Ipsen Announces CELESTIAL phase 3 Pivotal Trial Results in the New England Journal of Medicine
Ipsen (Euronext: IPN; ADR: IPSEY) today announced that The New England Journal of Medicine (NEJM) published results from the CELESTIAL phase 3 pivotal trial of cabozantinib in patients with previously treated advanced hepatocellular carcinoma (HCC).1 The data, originally presented at the 2018 American Society of Clinical Oncology’s Gastrointestinal Cancers Symposium (ASCO-GI) in January, demonstrate that cabozantinib provided a statistically significant and clinically meaningful improvement in overall survival (OS) versus placebo.
“Patients with this form of advanced liver cancer have very limited treatment options once their disease progresses following treatment with sorafenib,” said Ghassan K. Abou-Alfa, M.D., Memorial Sloan Kettering Cancer Center, New York and lead investigator on CELESTIAL. “These results suggest that, if approved, cabozantinib could become an important addition to the treatment landscape that may help slow disease progression and, critically, improve survival for these patients.”
“Patients with advanced HCC have a very poor prognosis and limited treatment options. Given the worldwide prevalence of advanced HCC, there is a continued urgency to bring new treatment options to these patients”, added Lorenza Rimassa M.D., Deputy Director, Medical Oncology Unit, Humanitas Cancer Center Humanitas Research Hospital, Milan. ”The clinically significant benefits in both overall survival and progression-free survival shown in the CELESTIAL trial, in patients previously treated with up to two treatment lines, suggest that cabozantinib could become (when approved) an important addition to the treatment landscape for this patient population.”
Ipsen received validation by the European Medicines Agency in March 2018 for its application for variation to the Cabometyx® marketing authorization to include the new indication for patients with previously treated advanced HCC. Ipsen’s partner Exelixis announced in May 2018 that the U.S. Food and Drug Administration (FDA) accepted the company’s supplemental New Drug Application (sNDA) for Cabometyx® (cabozantinib) tablets as a treatment for patients with previously treated HCC. The filing has been assigned a Prescription Drug User Fee Act action date of January 14, 2019.
“This publication of CELESTIAL phase 3 data in the NEJM this week further validates the medical importance of these results for the treatment of patients with advanced liver cancer” said Alexandre Lebeaut, Executive Vice President Research & Development, Chief Scientific Officer, Ipsen. “Together with our partner Exelixis we relentlessly contribute to expanding the clinical benefits of cabozantinib across solid tumors to address unmet medical needs”.
Median OS in CELESTIAL was 10.2 months with cabozantinib versus 8.0 months with placebo (HR 0.76, 95 percent CI 0.63-0.92; p=0.0049). Median progression-free survival (PFS) was more than doubled, at 5.2 months with cabozantinib and 1.9 months with placebo (HR 0.44, 95 percent CI 0.36-0.52; p<0.0001). Objective response rates per RECIST 1.1 were 4 percent with cabozantinib and 0.4 percent with placebo (p=0.0086). Disease control (partial response or stable disease) was achieved by 64 percent of patients in the cabozantinib group compared with 33 percent of patients in the placebo group.
In a subgroup analysis of patients whose only prior therapy for advanced HCC was sorafenib (70 percent of patients in the study), median OS was 11.3 months with cabozantinib versus 7.2 months with placebo (HR 0.70, 95 percent CI 0.55-0.88). Median PFS in the subgroup was 5.5 months with cabozantinib versus 1.9 months with placebo (HR 0.40, 95 percent CI 0.32-0.50).
Adverse events were consistent with the known safety profile of cabozantinib. The most common (≥10 percent) grade 3 or 4 adverse events in the cabozantinib group compared to the placebo group were palmar-plantar erythrodysesthesia (17 percent vs. 0 percent), hypertension (16 percent vs. 2 percent), increased aspartate aminotransferase (12 percent vs. 7 percent), fatigue (10 percent vs. 4 percent) and diarrhea (10 percent vs. 2 percent). Treatment-related grade 5 adverse events occurred in six patients in the cabozantinib group (hepatic failure, esophagobronchial fistula, portal vein thrombosis, upper gastrointestinal hemorrhage, pulmonary embolism and hepatorenal syndrome) and in one patient in the placebo group (hepatic failure). Sixteen percent of patients in the cabozantinib arm and three percent of patients in the placebo arm discontinued treatment due to treatment-related adverse events.
