U.K. MHRA grants marketing authorisation for Cabozantinib Ipsen® – a first for previously treated advanced neuroendocrine tumours

• Cabozantinib Ipsen^® (cabozantinib) is the first and only systemic therapy approved in the U.K. for previously treated unresectable or metastatic neuroendocrine tumours (NETs) – regardless of tumour site or previous non-somatostatin analogue-based (SSA-based) systemic therapy¹
• Approval based on pivotal CABINET Phase III trial which demonstrated a 77% and 62% reduction in the risk of disease progression or death versus placebo for pancreatic NETs (pNETs) and extra-pancreatic NETs (epNETs) respectively – the median progression-free survival (PFS) for cabozantinib was 13.8 months versus 4.4 months for placebo in the advanced pNETs cohort, while the PFS was 8.4 months for cabozantinib versus 3.9 for placebo in the epNETs cohort²
• NETs is estimated to affect at least 20,000 people in the U.K.³ and the global prevalence is estimated to be rising⁴

LONDON, U.K., 22 SEPTEMBER 2025 – Ipsen (Euronext: IPN; ADR: IPSEY) announced today that the U.K. Medicines and Healthcare products Regulatory Agency (MHRA) has granted marketing authorisation for cabozantinib in adult patients with unresectable or metastatic, well differentiated pNETs and epNETs who have progressed following at least one prior systemic therapy other than SSAs.¹

NETs affects approximately 35 per 100,000 people in England.⁵ The number of people newly diagnosed with NETs globally is believed to be rising with a higher estimated prevalence than pancreatic or bladder cancer.^5-7

Most forms of NETs develop slowly, can originate in various parts of the body⁸ and require multiple lines of therapy as the disease progresses.^9,10 Treatment options upon progression are often limited depending on primary tumour site and other factors, making it challenging to define optimal sequencing of treatments specific to individual patient needs.^10,11 For over 20% of NETs patients diagnosed with lung NETs,¹² there have been no approved treatment options upon progression on a prior therapy.

“Neuroendocrine cancers can have a huge impact on the lives of those affected, particularly as most cases are diagnosed at an advanced stage”, commented Catherine Bouvier-Ellis, CEO and Co-Founder of Neuroendocrine Cancer UK. “The authorisation of a new treatment option for this complex form of cancer offers some hope for patients to maintain their quality of life while limiting disease progression. This is especially important for a cancer in which few to no other options currently exist.”

The MHRA decision was based on data from the Phase III CABINET trial which investigated cabozantinib versus placebo in people living with advanced pNETs or epNETs whose disease had progressed after prior systemic therapy, excluding SSA-based systemic therapies. Trial results, as presented at the 2024 European Society for Medical Oncology Congress and simultaneously published in the New England Journal of Medicine, demonstrated a 77% and 62% reduction in the risk of disease progression or death versus placebo in advanced pNETs and epNETs respectively (p<0.001).²

At a median follow-up of 13.8 months in the pNET-cohort, median PFS was 13.8 months for cabozantinib versus 4.4 months for placebo (hazard ratio (HR) 0.23 [95% confidence interval (CI) 0.12-0.42] p<0.001). In the epNET cohort, at a median follow-up of 10.2 months, median PFS was 8.4 months for cabozantinib versus 3.9 months for placebo (HR 0.38 [95% CI 0.25-0.59] p<0.001).² Health-related quality of life was also found to be maintained with cabozantinib versus placebo.¹³

The safety profile of cabozantinib observed in each cohort was consistent with its known safety profile and no new safety signals were identified. Grade 3 or higher adverse events were noted in 62 ̶ 65% of the patients treated with cabozantinib, as compared with 23 ̶ 27% of the patients who received placebo. Common treatment-related adverse events of grade 3 or higher included hypertension, fatigue, diarrhoea, and thromboembolic events.²

“This U.K. marketing authorisation marks a critical milestone in making a licensed and efficacious treatment option available to patients upon progression. We are actively engaging with the National Institute for Health and Care Excellence (NICE) to ensure that individuals living with this often overlooked form of cancer in the U.K. have timely access to this approved therapeutic option,” said Dr Ian Gray, U.K. & Ireland Interim Medical Director at Ipsen.

