ALAMEDA, CA, USA & PARIS, France I June 28, 2021 IExelixis, Inc. (NASDAQ: EXEL) and Ipsen (Euronext: IPN; ADR: IPSEY) today announced that COSMIC-312, the ongoing phase 3 pivotal trial evaluating cabozantinib (CABOMETYX®) in combination with atezolizumab versus sorafenib in patients with previously untreated advanced hepatocellular carcinoma (HCC), met one of the primary endpoints, demonstrating significant improvement in progression-free survival (PFS) at the planned primary analysis. A prespecified interim analysis for the second primary endpoint of overall survival (OS), conducted at the same time as the primary analysis for PFS, showed a trend favoring the combination of cabozantinib and atezolizumab but did not reach statistical significance. Based on the preliminary OS data, Exelixis anticipates that the probability of reaching statistical significance at the time of the final analysis is low. The trial will continue as planned to the final analysis of OS; results are anticipated in early 2022.

In the analysis of the primary endpoint of PFS in the PFS intent-to-treat population, cabozantinib in combination with atezolizumab significantly reduced the risk of disease progression or death by 37% compared with sorafenib (hazard ratio: 0.63; 99% confidence interval: 0.44-0.91; P=0.0012). Safety for the combination appeared to be consistent with the known safety profiles of the individual medicines, and no new safety signals were identified. Exelixis plans to discuss the trial results and next steps for a potential regulatory filing with the U.S. Food and Drug Administration (FDA).

“While we are encouraged by the data supporting the potential for the combination of cabozantinib and atezolizumab to reduce the risk of disease progression or death, we are disappointed by the interim result of lack of significant improvement on overall survival versus the comparator arm,” said Michael M. Morrissey, Ph.D., Exelixis’ President and Chief Executive Officer. “As these data continue to mature, we are working to understand the potential impact of various contributing factors on the results, including patient demographics, subsequent anti-cancer therapy and the impact of COVID-19 on the trial. We anticipate presenting the results at a future medical conference.”

About COSMIC-312

COSMIC-312 is a global, multicenter, randomized, controlled phase 3 pivotal trial that aimed to enroll approximately 840 patients at up to 200 sites globally. Patients were randomized approximately 2:1:1 to one of three arms: cabozantinib (40 mg) in combination with atezolizumab, sorafenib, or cabozantinib (60 mg). Exelixis is sponsoring COSMIC-312, and Ipsen is co-funding the trial. Genentech, a member of the Roche Group, is providing atezolizumab for use in this trial. More information about COSMIC-312 is available at ClinicalTrials.gov.

About HCC

More than 900,000 new cases of liver cancer, 90% of which are HCC, are diagnosed worldwide each year.1,2 HCC is a leading cause of cancer-related death, expected to cause 1 million global deaths annually by 2030.3 In the U.S., HCC is the fastest-rising cause of cancer-related death.4 Median survival for patients with symptomatic advanced HCC who are treated with systemic therapies is just 1 to 1.5 years.2

About CABOMETYX® (cabozantinib)

