) and its partner Exelixis (NASDAQ: EXEL) today announced that its global phase 3 CELESTIAL trial met its primary endpoint of overall survival (OS), with cabozantinib providing a statistically significant and clinically meaningful improvement in median OS compared to placebo in patients with advanced hepatocellular carcinoma (HCC). The independent data monitoring committee for the study recommended that the trial should be stopped for efficacy following review of the second planned interim analysis. CELESTIAL is a randomized, global phase 3 trial of cabozantinib versus placebo in patients with advanced HCC who have been previously treated with sorafenib. The safety data in the study were consistent with the established profile of cabozantinib.
In line with and in collaboration with our partner Exelixis, Ipsen expects to file in the first half of 2018 a variation of the initial application to the EMA and other relevant regulatory agencies and to evaluate potential next steps in the development strategy for cabozantinib outside the United States and Japan as a treatment for advanced HCC in patients who have been previously treated. Detailed results from CELESTIAL will be submitted for presentation at a future medical conference.
Alexandre Lebeaut, MD, Executive Vice-President, R&D, Chief Scientific Officer, Ipsen, said: “Liver cancer is one of the leading causes of cancer deaths worldwide and more effective treatment options are urgently needed. We are pleased to report that in the CELESTIAL clinical study cabozantinib has been shown to provide a survival benefit and therefore has the potential to bring a new oral systemic treatment to previously treated patients with advanced liver cancer. ”
About the CELESTIAL Study
CELESTIAL is a randomized, double-blind, placebo-controlled study of cabozantinib in patients with advanced HCC conducted at more than 100 sites globally in 19 countries. The trial was designed to enroll 760 patients with advanced HCC who previously received sorafenib and may have received up to two prior systemic cancer therapies for HCC and had adequate liver function. Enrollment of the trial was completed in September 2017, and 773 patients were ultimately randomized. Patients were randomized 2:1 to receive 60 mg of cabozantinib once daily or placebo and were stratified based on etiology of the disease (hepatitis C, hepatitis B or other), geographic region (Asia versus other regions) and presence of extrahepatic spread and/or macrovascular invasion (yes or no). No cross-over was allowed between the study arms.
The primary endpoint for the trial is OS, and secondary endpoints include objective response rate and progression-free survival. Exploratory endpoints include patient-reported outcomes, biomarkers and safety.
Based on available clinical trial data from various published trials conducted in the second-line setting of advanced HCC, the CELESTIAL trial statistics for the primary endpoint of OS assumed a median OS of 8.2 months for the placebo arm. A total of 621 events provide the study with 90 percent power to detect a 32 percent increase in median OS (HR = 0.76) at the final analysis. Two interim analyses were planned and conducted at 50 percent and 75 percent of the planned 621 events.
Hepatocellular Carcinoma (HCC) is the most common form of liver cancer in adults.1 The disease originates in cells called hepatocytes found in the liver. With approximately 800’000 new cases diagnosed each year, HCC is the sixth most common cancer and the second-leading cause of cancer deaths worldwide.2,3 According to the GLOBOCAN data, it is estimated that across the European Union (EU-28) nearly 60’000 new patients will be diagnosed with liver cancer in 2020.4 Without treatment, patients with the disease in advanced stage usually survive between 4 and 8 months.5
Cabometyx® is an oral small molecule inhibitor of receptors, including VEGFR, MET, AXL and RET. In preclinical models, cabozantinib has been shown to inhibit the activity of these receptors, which are involved in normal cellular function and pathologic processes such as tumor angiogenesis, invasiveness, metastasis and drug resistance.
In February of 2016, Exelixis and Ipsen jointly announced an exclusive licensing agreement for the commercialization and further development of cabozantinib indications outside of the United States, Canada and Japan. This agreement was amended in December of 2016 to include commercialization rights for Ipsen in Canada. On April 25, 2016, the FDA approved Cabometyx® tablets for the treatment of patients with advanced RCC who have received prior anti-angiogenic therapy and on September 9, 2016, the European Commission approved Cabometyx® tablets for the treatment of advanced RCC in adults who have received prior vascular endothelial growth factor (VEGF)-targeted therapy in the European Union, Norway and Iceland. Cabometyx® is available in 20 mg, 40 mg or 60 mg doses. The recommended dose is 60 mg orally, once daily.
Ipsen also submitted to European Medicines Agency (EMA) the regulatory dossier for cabozantinib as a treatment for first-line advanced RCC in the European Union on August 28, 2017; on September 8, 2017, Ipsen announced that the EMA validated the application.
Cabozantinib is not approved for the treatment of advanced hepatocellular carcinoma.