Cabozantinib has been submitted for review by NICE, with a decision expected later in 2025. Cabozantinib was granted marketing authorisation by the European Medicines Agency (EMA) for advanced NETS in July following a positive opinion from the Committee for Medicinal Products for Human Use in June.

About Cabozantinib Ipsen^® (cabozantinib)¹

The detailed recommendations for the use of cabozantinib are described in the Summary of Product Characteristics (SmPC) from the MHRA.

Exelixis granted Ipsen exclusive rights for the commercialisation and further clinical development of cabozantinib outside of the U.S. and Japan.

In over 65 countries outside of the United States and Japan, including in the European Union, cabozantinib also has indications in advanced renal cell carcinoma, locally advanced or metastatic differentiated thyroid carcinoma and hepatocellular carcinoma.

About the Phase III CABINET trial²

The multicentre Phase III CABINET pivotal trial (randomised, double-blinded phase III trial of CABozantinib versus placebo In patients with advanced NEuroendocrine Tumours after progression on prior therapy) enrolled 298 patients in the U.S. at the time of the analysis.

Patients were randomised 2:1 to cabozantinib or placebo in two separately powered cohorts. The epNET cohort included patients with the following primary tumour sites: gastrointestinal tract, lung, thymus, unknown primary and other organs. Each cohort was randomised separately and had its own statistical analysis plan. Patients must have had measurable disease per RECIST 1.1 criteria and must have experienced disease progression or intolerance after at least one U.S. Food and Drug Administration-approved line of prior systemic therapy other than SSAs. The primary endpoint in each cohort was PFS per RECIST 1.1 by retrospective blinded independent central review, or death from any cause. Upon confirmation of disease progression, patients were unblinded, and those receiving placebo were permitted to cross over to open-label therapy with cabozantinib. Secondary endpoints included overall survival, objective response rate and safety. More information about this trial 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 fuelled 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 100 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

Media (Local)
Sam Howland sam.howland@ipsen.com
Ed Kos ed.kos@envisionpharma.com
Christina Halm christina.halm@envisionpharma.com

CBZ-UK-000799 | September 2025

Disclaimers and/or forward-looking statements

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References

1. Summary of Product Characteristics. Cabometyx. Available upon request.
2. Chan JA et al. Phase 3 Trial of Cabozantinib to Treat Advanced Neuroendocrine Tumors. New England Journal of Medicine. 2024; 392 (7): 653-665.
3. Genus T et al. Incidence and prevalence of neuroendocrine tumours in England. Endocrine Abstracts (2017) 52 OC3.
4. Singh S et al Patient-Reported Burden of a Neuroendocrine Tumor (NET) Diagnosis: Results From the First Global Survey of Patients With NETs. J Glob Oncol. 2017 Feb; 3(1): 43–53.
5. Öberg K, Castellano, D. Current knowledge on diagnosis and staging of neuroendocrine tumors. Cancer Metastasis Rev 30 (Suppl 1), 3–7 (2011).
6. Durma AD et al. Epidemiology of Neuroendocrine Neoplasms and Results of Their Treatment with [¹⁷⁷Lu]Lu-DOTA-TATE or [¹⁷⁷Lu]Lu-DOTA-TATE and [⁹⁰Y]Y-DOTA-TATE—A Six-Year Experience in High-Reference Polish Neuroendocrine Neoplasm Center. Cancers 2023, 15(22), 5466.
7. Globocan: International Agency for Research on Cancer – Cancer Today. https://gco.iarc.who.int/media/globocan/factsheets/populations/900-world-fact-sheet.pdf. Accessed September 2025.
8. National Cancer Institute. Neuroendocrine tumor (NET). Available at: https://www.cancer.gov/pediatric-adult-rare-tumor/rare-tumors/rare-endocrine-tumor/carcinoid-tumor. Accessed September 2025.
9. Pavel M et al. Gastroenteropancreatic neuroendocrine neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020;31(7):844-860.
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12. White BE et al. (2022) Incidence and survival of neuroendocrine neoplasia in England 1995–2018: A retrospective, population-based study. The Lancet Regional Health – Europe 2022;23:100510.
13. Dueck AC et al. Health-related quality of life (HRQoL) in the phase 3 trial of cabozantinib vs placebo for advanced neuroendocrine tumors (NET) after progression on prior therapy (CABINET, Alliance A021602). As presented at ASCO Congress 2025.