In the U.S., CABOMETYX tablets are approved for the treatment of patients with advanced renal cell carcinoma (RCC); for the treatment of patients with HCC who have been previously treated with sorafenib; and for patients with advanced RCC as a first-line treatment in combination with nivolumab. Outside of the U.S., CABOMETYX is approved in 58 countries, including in the European Union, the U.K., Norway, Iceland, Australia, New Zealand, Switzerland, South Korea, Canada, Brazil, Taiwan, Hong Kong, Singapore, Macau, Jordan, Lebanon, Russian Federation, Ukraine, Turkey, United Arab Emirates, Saudi Arabia, Serbia, Israel, Mexico, Chile, Peru, Panama, Guatemala, Dominican Republic, Ecuador, Thailand and Malaysia for the treatment of advanced RCC in adults who have received prior VEGF-targeted therapy; in the European Union, the U.K., Norway, Iceland, Canada, Australia, Brazil, Taiwan, Hong Kong, Singapore, Lebanon, Jordan, Russian Federation, Ukraine, Turkey, United Arab Emirates, Saudi Arabia, Israel, Mexico, Chile, Peru, Panama, Guatemala, Dominican Republic, Ecuador, Thailand and Malaysia for previously untreated intermediate- or poor-risk advanced RCC; and in the European Union, the U.K., Norway, Iceland, Canada, Australia, New Zealand, Switzerland, Saudi Arabia, Serbia, Israel, Taiwan, Hong Kong, South Korea, Singapore, Jordan, Russian Federation, Ukraine, Turkey, Lebanon, United Arab Emirates, Peru, Panama, Guatemala, Chile, Dominican Republic, Ecuador, Thailand and Malaysia for HCC in adults who have previously been treated with sorafenib. In the European Union, CABOMETYX is also approved in combination with nivolumab as first line treatment for patients living with advanced RCC. In 2016, Exelixis granted Ipsen exclusive rights for the commercialization and further clinical development of cabozantinib outside of the United States and Japan. In 2017, Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited for the commercialization and further clinical development of cabozantinib for all future indications in Japan. Exelixis holds the exclusive rights to develop and commercialize cabozantinib in the United States.

CABOMETYX is not indicated as a treatment for previously untreated advanced HCC.

EUROPEAN UNION IMPORTANT SAFETY INFORMATION

For detailed recommendations on the use of CABOMETYX in the European Union, please see the Summary of Product Characteristics.

About Exelixis

Founded in 1994, Exelixis, Inc. (Nasdaq: EXEL) is a commercially successful, oncology-focused biotechnology company that strives to accelerate the discovery, development and commercialization of new medicines for difficult-to-treat cancers. Following early work in model system genetics, we established a broad drug discovery and development platform that has served as the foundation for our continued efforts to bring new cancer therapies to patients in need. Our discovery efforts have resulted in four commercially available products, CABOMETYX® (cabozantinib), COMETRIQ® (cabozantinib), COTELLIC® (cobimetinib) and MINNEBRO® (esaxerenone), and we have entered into partnerships with leading pharmaceutical companies to bring these important medicines to patients worldwide. Supported by revenues from our marketed products and collaborations, we are committed to prudently reinvesting in our business to maximize the potential of our pipeline. We are supplementing our existing therapeutic assets with targeted business development activities and internal drug discovery – all to deliver the next generation of Exelixis medicines and help patients recover stronger and live longer. Exelixis is a member of the Standard & Poor’s (S&P) MidCap 400 index, which measures the performance of profitable mid-sized companies. In November 2020, the company was named to Fortune’s 100 Fastest-Growing Companies list for the first time, ranking 17th overall and the third-highest biopharmaceutical company. For more information about Exelixis, please visit www.exelixis.com, follow @ExelixisInc on Twitter or like Exelixis, Inc. on Facebook.

About Ipsen

Ipsen is a global mid-size biopharmaceutical company with a focus on transformative medicines in Oncology, Rare Disease and Neuroscience. Ipsen also has a well-established Consumer Healthcare business. With total sales over €2.5 billion in 2020, Ipsen sells more than 20 drugs in over 110 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; Shanghai, China). The Group has about 5,700 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.

1 International Agency for Research on Cancer. GLOBOCAN 2020. Liver Fact Sheet. Available at: http://gco.iarc.fr/today/data/factsheets/cancers/11-Liver-fact-sheet.pdf. Accessed June 2021.
2 Llovet, J.M., Kelley, R.K., Villanueva, A. et al. Hepatocellular carcinoma. Nat Rev Dis Primers. 2021;7(1):6.
3 Kim, E., Viatour, P. Hepatocellular carcinoma: old friends and new tricks. Exp Mol Med. 2020;52:1898–1907.
4 Rawla, P., Sunkara, T., Muralidharan, P., et al. Update in global trends and aetiology of hepatocellular carcinoma. Contemporary oncology (Pozn). 2018;22(3):141–150.

SOURCE: Exelixis