Ipsen is a global specialty-driven biopharmaceutical group focused on innovation and specialty care. The group develops and commercializes innovative medicines in three key therapeutic areas - Oncology, Neurosciences and Rare Diseases. Its commitment to oncology is exemplified through its growing portfolio of key therapies for prostate cancer, neuroendocrine tumors, renal cell carcinoma and pancreatic cancer. Ipsen also has a well-established Consumer Healthcare business. With total sales close to €1.6 billion in 2016, Ipsen sells more than 20 drugs in over 115 countries, with a direct commercial presence in more than 30 countries. Ipsen's R&D is focused on its innovative and differentiated technological platforms, and centers located in the heart of leading biotechnological and life sciences hubs (Paris-Saclay, France; Oxford, UK; Cambridge, US). The Group has about 5,100 employees worldwide. Ipsen is listed in Paris (Euronext: IPN) and in the United States through a Sponsored Level I American Depositary Receipt program (ADR: IPSEY). For more information on Ipsen, visit www.ipsen.com.
Forward Looking Statement
The forward-looking statements, objectives and targets contained herein are based on the Group’s management strategy, current views and assumptions. Such statements involve known and unknown risks and uncertainties that may cause actual results, performance or events to differ materially from those anticipated herein. All of the above risks could affect the Group’s future ability to achieve its financial targets, which were set assuming reasonable macroeconomic conditions based on the information available today. Use of the words "believes," "anticipates" and "expects" and similar expressions are intended to identify forward-looking statements, including the Group’s expectations regarding future events, including regulatory filings and determinations. Moreover, the targets described in this document were prepared without taking into account external growth assumptions and potential future acquisitions, which may alter these parameters. These objectives are based on data and assumptions regarded as reasonable by the Group. These targets depend on conditions or facts likely to happen in the future, and not exclusively on historical data. Actual results may depart significantly from these targets given the occurrence of certain risks and uncertainties, notably the fact that a promising product in early development phase or clinical trial may end up never being launched on the market or reaching its commercial targets, notably for regulatory or competition reasons. The Group must face or might face competition from generic products that might translate into a loss of market share. Furthermore, the Research and Development process involves several stages each of which involves the substantial risk that the Group may fail to achieve its objectives and be forced to abandon its efforts with regards to a product in which it has invested significant sums. Therefore, the Group cannot be certain that favorable results obtained during pre-clinical trials will be confirmed subsequently during clinical trials, or that the results of clinical trials will be sufficient to demonstrate the safe and effective nature of the product concerned. There can be no guarantees a product will receive the necessary regulatory approvals or that the product will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Other risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the Group's ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the Group’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions. The Group also depends on third parties to develop and market some of its products which could potentially generate substantial royalties; these partners could behave in such ways which could cause damage to the Group’s activities and financial results. The Group cannot be certain that its partners will fulfil their obligations. It might be unable to obtain any benefit from those agreements. A default by any of the Group’s partners could generate lower revenues than expected. Such situations could have a negative impact on the Group’s business, financial position or performance. The Group expressly disclaims any obligation or undertaking to update or revise any forward looking statements, targets or estimates contained in this press release to reflect any change in events, conditions, assumptions or circumstances on which any such statements are based, unless so required by applicable law. The Group’s business is subject to the risk factors outlined in its registration documents filed with the French Autorité des Marchés Financiers.
The risks and uncertainties set out are not exhaustive and the reader is advised to refer to the Group’s 2016 Registration Document available on its website (www.ipsen.com).
1. McGlynn KA, London WT. The Global Epidemiology of Hepatocellular
Carcinoma, Present and Future. Clinics in liver disease.
2. Ferlay J, Soerjomataram I, Dikshit R, et al: Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136:E359-86, 2015
3. GLOBOCAN International Agency for Research on Cancer (IARC). Available at: http://gco.iarc.fr/today/fact-sheets-cancers?cancer=7&type=0&sex=0
4. GLOBOCAN International Agency for Research on Cancer (IARC). Available at: http://globocan.iarc.fr/Pages/burden_sel.aspx
5. Annals of Oncology 23 (Supplement 7): vii41–vii48, 2012
Ian Weatherhead, Tél.: +44 (0) 7584230549
Vice-President, Corporate External communications
Brigitte Le Guennec, Tel.: +33 (0)1 58 33 51 17
Corporate External Communication Manager
E-mail : email@example.com
Eugenia Litz, Tel.: +44 (0) 1753 627721
Vice-President Investor Relations
Côme de La Tour du Pin, Tel.: +33 (0)1 58 33 53 31
Investor Relations Manager
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
Pre-Registration for MapleStory 2 Starts Today24.9.2018 17:00 | Pressemelding
