TIDMAZN
RNS Number : 8763N
AstraZeneca PLC
04 October 2021
4 October 2021 07:00 BST
Enhertu granted Breakthrough Therapy Designation in US for
patients with HER2-positive metastatic breast cancer treated with
one or more prior anti-HER2-based regimens
Based on ground-breaking DESTINY-Breast03 results where Enhertu
reduced the risk of disease progression or death by 72% vs.
trastuzumab emtansine (T-DM1)
Enhertu has now been granted four Breakthrough
Therapy Designations, including two in breast cancer
The Food and Drug Administration (FDA) has granted Enhertu
(trastuzumab deruxtecan), Breakthrough Therapy Designation (BTD) in
the US for the treatment of adult patients with unresectable or
metastatic HER2-positive breast cancer who have received one or
more prior anti-HER2-based regimens. Enhertu is a HER2-directed
antibody drug conjugate (ADC) jointly developed by AstraZeneca and
Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo).
The FDA granted BTD based on data from the DESTINY-Breast03
Phase III trial presented during the European Society for Medical
Oncology (ESMO) Congress 2021. This is the second BTD for Enhertu
in breast cancer and now brings the total number of BTDs to four
for this medicine.
The US FDA's BTD is designed to accelerate the development and
regulatory review of potential new medicines that are intended to
treat a serious condition and address a significant unmet medical
need. The new medicine needs to have shown encouraging preliminary
clinical results that demonstrate substantial improvement on a
clinically significant endpoint over available medicines.
Breast cancer remains the most common cancer worldwide, with
more than two million cases diagnosed in 2020, resulting in nearly
685,000 deaths globally.(1) Approximately one in five cases of
breast cancer are considered HER2-positive.(2)
Despite initial treatment with trastuzumab and a taxane,
patients with HER2-positive metastatic breast cancer will often
experience disease progression.(3) More effective options are
needed to further delay progression and extend survival.(3-5)
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: "This is an important step in bringing Enhertu
as a potential new option in earlier lines of treatment for
HER2-positive metastatic breast cancer, given the urgent need to
improve outcomes. This recognition by the FDA underscores the
transformative possibility of Enhertu seen with the remarkable
DESTINY-Breast03 results presented at ESMO just two weeks ago."
Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: " By
granting a fourth Breakthrough Therapy Designation to Enhertu, the
FDA continues to recognise the significant potential of this
medicine across multiple HER2-targetable tumours. With the
unprecedented data recently reported from the DESTINY-Breast03
trial, we look forward to working closely with the FDA to bring
Enhertu to patients who have been previously treated for
HER2-positive metastatic breast cancer as soon as possible. "
In DESTINY-Breast03, Enhertu demonstrated a 72% reduction in the
risk of disease progression or death compared to T-DM1 (hazard
ratio [HR] 0.28; 95% confidence interval [CI] 0.22-0.37;
p=7.8x10(-22) ) in patients with HER2-positive unresectable and/or
metastatic breast cancer previously treated with trastuzumab and a
taxane. Nearly all patients treated with Enhertu were alive at one
year (94.1%) compared to 85.9% of patients treated with T-DM1.
Confirmed objective response rate (ORR) more than doubled in the
Enhertu arm versus the T-DM1 arm (79.7% vs. 34.2%). The safety
profile of Enhertu was consistent with previous clinical trials,
with no new safety concerns identified and no Grade 4 or 5
treatment-related interstitial lung disease events.
Previous BTDs for Enhertu were in late-line HER2-positive
metastatic breast cancer in 2017 and HER2-mutant metastatic
non-small cell lung cancer (NSCLC) and HER2-positive metastatic
gastric cancer in 2020.
Enhertu is approved 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 in the
metastatic setting in the US, Japan, the EU and several other
countries based on the results from the DESTINY-Breast01 trial.
Enhertu is being further assessed in a comprehensive clinical
development programme evaluating efficacy and safety across
multiple HER2-targetable cancers, including breast, gastric, lung
and colorectal cancers.
HER2-positive breast cancer
Breast cancer remains the most common cancer and is one of the
leading causes of cancer-related deaths in women worldwide.(1) More
than two million patients with breast cancer were diagnosed in
2020, resulting in nearly 685,000 deaths globally.(1) Approximately
one in five cases of breast cancer are considered
HER2-positive.(2)
HER2 is a tyrosine kinase receptor growth-promoting protein
expressed on the surface of many types of tumours, including
breast, gastric, lung and colorectal cancers.(6) HER2 protein
overexpression may occur as a result of HER2 gene amplification and
is often associated with aggressive disease and a poor prognosis in
breast cancer.(7)
Despite initial treatment with trastuzumab and a taxane, people
with HER2-positive metastatic breast cancer will often experience
disease progression.(3) More effective options are needed to
further delay progression and extend survival.(3-5)
DESTINY-Breast03
DESTINY-Breast03 is a global head-to-head, randomised,
open-label, registrational Phase III trial evaluating the safety
and efficacy of Enhertu (5.4mg/kg) versus T-DM1 in patients with
HER2-positive unresectable and/or metastatic breast cancer
previously treated with trastuzumab and a taxane.
