Ipsen provides update on CONTACT-02 Phase III trial in metastatic castration-resistant prostate cancer following final overall survival analysis

• Trial investigating Cabometyx^® (cabozantinib) in combination with atezolizumab demonstrated a positive trend towards improvement for one of the primary endpoints of overall survival, but did not meet statistical significance
• Ipsen will not pursue regulatory submissions for the combination regimen in countries where we have commercialization rights (outside of the US and Japan)
• We remain confident in the proven profile of Cabometyx as a monotherapy and in combination with immunotherapy, across approved and potential future indications

/EIN News/ -- PARIS, FRANCE, 15 September 2024 - Ipsen (Euronext: IPN; ADR: IPSEY) announced today detailed final overall survival (OS) data from the Phase III CONTACT-02 trial investigating the combination of Cabometyx^® (cabozantinib) and atezolizumab in metastatic castration-resistant prostate cancer (mCRPC). The trial investigated the combination regimen versus a second novel hormonal therapy (NHT) in men previously treated with one NHT and measurable soft-tissue disease. At a median follow-up of 24.0 months, these data demonstrated a numerical but not statistically significant improvement in OS for the combination versus a second NHT (hazard ratio: 0.89; 95% confidence interval: 0.72-1.10; P=0.296). As previously announced, the trial met the other primary endpoint of progression-free survival (PFS), demonstrating a statistically significant benefit in PFS.¹ Safety for the combination appeared to be consistent with the known safety profiles of the individual medicines, and no new safety signals were identified.

Based on the results of the final OS analysis and anticipated challenging regulatory environment in the countries in which Ipsen has commercialization rights (outside the US and Japan), Ipsen will not pursue regulatory submissions for this combination regimen in mCRPC.

We remain confident, in the proven profile of Cabometyx as a monotherapy and in combination with immunotherapy across approved indications, as well as its ongoing future potential.

Ipsen wishes to thank the patients, their families and healthcare teams for their participation in this clinical trial.

ENDS

About Cabometyx

Cabometyx (cabozantinib) is a small molecule that inhibits multiple receptor tyrosine kinases, including VEGFRs, MET, RET and the TAM family (TYRO3, MER, AXL).² These receptor tyrosine kinases are involved in both normal cellular function and pathologic processes such as oncogenesis, metastasis, tumor angiogenesis (the growth of new blood vessels that tumors need to grow), drug resistance, modulation of immune activities and maintenance of the tumor microenvironment.^2,3,4,5

Exelixis granted Ipsen exclusive rights for the commercialization and further clinical development of Cabometyx outside of the U.S. and Japan. Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited (Takeda) for the commercialization and further clinical development of Cabometyx for all future indications in Japan. Exelixis holds the exclusive rights to develop and commercialize Cabometyx in the U.S.

In over 65 countries outside of the United States and Japan, including in the European Union, Cabometyx is currently indicated as a:³

• Monotherapy for advanced renal cell carcinoma (aRCC).
  • as first-line treatment of adults with intermediate- or poor-risk disease.
  • in adults following prior VEGFR-targeted therapy.
• A combination with nivolumab for the first-line treatment of aRCC in adults.
• Monotherapy for the treatment of adults living with locally advanced or metastatic differentiated thyroid carcinoma, refractory or not eligible to radioactive iodine who have progressed during or after prior systemic therapy.
• Monotherapy for the treatment of hepatocellular carcinoma 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 (EU SmPC).

About mCRPC

Prostate cancer is the second most common cancer in men and the fourth most common cancer overall globally.⁶ In 2020, there were more than 1.4 million new cases of prostate cancer and about 375,300 deaths worldwide.⁶ Prostate cancer is considered mCRPC when it has spread beyond the prostate and does not respond to androgen-suppression therapies, a common treatment for prostate cancer.⁷ Men diagnosed with mCRPC often have a poor prognosis, with an estimated survival of 1-2 years.⁸

About CONTACT-02

CONTACT-02 is a global, multicenter, randomized, Phase III, open-label study that enrolled 575 patients who were randomized 1:1 to the experimental arm of Cabometyx in combination with atezolizumab and the control arm of a second NHT (either abiraterone and prednisone or enzalutamide). The study included patients with mCRPC who have measurable extra-pelvic soft tissue metastasis and who have progressed on one prior NHT. The two primary endpoints of the trial are progression-free survival (PFS) and OS. The PFS analysis was conducted in the first 400 randomized patients (PFS in the intent-to-treat [ITT] population) and assessed by a blinded independent radiology committee (BIRC) per RECIST 1.1. The OS analysis was conducted in the ITT population (n=507). The secondary endpoint is objective response rate (ORR) per BIRC. The trial is sponsored by Exelixis and co-funded by Ipsen, Roche and Takeda. Takeda is conducting the trial in Japan. More information about CONTACT-02 is available at ClinicalTrials.gov.