Pre-registration for MapleStory 2, the newest MMORPG adventure in Maple World, is available starting today. From September 24 through October 8, players can sign-up on the MapleStory 2 Pre-Registration site available here and earn exclusive rewards! Pre-registration web rewards will include unique in-game items such as the Roosting Seagull, Rustic Mushcabin Name Tag, and the Dusty Rickshaw. From September 24 through October 8, players can also receive a Mint Body Pillow by retweeting the new Runeblade trailer on Twitter and/or liking on Facebook. In addition to pre-registration, players who purchased a Founder’s Pack can jump into Head Start starting October 1, which will allow them to join MapleStory 2 's vibrant and immersive world ahead of global launch on October 10. Along with beta improvements, Head Start (October 1 - October 10) will include: Character progression that carries over to the official launch 6 character slots Founder’s Pack items Access to Gemstones Lv. 1 - 50 Quest
First Engineering Faculty in Canada Named after a Woman: Business Leader Gina Cody Makes Historic $15 Million Donation to Montreal’s Concordia University24.9.2018 15:15 | Pressemelding
Three decades after becoming the first woman to earn a PhD in building engineering from Concordia University, Gina Parvaneh Cody, MEng 81, PhD 89, has made history by giving $15 million to her alma mater. In recognition of her transformative gift to the “Campaign for Concordia: Next-Gen. Now”, the university has named its faculty of engineering and computer science after the alumna. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20180924005425/en/ (Photo: Business Wire) The Gina Cody School of Engineering and Computer Science is the first engineering faculty in Canada — and one of the first internationally — to be named after a woman. Gina Cody, a top business leader and building engineer, credits much of her success to Concordia because the university provided her with an entrance scholarship. “I arrived in Canada as a young student from Iran in 1979 with $2,000,” she says. “Concordia welcomed me and provided me with support
Dole’s Standard Fruit Celebrates 20-Year Milestone as Environmental Leader24.9.2018 15:00 | Pressemelding
Earlier in September Dole Food Company participated in a celebration of the twentieth anniversary of the company’s initial receipt of its ISO 14001 Certification. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20180924005079/en/ Dole Fresh Fruit President Renato Acuña speaks at the anniversary celebration of Dole's landmark environmental sustainability certification. (Photo: Business Wire) On July 2, 1998, Standard Fruit Company of Costa Rica S.A., a subsidiary of Dole Food Company, Inc., became the first agricultural and banana company in the world to receive the globally recognized ISO 14001 Certification for its environmental management policy and the establishment of its Integrated Management System. With the certification, the company further strengthened its robust Environmental Management System, with results that place it at the forefront in the sustainable production of bananas and pineapples. The celebration event, h
Helsinki Joins New York in Commitment to Review Local Progress Toward Global Sustainable Development Goals24.9.2018 14:42 | Pressemelding
In July 2018, the City of New York became the first city in the world to submit to the United Nations its progress toward the Sustainable Development Goals (SDG’s) on city level. As the first European city Helsinki will follow New York City and become the second city in the world in effort to showcase crucial role of cities in achieving UN agenda for people, prosperity and planet. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20180924005633/en/ As the first European city Helsinki will follow New York City and become the second city in the world in effort to showcase crucial role of cities in achieving UN agenda for people, prosperity and planet. Photo: Jussi Hellsten The Mayor of Helsinki Jan Vapaavuori announced Helsinki’s commitment to the voluntary local review at a panel conversation with New York City’s Commissioner of International Affairs Penny Abeywardena at the Social Good Summit in New York City on Sunday. Even thou
ARTMS’ QUANTM Irradiation System™ to Be Featured at Two International Conferences in September24.9.2018 13:00 | Pressemelding
ARTMS Products, Inc. announced today that it has been invited to present at the National Nuclear Security Administration’s 2018 Mo-99 Topical Meeting on Tuesday, September 25th and the Third International Symposium on Technetium and other Radiometals in Chemistry and Medicine on Thursday, September 27th. Joel Kumlin will present at the 2018 Mo-99 Topical Meeting in Knoxville, TN, during Session 7, Production Projects and Technologies II, at 13:00EDT on September 25th. Mr. Kumlin will be discussing progress on implementation of the ARTMS QUANTM Irradiation System™ for producing technetium-99m. The QIS™ combines local production control and a cost-effective, easy-to-use solid target system for the production of Tc-99m on most cyclotron systems. ARTMS recently announced that the QIS™ received CE mark approval and has been installed in a number of countries throughout the world. ARTMS also announced that Dr. Paul Schaffer, CTO, has been invited to present at the Third International Symposi
Mavenir Wins 5G Asia “Best RAN Product” Award24.9.2018 13:00 | Pressemelding
Mavenir, focused on transforming mobile network economics for Communications Service Providers (CSPs), is proud to be awarded 5G Asia’s 2018 ‘Best RAN Product’ award for its innovative, flexible Cloud RAN solution. Mavenir’s Cloud RAN can save operators 37% in total cost of ownership (TCO) over a five-year period due to a 49% reduction in capex and a 31% annual reduction in opex1. The TechXLR8 5G Asia Awards were announced on September 19th in Singapore and celebrate excellence in the APAC’s technology and telecommunications community with the goal of showcasing the year’s greatest industry achievements. Mavenir’s Cloud RAN extends virtualization of the network to the edge and provides strategic differentiation by enabling the remote radio units (RRUs) to interwork with the virtualized cloud base band unit (vBBU) over ethernet fronthaul (FH) to the xRAN specification published early this year. Combined with network slicing support and flexibility for the vBBU to be co-located with the