European Commission Approves Cabometyx ® in Combination With Opdivo ® as a First-Line Treatment for Patients Living With Advanced Renal Cell Carcinoma

Regulatory News:

Ipsen (Euronext: IPN; ADR: IPSEY) today announced that the European Commission (EC) has approved Cabometyx^® (cabozantinib) in combination with Bristol Myers Squibb’s Opdivo^® (nivolumab) for the first-line treatment of advanced renal cell carcinoma (aRCC). This decision marks the first approval for Cabometyx in combination with another therapy in Europe and the third indication of Cabometyx in renal cell carcinoma (RCC).

“Today’s EC approval for the use of Cabometyx in combination with Opdivo^® provides an important new first-line treatment option for patients living with advanced renal cell carcinoma,” said Howard Mayer, Executive Vice President and Head of Research and Development, Ipsen. “At Ipsen, we’re proud that this, now approved, treatment option not only addresses key efficacy benefits, but also the need to maintain quality of life for patients. We look forward to collaborating with a broad range of European stakeholders to bring this unique combination to eligible patients living with advanced renal cell carcinoma.”

The EC approval is based on results from the pivotal Phase III CheckMate -9ER trial, presented during a Presidential Symposium at the European Society for Medical Oncology (ESMO) Virtual Congress 2020 and published in the New England Journal of Medicine (NEJM) on 3 March 2021. In the trial, Cabometyx in combination with Opdivo^® demonstrated significant improvements across all efficacy endpoints. In patients receiving the combination, median progression-free survival (PFS), the trial’s primary endpoint, was doubled compared to those receiving sunitinib alone: 16.6 months vs. 8.3 months respectively (HR: 0.51; 95% CI: 0.41–0.64; p<0.0001).1 Overall survival (OS) also demonstrated statistically significant improvements, reducing the risk of death by 40% versus sunitinib (HR: 0.60 [98.89% CI: 0.40-0.89]; p=0.001; median OS not reached in either arm).¹ In addition, Cabometyx in combination with Opdivo^® demonstrated a superior objective response rate (ORR), with twice as many patients responding compared to sunitinib (55.7% vs. 27.1%; p<0.0001) and 8.0% vs. 4.6% achieved a complete response respectively.¹ Key efficacy results were consistent across the pre-specified International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk and PD-L1 subgroups.¹ The combination was well tolerated and reflected the known safety profiles of the immunotherapy and tyrosine kinase inhibitor components in first-line aRCC.¹

Additional data from the CheckMate -9ER trial were also presented in February at the recent American Society of Clinical Oncology 2021 Genitourinary Cancers Symposium (ASCO GU). These data highlighted sustained superior efficacy of Cabometyx in combination with Opdivo^® versus sunitinib for the first-line treatment of aRCC with a median follow-up of 23.5 months, as well as data suggesting significantly improved health-related quality of life (HRQoL) outcomes for the combination versus sunitinib.^2,3 These HRQoL data, also included as part of the recently published NEJM publication, demonstrated that the combination was associated with a lower treatment burden, a decline in the risk of confirmed deterioration in HRQoL and a reduction of disease-related symptoms compared to sunitinib.^1,3

“The combination of nivolumab and cabozantinib pairs two proven agents for advanced renal cell carcinoma that together have shown superior efficacy across key endpoints and subgroups of patients compared to sunitinib in the CheckMate -9ER trial. Additionally, the combination’s safety profile was manageable with known protocols, leading to a low rate of treatment-related discontinuations,” said Marc- Oliver Grimm, M.D., Professor of Medicine and Urology Department Head, Jena University Hospital. “With today’s approval, clinicians in the EU will be able to offer patients with advanced renal cell carcinoma an additional combination therapy that may help them achieve early control of their disease and improve survival outcomes.”

This approval allows for the marketing of Cabometyx in combination with Opdivo^® in this indication in all 27 member states of the European Union, Norway, Liechtenstein and Iceland. The U.S. Food and Drug administration approved Cabometyx for patients with aRCC as a first-line treatment in combination with Opdivo^® in January 2021.

Ipsen thanks the patients and investigators involved in the CheckMate -9ER clinical trial.