About Ipsen

We are a global biopharmaceutical company with a focus on bringing transformative medicines to patients in three therapeutic areas: Oncology, Rare Disease and Neuroscience.

Our pipeline is fueled by external innovation and supported by nearly 100 years of development experience and global hubs in the U.S., France and the U.K. Our teams in more than 40 countries and our partnerships around the world enable us to bring medicines to patients in more than 80 countries.

Ipsen is listed in Paris (Euronext: IPN) and in the U.S. through a Sponsored Level I American Depositary Receipt program (ADR: IPSEY). For more information, visit ipsen.com.

Ipsen contacts

Investors

• Craig Marks | +44 7584 349 193

Media

• Amy Wolf | +41 7 95 76 07 23
  
  
• Emma Roper | +44 7711 766 517

Disclaimers and/or Forward-Looking Statements

The forward-looking statements, objectives and targets contained herein are based on Ipsen’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 Ipsen’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 Ipsen’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 Ipsen. 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 medicine 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. Ipsen must face or might face competition from generic medicine 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 Ipsen may fail to achieve its objectives and be forced to abandon its efforts with regards to a medicine in which it has invested significant sums. Therefore, Ipsen cannot be certain that favorable results obtained during preclinical 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 medicine concerned. There can be no guarantees a medicine will receive the necessary regulatory approvals or that the medicine 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 healthcare legislation; global trends toward healthcare cost containment; technological advances, new medicine and patents attained by competitors; challenges inherent in new-medicine development, including obtaining regulatory approval; Ipsen’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 Ipsen’s patents and other protections for innovative medicines; and the exposure to litigation, including patent litigation, and/or regulatory actions. Ipsen also depends on third parties to develop and market some of its medicines which could potentially generate substantial royalties; these partners could behave in such ways which could cause damage to Ipsen’s activities and financial results. Ipsen 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 Ipsen’s partners could generate lower revenues than expected. Such situations could have a negative impact on Ipsen’s business, financial position or performance. Ipsen 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. Ipsen’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 Ipsen’s latest Universal Registration Document, available on ipsen.com.

References

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¹ Agarwal et al. Cabozantinib Plus Atezolizumab vs Second Novel Hormonal Therapy in Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC): Primary Analyses From the Phase 3 CONTACT-02 Study. As presented at the ASCO GU congress 2024, San Francisco, USA
² El-Khoueiry A. et al., Cabozantinib: An evolving therapy for hepatocellular carcinoma. Cancer Treatment Reviews. 2021 Jul;98:102221. DOI: 10.1016/j.ctrv.2021.102221.
³ European Medicines Agency. Cabometyx^® (cabozantinib) EU Summary of Product Characteristics. Available from: https://www.ema.europa.eu/en/documents/product-information/cabometyx-epar-product-information_en.pdf. Last accessed: September 2024
⁴ Yakes M. et al., Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth. Mol Cancer Ther. 2011;10:2298–2308. DOI: 10.1158/1535-7163.MCT-11-0264
⁵ Hsu et al., AXL and MET in Hepatocellular Carcinoma: A Systematic Literature Review. Liver Cancer 2021 DOI: 10.1159/000520501
⁶ Prostate cancer statistics. World Cancer Research Fund International. Available at: https://www.wcrf.org/cancer-trends/prostate-cancer-statistics/. Accessed August 2024
⁷ Prostate Cancer: Types of Treatment. Cancer.Net. Available at: https://www.cancer.net/cancer-types/prostate-cancer/types-treatment. Accessed September 2024
⁸ Moreira, D. M., et al. Predicting Time From Metastasis to Overall Survival in Castration-Resistant Prostate Cancer: Results From SEARCH. Clin Genitourin Cancer. 2017; 15: 60–66.e2

Attachment

• Ipsen PR_CONTACT-02 ESMO_15092024