TIDMAZN
RNS Number : 4270K
AstraZeneca PLC
05 May 2022
05 May 2022 07:10 BST
Enhertu approved in the US for patients with HER2-positive
metastatic
breast cancer treated with a prior anti-HER2-based regimen
Approval broadens indication for AstraZeneca and Daiichi
Sankyo's Enhertu to earlier use in metastatic breast cancer
Based on ground-breaking DESTINY-Breast03 results showing
Enhertu reduced the risk of disease progression or death by 72%
versus trastuzumab emtansine (T-DM1)
AstraZeneca and Daiichi Sankyo's Enhertu (trastuzumab
deruxtecan) has been approved in the US for the treatment of adult
patients with unresectable or metastatic HER2-positive breast
cancer who have received a prior anti-HER2-based regimen either in
the metastatic setting, or in the neoadjuvant or adjuvant setting
and have developed disease recurrence during or within six months
of completing therapy.
Enhertu is a specifically engineered HER2-directed antibody drug
conjugate (ADC) being jointly developed and commercialised by
AstraZeneca and Daiichi Sankyo.
The approval by the Food and Drug Administration (FDA) was based
on positive results from the DESTINY-Breast03 Phase III trial that
showed Enhertu reduced the risk of disease progression or death by
72% versus trastuzumab emtansine (T-DM1) (hazard ratio [HR] 0.28;
95% confidence interval [CI]: 0.22-0.37; p<0.0001) in patients
with HER2-positive unresectable and/or metastatic breast cancer
previously treated with trastuzumab and a taxane.
The approval was granted under the FDA's Real-Time Oncology
Review (RTOR) programme and converts the accelerated approval of
Enhertu in later line HER2-positive metastatic breast cancer to
standard approval, broadening Enhertu's breast cancer indication in
the US to earlier lines of use in patients with HER2-positive
metastatic breast cancer.
Erika Hamilton, MD, Director of the Breast Cancer and
Gynecological Cancer Research Program for Sarah Cannon Research
Institute, Nashville, Tennessee, US, said: "Enhertu has
demonstrated significant progression-free survival in the earlier
metastatic setting, potentially establishing it as a new standard
of care in previously treated patients with HER2-positive
metastatic breast cancer. Today's approval is an important
milestone for the clinical community as we will now be able to
offer Enhertu to these patients earlier in their treatment."
Catherine Ormerod, Executive Vice President, Strategy and
Mission, Living Beyond Breast Cancer, said: "This is an important
day for the breast cancer community. With this approval, Enhertu
now provides a new treatment option for patients with HER2-positive
metastatic breast cancer which can be used earlier in treatment to
potentially delay progression of disease."
Dave Fredrickson, Executive Vice President, Oncology Business
Unit, AstraZeneca, said: "Enhertu is already established in the
later-line treatment of patients with HER2-positive metastatic
breast cancer, and we are thrilled that with this approval,
patients in the US will now be able to access the transformative
potential of Enhertu earlier in their treatment. We look forward to
bringing this important, potentially paradigm-shifting medicine to
even more patients across the globe in an earlier setting as
quickly as possible."
Ken Keller, Global Head, Oncology Business and President and
CEO, Daiichi Sankyo, Inc, said: "Today's FDA approval, which
converts the accelerated approval of Enhertu to regular approval,
highlights the importance of the FDA's accelerated pathway that
allows for earlier approval of medicines to treat serious medical
conditions such as breast cancer. Data from DESTINY-Breast03 not
only confirmed the results of DESTINY-Breast01, but also
demonstrated the superiority of Enhertu in prolonging
progression-free survival compared to T-DM1 in an earlier setting
of HER2-positive metastatic breast cancer."
The DESTINY-Breast03 Phase III trial results were recently
published online in The New England Journal of Medicine.(1) In the
trial, 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.
Based on the DESTINY-Breast03 data , fam-trastuzumab
deruxtecan-nxki ( Enhertu ) recently was added to the NCCN Clinical
Practical Guidelines in Oncology (NCCN Guidelines (R) ) as the
Category 1 preferred regimen as second-line therapy for recurrent
unresectable (local or regional) or Stage IV HER2-positive
disease.(2)
The US regulatory submission was reviewed under Project Orbis,
which provides a framework for concurrent submission and review of
oncology medicines among participating international partners. Five
national health authorities collaborated with the FDA on this
review, including the Australian Therapeutic Goods Administration,
the Brazilian Health Regulatory Agency (ANVISA), Health Canada,
Israel's Ministry of Health Pharmaceutical Administration and
Switzerland's Swissmedic.
This approval follows the recent Priority Review and
Breakthrough Therapy Designation of Enhertu in the US in this
earlier setting.
Regulatory applications for Enhertu are currently under review
in Europe, Japan and several other countries for the treatment of
adult patients with unresectable or metastatic HER2-positive breast
cancer who have received a prior anti-HER2-based regimen based on
the results from the DESTINY-Breast03 trial.
Notes
Financial considerations
Following this approval for Enhertu in the US, an amount of
$100m is due from AstraZeneca to Daiichi Sankyo as a 2nd-line
milestone payment in HER2-positive metastatic breast cancer. In
AstraZeneca, the milestones paid will be capitalised as an addition
to the upfront payment made in 2019 and subsequent capitalised
milestones and amortised through the profit and loss.