The primary efficacy endpoint of DESTINY-Breast03 is
progression-free survival (PFS) based on blinded independent
central review. Secondary efficacy endpoints include overall
survival, objective response rate, duration of response, PFS based
on investigator assessment and safety.
DESTINY-Breast03 enrolled approximately 500 patients at multiple
sites in Asia, Europe, North America, Oceania and South America.
For more information about the trial, visit ClinicalTrials.gov
.
Enhertu
Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo's
proprietary DXd ADC technology, Enhertu is the lead ADC in the
oncology portfolio of Daiichi Sankyo and the most advanced
programme in AstraZeneca's ADC scientific platform. Enhertu
consists of a HER2 monoclonal antibody attached to a topoisomerase
I inhibitor payload, an exatecan derivative, via a stable
tetrapeptide-based cleavable linker.
Enhertu (5.4mg/kg) is approved in Canada, the EU, Israel, Japan,
the UK and the US 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 in the
metastatic setting based on the results from the DESTINY-Breast01
trial.
Enhertu (6.4mg/kg) is also approved in Israel, Japan and the US
for the treatment of adult patients with locally advanced or
metastatic HER2-positive gastric or gastroesophageal junction
adenocarcinoma who have received a prior trastuzumab-based regimen
based on the results from the DESTINY-Gastric01 trial.
Enhertu development programme
A comprehensive development programme is underway globally,
evaluating the efficacy and safety of Enhertu monotherapy across
multiple HER2-targetable cancers, including breast, gastric, lung
and colorectal cancers. Trials in combination with other anticancer
treatments, such as immunotherapy, are also underway.
Enhertu was highlighted in the Clinical Cancer Advances 2021
report as one of two significant advancements in the "ASCO Clinical
Advance of the Year: Molecular Profiling Driving Progress in GI
Cancers", based on data from both the DESTINY-CRC01 and
DESTINY-Gastric01 trials, as well as one of the targeted therapy
advances of the year in NSCLC, based on the interim results of the
HER2-mutated cohort of the DESTINY-Lung01 trial.
Daiichi Sankyo collaboration
Daiichi Sankyo and AstraZeneca entered into a global
collaboration to jointly develop and commercialise Enhertu (a
HER2-directed ADC) in March 2019, and datopotamab deruxtecan
(DS-1062; a TROP2-directed ADC) in July 2020, except in Japan where
Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is
responsible for manufacturing and supply of Enhertu and datopotamab
deruxtecan.
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 oral SERD and potential new medicine
camizestrant.
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
Canada) continue to research Lynparza in metastatic breast cancer
patients with an inherited BRCA mutation and are exploring new
opportunities to treat these patients earlier in their disease.
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 Imfinzi (durvalumab) in
combination with other oncology medicines, including Lynparza and
Enhertu, investigating 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 is leading a revolution in oncology with the
ambition to provide cures for cancer in every form, following the
science to understand cancer and all its complexities to discover,
develop and deliver life-changing medicines to patients.
The Company's focus is on some of the most challenging cancers.
It is through persistent innovation that AstraZeneca has built one
of the most diverse portfolios and pipelines in the industry, with
the potential to catalyse changes in the practice of medicine and
transform the patient experience.
AstraZeneca has the vision to redefine cancer care and, one day,
eliminate cancer as a cause of death.
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led
biopharmaceutical company that focuses on the discovery,
development, and commercialisation of prescription medicines in
Oncology, Rare Diseases, and BioPharmaceuticals, including
Cardiovascular, Renal & Metabolism, and Respiratory &
Immunology. Based in Cambridge, UK, AstraZeneca operates in over
100 countries and its innovative medicines are used by millions of
patients worldwide. Please visit astrazeneca.com and follow the
Company on Twitter @ AstraZeneca.
Contacts
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References
1. Sung H, et al. Global Cancer Statistics 2020: GLOBOCAN
Estimates of Incidence and Mortality Worldwide for 36 Cancers in
185 Countries. CA Cancer J Clin. 2021; 10.3322/caac.21660.
2. Ahn S, et al. HER2 status in breast cancer: changes in
guidelines and complicating factors for interpretation. J Pathol
Transl Med. 2020; 54(1): 34-44.
3. Barok M, et al. Trastuzumab emtansine: mechanism of action
and drug resistance. Breast Cancer Res. 2014; 16(2):209.
4. Mounsey, L et al. Changing Natural History of HER2-Positive
Breast Cancer Metastatic to the Brain in the Era of New Targeted
Therapies. Clin Breast Cancer. 2018; 18(1):29-37.
5. Martinez-S Sáez O, et al. Current and Future Management of
HER2-Positive Metastatic Breast Cancer. JCO Oncol Pract. 2021.
10.1200/OP.21.00172.
6. Iqbal N, et al. Human Epidermal Growth Factor Receptor 2
(HER2) in Cancers: Overexpression and Therapeutic Implications. Mol
Biol Int. 2014;852748.
7. Pillai R, et al. HER2 mutations in lung adenocarcinomas: A
report from the Lung Cancer Mutation Consortium. Cancer.
2017;1;123(21):4099-4105.
Adrian Kemp
Company Secretary
AstraZeneca PLC
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