About renal cell carcinoma
There are over 400,000 new cases of kidney cancer diagnosed worldwide each year.⁴ Of these, renal cell carcinoma (RCC) is the most common type of kidney cancer, accounting for approximately 90% of cases.^5,6 It is twice as common in men, and male patients account for over two thirds of deaths.⁴ If detected in the early stages, the five-year survival rate is high, but for patients with advanced or late- stage metastatic RCC the survival rate is much lower, around 12%, with no identified cure for this disease.^7,8

About the CheckMate -9ER trial
CheckMate -9ER is an open-label, randomized, multi-national Phase III trial evaluating patients with previously untreated advanced or metastatic RCC. A total of 651 patients (23% favorable risk, 58% intermediate risk, 20% poor risk; 25% PD-L1 ≥1%) were randomized to Cabometyx plus Opdivo^® (n= 323) versus sunitinib (n= 328). The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival (OS) and objective response rate (ORR). The primary efficacy analysis is comparing the doublet combination versus sunitinib in all randomized patients. The trial is sponsored by Bristol Myers Squibb and Ono Pharmaceutical Co and co-funded by Exelixis, Ipsen and Takeda Pharmaceutical Company Limited.

About Cabometyx (cabozantinib)
Cabometyx is currently approved in 57 countries, including in the European Union, the U.K., Norway, Iceland, Liechtenstein, 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 and Thailand for the treatment of advanced RCC in adults who have received prior VEGF-targeted therapy; in the European Union, the U.K., Liechtenstein, 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 and Thailand for previously untreated intermediate- or poor-risk advanced RCC; and in the European Union, the U.K., Liechtenstein, Norway, Iceland, Canada, Australia, 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 and Thailand for HCC in adults who have previously been treated with sorafenib.

The detailed recommendations for the use of Cabometyx^® are described in the Summary of Product Characteristics (SmPC) and in the U.S. Prescribing Information (PI).

Cabometyx is marketed by Exelixis, Inc. in the United States and by Takeda Pharmaceutical Company Limited in Japan. Ipsen has exclusive rights for the commercialization of Cabometyx outside of the U.S. and Japan. Cabometyx is a registered trademark of Exelixis, Inc.

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 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; 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.

Opdivo^® is a registered trademark of Bristol-Myers Squibb Company.

Ipsen—Cautionary Note Regarding Forward-Looking Statements
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References

1. Choueiri TK et al. Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl JMed. 2021; 384:829-841 DOI: 10.1056/NEJMoa2026982.
2. Motzer et al., ASCO-GU 2021. Nivolumab + cabozantinib (NIVO+CABO) vs sunitinib (SUN) as first-line therapy for advanced renal cell carcinoma (aRCC): extended follow-up and outcomes in the sarcomatoid subgroup of CheckMate -9ER.
3. Cella et al., ASCO-GU 2021. Patient-reported outcomes (PROs) of patients (pts) with advanced renal cell carcinoma (aRCC) treated with first-line (1L) nivolumab plus cabozantinib (NIVO+CABO) vs sunitinib (SUN): the randomized phase 3 CheckMate-9ER trial.
4. Kidney Cancer Factsheet. GLOBOCAN 2018. Accessed: March 2021. Available: https://gco.iarc.fr/today/data/factsheets/cancers/29-Kidney-fact-sheet.pdf.
5. Kidney Cancer. Mayo Clinic. Accessed: March 2021. Available: https://www.mayoclinic.org/diseases-conditions/kidney-cancer/symptoms-causes/syc-20352664.
6. Infographic: Kidney Cancer. Mayo Clinic. Accessed: March 2021. Available: https://www.mayoclinic.org/diseases-conditions/kidney-cancer/multimedia/kidney-cancer-infographic/ifg-20441505.
7. Survival rates for kidney cancer. American Cancer Society. Accessed: March 2021. Available: https://www.cancer.org/cancer/kidney-cancer/detection-diagnosis-staging/survival-rates.html.
8. Orlin, I et al. Renal cell carcinomas epidemiology in the era of widespread imaging. Journal of Clinical Oncology. 2019; 37:15. DOI: https://ascopubs.org/doi/10.1200/JCO.2019.37.15_suppl.e13083.

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