CELESTIAL is a randomized, double-blind, placebo-controlled global phase 3 study of cabozantinib versus placebo in patients with advanced hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. The study was conducted at more than 100 sites globally in 19 countries. The trial was designed to enroll 760 patients with advanced hepatocellular carcinoma (HCC) who previously received sorafenib and may have received up to two prior systemic cancer therapies for hepatocellular carcinoma (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 hepatocellular carcinoma (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.
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 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. The safety data in the study were consistent with the established profile of cabozantinib.
Hepatocellular carcinoma (HCC) is the most common form of liver cancer in adults.2 The disease originates in cells called hepatocytes found in the liver. With approximately 800’000 new cases diagnosed each year, hepatocellular carcinoma (HCC) is the sixth most common cancer and the second-leading cause of cancer deaths worldwide.3,4 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 2020.5 Without treatment, patients with the disease in advanced stage usually survive between 4 and 8 months.6
About CABOMETYX ® (cabozantinib)
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 renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy and on September 9, 2016, the European Commission approved Cabometyx® tablets for the treatment of advanced renal cell carcinoma (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.
On December 19, 2017, Exelixis received approval from the FDA for Cabometyx® for the expanded indication of treatment of first-line advanced RCC .
On May 17, 2018, Ipsen announced that the European Commission approved Cabometyx® for the first-line treatment of adults with intermediate- or poor- risk advanced renal cell carcinomain the European Union, Norway and Iceland.
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, Neuroscience 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 over €1.9 billion in 2017, 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 located in the heart of the leading biotechnological and life sciences hubs (Paris-Saclay, France; Oxford, UK; Cambridge, US). The Group has about 5,400 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. Abou-Alfa, G, Meyer T, Cheng AL, et al. Cabozantinib in patients with
advanced and progressinig hepatocellular carcinoma. N Engl J Med. 2018.
2. McGlynn KA, London WT. The Global Epidemiology of Hepatocellular Carcinoma, Present and Future. Clinics in liver disease. 2011;15(2):223-x. doi:10.1016/j.cld.2011.03.006.
3. 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
4. GLOBOCAN International Agency for Research on Cancer (IARC). Available at: http://gco.iarc.fr/today/fact-sheets-cancers?cancer=7&type=0&sex=0
5. GLOBOCAN International Agency for Research on Cancer (IARC). Available at: http://globocan.iarc.fr/Pages/burden_sel.aspx
6. Annals of Oncology 23 (Supplement 7): vii41–vii48, 2012
Ian Weatherhead, +44 (0) 1753 627733
Vice President, Corporate External Communications
Brigitte Le Guennec, +33 (0)1 58 33 51 17
Senior Manager, Global External Communications
Eugenia Litz, +44 (0) 1753 627721
Vice President, Investor Relations
Myriam Koutchinsky, +33 (0)1 58 33 51 04
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
AURAK Enters into a Memorandum of Understanding with Al-Farabi Kazakh National University22.7.2018 09:52 | Pressemelding
The American University of Ras Al Khaimah (AURAK) President, Professor Hassan Hamdan Al Alkim, and the Al-Farabi Kazakh National University (KazNU) Rector, Professor Galimkair Mutanov, of the Republic of Kazakhstan, signed a Memorandum of Understanding (MoU), agreeing to exchange students, faculty, and research. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20180722005025/en/ The Al-Farabi Kazakh National University (KazNU) Rector, Professor Galimkair Mutanov, of the Republic of Kazakhstan and the American University of Ras Al Khaimah (AURAK) President, Professor Hassan Hamdan Al Alkim, exchange a gift to commemorate their universities uniting in an MoU agreement. (Photo: AETOSWire) In the spirit of fostering a close international relationship between the Republic of Kazakhstan and the United Arab Emirates, developing bilateral relations in educational and scientific fields, and wishing to make their own contributions to the
Philip Morris International Announces Non-Executive Board Chairman Louis Camilleri to Assume CEO Role at Ferrari S.p.A.21.7.2018 18:19 | Pressemelding
