AstraZeneca PLC - Enhertu approved in the EU for breast cancer
Enhertu approved in the EU for the treatment
of HER2-positive metastatic breast cancer
Approval based on DESTINY-Breast01 Phase II trial which showed clinically meaningful and durable responses in patients with previously treated disease
AstraZeneca and Daiichi Sankyo Company, Limited (Daiichi Sankyo)'s Enhertu (trastuzumab deruxtecan) has been granted conditional approval in the European Union (EU) as a monotherapy for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens.
The approval by the European Commission was based on positive results from the single-arm DESTINY-Breast01 Phase II trial, in which Enhertu showed clinically meaningful and durable antitumour activity in patients with HER2-positive metastatic breast cancer who had received two or more prior anti-HER2-based regimens.4 It follows the
In the DESTINY-Breast01 Phase II trial, after a median follow-up of 20.5 months, Enhertu showed a confirmed objective response rate (ORR) of 61.4%, including a 6.5% complete response rate and a 54.9% partial response rate, and an estimated median duration of response (DoR) of 20.8 months for patients with HER2-positive metastatic breast cancer who had received at least two previous lines of therapy.4
The analysis was presented during the 2020 San Antonio Breast Cancer Symposium. An earlier analysis with a median follow-up of 11.1 months was published in The New England Journal of Medicine in
The safety of Enhertu has been evaluated in a pooled analysis of 234 patients with unresectable or metastatic HER2-positive breast cancer who received at least one dose of Enhertu 5.4mg/kg in clinical trials. The most common adverse reactions were nausea, fatigue, vomiting, alopecia, constipation, decreased appetite, anaemia, neutropenia, diarrhoea, thrombocytopenia, cough, leukopenia and headache. Cases of interstitial lung disease (ILD) or pneumonitis, were reported in 15.0% of patients, and in 2.6% of patients, ILD led to death.
Enhertu (5.4mg/kg) is approved in the US under accelerated approval, and in
Enhertu is being further assessed in several ongoing Phase III breast cancer trials as part of a broad development programme, including DESTINY-Breast02, a confirmatory trial in 3rd-line HER2-positive metastatic breast cancer, and DESTINY-Breast03, as a 2nd-line treatment. DESTINY-Breast04 is testing Enhertu in patients with metastatic breast cancer and low expression of HER2; and DESTINY-Breast05 is evaluating Enhertu as an adjuvant treatment of patients with high-risk HER2-positive early breast cancer. Additional ongoing trials are testing Enhertu in combination with other anti-cancer medicines in HER2-positive and HER2-low metastatic breast cancer.
Following EU approval, an amount of
Sales of Enhertu in most EU territories are recognised by Daiichi Sankyo. AstraZeneca reports its share of gross profit margin from Enhertu sales in those territories as collaboration revenue in the Company's financial statements. AstraZeneca will record product sales in respect of sales made in territories where AstraZeneca is the selling party.
For further details on the financial arrangements, please consult the collaboration agreement from
HER2-positive breast cancer
HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours, including breast cancer. HER2 overexpression may be associated with a specific HER2 gene alteration known as HER2 amplification and is often associated with aggressive disease and a poor prognosis in breast cancer.6
There remain significant unmet clinical needs for patients with HER2-positive metastatic breast cancer. The disease remains incurable with patients eventually progressing after currently available treatment options.7,8
DESTINY-Breast01 was a single-arm, open-label, global, multicentre, two-part Phase II trial testing the safety and efficacy of Enhertu in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab emtansine. The primary endpoint of the trial was ORR, as determined by independent central review. Secondary objectives included DoR, disease control rate, clinical benefit rate, progression-free survival and overall survival.
Enhertu (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the US) is a HER2-directed antibody drug conjugate (ADC). It is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca's ADC scientific platform.
ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy ('payload') to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. Enhertu is comprised of a humanised anti-HER2 IgG1 monoclonal antibody with the same amino acid sequence as trastuzumab attached to a topoisomerase I inhibitor payload, an exatecan derivative, via by a tetrapeptide-based cleavable linker.
A comprehensive development programme is underway globally, with nine registrational trials evaluating the efficacy and safety of Enhertu monotherapy across multiple HER2 cancers, including breast, gastric and lung cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.
Daiichi Sankyo collaboration
Daiichi Sankyo and AstraZeneca entered a global collaboration to jointly develop and commercialise Enhertu (a HER2-directed ADC) in
AstraZeneca in breast cancer
Driven by a growing understanding of breast cancer biology, AstraZeneca is starting to challenge, and redefine, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need - with the bold ambition to one day eliminate breast cancer as a cause of death.
AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumour environment. AstraZeneca aims to continue to transform outcomes for HR-positive breast cancer with foundational medicines Faslodex (fulvestrant) and Zoladex (goserelin) and the next-generation SERD and potential new medicine AZD9833. PARP inhibitor, Lynparza (olaparib) is a targeted treatment option for metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with MSD (Merck & Co., Inc. in the US and
Building on the first approval of Enhertu, a HER2-directed ADC, in previously treated HER2-positive metastatic breast cancer, AstraZeneca and Daiichi Sankyo are exploring its potential in earlier lines of treatment and in new breast cancer settings. To bring much needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is testing immunotherapy durvalumab in combination with other oncology medicines, including Lynparza and Enhertu, assessing the potential of AKT kinase inhibitor, capivasertib, in combination with chemotherapy, and collaborating with Daiichi Sankyo to explore the potential of TROP2-directed ADC, datopotamab deruxtecan.
AstraZeneca in oncology
AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients' lives and the Company's future. With seven new medicines launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers.
By harnessing the power of six scientific platforms - Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response, Antibody Drug Conjugates, Epigenetics, and Cell Therapies - and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and, one day, eliminate cancer as a cause of death.
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in
1. GLOBOCAN 2020 Breast Cancer Fact Sheet. World Health Organization. Accessed
2. DeKoven M, et al. Treatment pattern by hormone receptors and HER2 status in patients with metastatic breast cancer in the
3. Sledge G, et al. Past, Present, and Future Challenges in Breast Cancer Treatment. J Clin Oncol. 2014;32(19):1979-1986.
4. European Medicines Agency. Enhertu summary of product characteristics. Accessed
5. Modi, S et al. Trastuzumab deruxtecan in previously treated HER2-positive breast cancer. N Engl J Med. 2020;382:610-621; DOI: 10.1056/NEJMoa1914510.
6. Iqbal N, et al. Human Epidermal Growth Factor Receptor 2 (HER2) in Cancers: Overexpression and Therapeutic Implications. Mol Biol Int. 2014;852748.
7. de Melo Gagliato D, et al. Mechanisms of resistance and sensitivity to anti-HER2 therapies in HER2+ breast cancer. Oncotarget. 2016;7(39):64431-46.
8. National Comprehensive Cancer Network (NCCN). NCCN Guidelines Version 3.2020. Breast Cancer.
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