a4273k
FORM 6-K
SECURITIES
AND EXCHANGE COMMISSION
Washington,
D.C. 20549
Report
of Foreign Issuer
Pursuant
to Rule 13a-16 or 15d-16 of
the
Securities Exchange Act of 1934
For the
month of May 2022
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
CB2 0AA
United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Enhertu approved in US for 2L HER2+ breast cancer
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®)
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®)
for Breast Cancer V2.2022. © 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
SIGNATURES
Pursuant
to the requirements of the Securities Exchange Act of 1934, the
Registrant has duly caused this report to be signed on its behalf
by the undersigned, thereunto duly authorized.
Date:
05 May 2022
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By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
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