The board of directors of Philip Morris International (NYSE:PM) has its board member, Sergio Marchionne, and his family in our thoughts and prayers during this challenging time. We congratulate our board chairman, Louis Camilleri, as he assumes the role of CEO of Ferrari S.p.A. The long term relationship between our two companies is deep and meaningful and we look forward to continued business collaboration. Mr. Camilleri will continue to serve as non-executive chairman of the PMI board. Philip Morris International: Who We Are We are a leading international tobacco company engaged in the manufacture and sale of cigarettes and other nicotine-containing products in markets outside the United States of America. We’re building our future on smoke-free products. Through multidisciplinary capabilities in product development, state-of-the-art facilities and scientific substantiation, we aim to ensure that our smoke-free products meet adult consumer preferences and rigorous regulatory requirem
Loxam Announces a Conditional Agreement to Acquire UK Platforms20.7.2018 14:51 | Pressemelding
Loxam Group (“Loxam”) announces that its wholly-owned subsidiary Nationwide Platforms Limited (“Nationwide”) has entered into a conditional agreement with HSS Hire Group plc (“HSS”) with respect to the acquisition of UK Platforms Limited (“UKP”). UKP specializes in renting powered access equipment from its 12 branches located throughout the United Kingdom. The company has approximately 130 employees and operates a fleet of 3,000 units. UKP is controlled by HSS since 2013. As part of this transaction, Nationwide has entered into a commercial agreement with HSS to provide powered access equipment to complement HSS’ existing fleet. The closing of the transaction is subject to the approval by HSS’ shareholders and the confirmation that it will not be referred to the Competition and Mergers Authority. The transaction is expected to close before year end 2018. Don Kenny, CEO of Loxam’s Powered Access Division states: “I am delighted with the acquisition of UKP which will further reinforce NW
Schlumberger Announces Second-Quarter 2018 Results20.7.2018 11:00 | Pressemelding
Schlumberger Limited (NYSE: SLB) today reported results for the second quarter of 2018. (Stated in millions, except per share amounts) Three Months Ended Change Jun. 30, 2018 Mar. 31, 2018 Jun. 30, 2017 Sequential Year-on-year Revenue $8,303 $7,829 $7,462 6% 11% Pretax operating income $1,094 $974 $950 12% 15% Pretax operating margin 13.2% 12.4% 12.7% 75 bps 45 bps Net income - GAAP basis $430 $525 $(74) -18% n/m Net income, excluding charges & credits* $594 $525 $488 13% 22% Diluted EPS - GAAP basis $0.31 $0.38 $(0.05) -18% n/m Diluted EPS, excluding charges & credits* $0.43 $0.38 $0.35 13% 23% *These are non-GAAP financial measures. See section below entitled "Charges & Credits" for details. n/m = not meaningful Schlumberger Chairman and CEO Paal Kibsgaard commented, “The second quarter was both busy and exciting for Schlumberger as we completed a number of major milestones in preparation for the broad-based global activity upturn that is now emerging. We delivered solid top-line gro
H.I.G. Capital Announces the Sale of KidsFoundation19.7.2018 19:50 | Pressemelding
H.I.G. Capital (“H.I.G.”), a leading global private equity investment firm with more than €21 billion of equity capital under management, announced today that one of its affiliates has entered a definitive agreement to sell the KidsFoundation Group (“KidsFoundation”), the Dutch market leader in childcare services, to Onex Corporation (“Onex”)(TSX:ONEX). Terms were not disclosed. Headquartered in Almere, the Netherlands, KidsFoundation provides high-quality childcare to nearly 30,000 children between the ages of six weeks and 12 years. H.I.G. created KidsFoundation in 2014 through the acquisition of assets from the estate of Estro Group. During H.I.G.’s ownership, the company has developed strongly with significant capital invested by H.I.G. to create a high-quality childcare offering. H.I.G. worked with KidsFoundation management to optimise the footprint of the company by exiting loss-making locations, introduce new IT systems to drive operational improvement and develop an internal M&
SIG Combibloc Group Holdings S.à r.l.: 2018 Second Quarter Results19.7.2018 16:01 | Pressemelding
We are pleased to announce our quarterly conference call to discuss the results of SIG Combibloc Group Holdings S.à r.l. for the second quarter ended June 30, 2018. Date: Monday, July 23, 2018 Time: 15.00 CEST / 14.00 BST / 9.00 EDT The call information will be distributed on our secure site. If you would like access to our call, please contact firstname.lastname@example.org . Regards, SIG Combibloc Group Holdings S.à r.l. View source version on businesswire.com: https://www.businesswire.com/news/home/20180719005634/en/ Contact information SIG Combibloc Group Holdings S.à r.l. Jennifer Gough email@example.com