Sales of Enhertu in the US are recognised by Daiichi Sankyo.
AstraZeneca reports its share of gross profit margin from Enhertu
sales in the US as collaboration revenue in the Company's financial
statements. For further details on the financial arrangements,
please consult the collaboration agreement from March 2019.
HER2-positive breast cancer
Breast cancer is the most common cancer and is one of the
leading causes of cancer-related deaths worldwide and in the
US.(3,4) More than two million patients with breast cancer were
diagnosed in 2020, with nearly 685,000 deaths globally.(3) More
than 290,000 new cases are expected in the US in 2022, with more
than 43,000 deaths.(5) Approximately one in five cases of breast
cancer are considered HER2-positive.(6)
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.(7) HER2 protein
overexpression may occur as a result of HER2 gene amplification and
is often associated with aggressive disease and poor prognosis in
breast cancer.(8)
Despite initial treatment with trastuzumab and a taxane,
patients with HER2-positive metastatic breast cancer will often
experience disease progression.(9) More treatment options are
needed to further delay progression and extend survival.(9-11)
DESTINY-Breast03
DESTINY-Breast03 is a global, head-to-head, randomised,
open-label, registrational Phase III trial evaluating the efficacy
and safety 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 (ORR), 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 the US for the treatment of
adult patients with unresectable or metastatic HER2-positive breast
cancer who have received a prior anti-HER2-based regimen either in
the metastatic setting, or in the neoadjuvant or adjuvant setting
and have developed disease recurrence during or within six months
of completing therapy, based on results from the DESTINY-Breast03
trial.
Enhertu (5.4mg/kg) is also approved in approximately 40
countries 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 based on the results from the
DESTINY-Breast01 trial.
Enhertu (6.4mg/kg) is approved in several countries 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.
Regulatory applications for Enhertu are currently under review
in Europe, Japan and several other countries for the treatment of
adult patients with unresectable or metastatic HER2-positive breast
cancer who have received a prior anti-HER2 based regimen based on
the results from the DESTINY-Breast03 trial.
Enhertu was granted Breakthrough Therapy Designation in the US
for the treatment of adult patients with unresectable or metastatic
HER2-low (IHC 1+ or IHC 2+/ISH-negative) breast cancer who have
received a prior systemic therapy in the metastatic setting or
developed disease recurrence during or within six months of
completing adjuvant chemotherapy, based on the results of the
DESTINY-Breast04 trial. Patients with hormone receptor (HR)
positive breast cancer should additionally have received or be
ineligible for endocrine therapy.
Enhertu is also currently under review in the US for the
treatment of adult patients with unresectable or metastatic
non-small cell lung cancer (NSCLC) whose tumours have a HER2
(ERBB2) mutation and who have received a prior systemic therapy,
based on the DESTINY-Lung01 trial, and in Europe for the treatment
of adult patients with locally advanced or metastatic HER2-positive
gastric or GEJ adenocarcinoma who have received a prior
anti-HER2-based regimen based on the DESTINY-Gastric01 and
DESTINY-Gastric02 trials.
Daiichi Sankyo collaboration
Daiichi Sankyo Company, Limited (TSE:4568) [referred to as
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 selective oestrogen receptor degrader (SERD)
and potential new medicine camizestrant.
PARP inhibitor Lynparza (olaparib) is a targeted treatment
option that has been studied in HER2-negative early and 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, evaluating 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
For details on how to contact the Investor Relations Team,
please click here . For Media contacts, click here .
References
1. Cortes J, et al. Trastuzumab Deruxtecan versus Trastuzumab
Emtansine for Breast Cancer. N Engl J Med 2022; 386:1143-1154.
2. Referenced with permission from the NCCN Clinical Practice
Guidelines in Oncology (NCCN Guidelines(R) ) for Breast Cancer
V2.2022. (c) National Comprehensive Cancer Network, Inc. 2022. All
rights reserved. Accessed May, 2022. To view the most recent and
complete version of the guideline, go online to NCCN.org. NCCN
makes no warranties of any kind whatsoever regarding their content,
use or application and disclaims any responsibility for their
application or use in any way.
3. 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.
4. Centers for Disease Control and Prevention. Available at:
https://gis.cdc.gov/Cancer/USCS/#/AtAGlance/ . Accessed May
2022.
5. American Cancer Society. Cancer Facts & Figures 2022.
Available at:
https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2022/2022-cancer-facts-and-figures.pdf.
Accessed May 2022.
6. 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.
7. Iqbal N, et al. Human Epidermal Growth Factor Receptor 2
(HER2) in Cancers: Overexpression and Therapeutic Implications. Mol
Biol Int. 2014;852748.
8. Pillai R, et al. HER2 mutations in lung adenocarcinomas: A
report from the Lung Cancer Mutation Consortium. Cancer.
2017;1;123(21):4099-4105.
9. Barok M, et al. Trastuzumab emtansine: mechanisms of action
and drug resistance. Breast Cancer Res. 2014; 16(2):209.
10. 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.
11. Martínez-Sáez O, et al. Current and Future Management of
HER2-Positive Metastatic Breast Cancer. JCO Oncol Pract. 2021.
10.1200/OP.21.00172.
Adrian Kemp
Company Secretary
AstraZeneca PLC
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