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 January 2025
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
CB2 0AA
United
Kingdom
Indicate
by check mark whether the registrant files or will file annual
reports under cover of Form 20-F or Form 40-F.
Form
20-F X Form 40-F __
Indicate
by check mark if the registrant is submitting the Form 6-K in paper
as permitted by Regulation S-T Rule 101(b)(1):
Indicate
by check mark if the registrant is submitting the Form 6-K in paper
as permitted by Regulation S-T Rule 101(b)(7): ______
Indicate
by check mark whether the registrant by furnishing the information
contained in this Form is also thereby furnishing the information
to the Commission pursuant to Rule 12g3-2(b) under the Securities
Exchange Act of 1934.
Yes __
No X
If
“Yes” is marked, indicate below the file number
assigned to the Registrant in connection with Rule 12g3-2(b):
82-_____________
AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Enhertu approved in US for breast cancer post ET
28 January 2025
Enhertu approved
in the US as first HER2-directed therapy for patients with HER2-low
or HER2-ultralow metastatic breast cancer following disease
progression after one or more endocrine
therapies
Based on DESTINY-Breast06 Phase III trial results which showed
Enhertu demonstrated superiority
vs. chemotherapy with a median progression-free survival of more
than one year
Approval brings AstraZeneca and Daiichi Sankyo's Enhertu to an
earlier HR-positive treatment setting and broadens the patient
population eligible for treatment with a HER2-directed therapy to
those with HER2-ultralow disease
AstraZeneca and Daiichi Sankyo's Enhertu (trastuzumab deruxtecan) has been
approved in the US for the treatment of adult patients
with unresectable or metastatic hormone receptor (HR)-positive,
HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow
(IHC 0 with membrane staining) breast cancer, as determined by
a Food and Drug Administration (FDA)-approved test, that has
progressed on one or more endocrine therapies in the metastatic
setting.
The approval was granted by the FDA after securing Priority Review
and Breakthrough Therapy Designation and was based on results from
the DESTINY-Breast06 Phase III trial, which were presented at the
2024 American Society of Clinical Oncology (ASCO) Meeting and
published in The
New England Journal of Medicine.
Aditya Bardia, MD, MPH, Program Director of Breast
Oncology and Director of Translational Research Integration, UCLA
Health Jonsson Comprehensive Cancer Center, US, and
investigator in the DESTINY-Breast06 trial, said: "Endocrine
therapy is typically used in the initial treatment of HR-positive
metastatic breast cancer and following progression, subsequent
chemotherapy is associated with poor
outcomes. With a median
progression-free survival exceeding one year and a response rate of
more than 60 per cent, trastuzumab deruxtecan offers a potential
new standard of care for patients
with HR-positive, HER2-low
or HER2-ultralow metastatic breast cancer following
endocrine therapy."
Dave Fredrickson, Executive Vice President, Oncology Haematology
Business Unit, AstraZeneca, said: "Building on the
practice-changing
previous approvals for Enhertu, this new approval brings this important
medicine to an earlier treatment setting and a broader patient
population with HER2-expressing metastatic breast cancer. The
approval also highlights the importance of testing metastatic
breast cancer tumours for detectable staining with a standard IHC
test to identify those who may be eligible for treatment
with Enhertu following endocrine
therapy."
Ken Keller, Global Head of Oncology Business, and President and
CEO, Daiichi Sankyo, said: "Enhertu continues to redefine the classification and
treatment of HR-positive metastatic breast cancer with important
new data across the spectrum of HER2 expression. Today's approval
underscores our ongoing commitment to realising the full potential
of this innovative antibody drug conjugate and represents another
paradigm shift in how certain breast cancers can be
treated."
Krissa Smith, Vice President, Education, Susan G. Komen, said: "We
are excited to see more treatment options for these patients which
enable more personalised care. It is critical for patients to
understand the HER2 status of their metastatic breast cancer to
help them make informed treatment decisions. Patients with tumours
that are HER2-low or HER2-ultralow now have more options to
consider with their healthcare team."
In the trial, Enhertu showed a 36% reduction in the risk of
disease progression or death versus chemotherapy (hazard ratio [HR]
0.64; 95% confidence interval [CI]: 0.54-0.76; p<0.0001) in the
overall trial population of patients with chemotherapy-naïve
HER2-low or HER2-ultralow metastatic breast cancer. A median
progression-free survival (PFS) of 13.2 months was seen in patients
randomised to Enhertu compared to 8.1 months in those randomised
to chemotherapy. The confirmed objective response rate (ORR) in the
overall trial population was 62.6% for Enhertu versus 34.4% for
chemotherapy.
In an exploratory analysis of patients with HER2-ultralow
expression, results were seen to be consistent between
patients with HER2-low expression and HER2-ultralow expression.
HER2 status in the trial was confirmed by a central laboratory and
was performed on a tumour sample obtained at the time of initial
metastatic diagnosis or later. Approximately 85-90% of patients
with HR-positive, HER2-negative metastatic breast cancer were
determined to have actionable levels of
HER2-expression.1 Further,
nearly two-thirds of patients previously assessed as IHC 0 at a
local laboratory were classified as HER2-low or HER2-ultralow upon
central analysis of the tumour sample.1
The safety profile of Enhertu in DESTINY-Breast06 was consistent with
previous clinical trials of Enhertu in
breast cancer with no new safety concerns
identified.
Enhertu is a specifically
engineered HER2-directed DXd antibody drug conjugate (ADC)
discovered by Daiichi Sankyo and being jointly developed and
commercialised by AstraZeneca and Daiichi
Sankyo.
Enhertu is already
approved in more than 70 countries, including the US, for patients
with HER2-low metastatic 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 from the DESTINY-Breast04 trial.
Regulatory applications are under review in the EU, Japan and
several other countries based on the DESTINY-Breast06
results.
Financial considerations
Following this approval for Enhertu in
the US, an amount of $175m is due from AstraZeneca to Daiichi
Sankyo as a milestone payment for the HER2-low and HER2-ultralow
chemotherapy-naïve breast cancer indication. The milestone
will be capitalised as an addition to the upfront payment made by
AstraZeneca to Daiichi Sankyo in 2019 and subsequent capitalised
milestones and will be amortised through the profit and loss
statement.
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 Alliance Revenue in the
Company's financial statements.
Further details on the financial arrangements were set out in
the March
2019 announcement of the
collaboration.
Notes
Breast cancer and HER2 expression
Breast cancer is the second most common cancer and one of the
leading causes of cancer-related deaths
worldwide.2 More
than two million breast cancer cases were diagnosed in 2022 with
more than 665,000 deaths globally.2 In
the US, more than 300,000 cases of breast cancer are diagnosed
annually.3 While
survival rates are high for those diagnosed with early breast
cancer, only about 30% of patients diagnosed with or who progress
to metastatic disease are expected to live five years following
diagnosis.4
HER2 is a tyrosine kinase receptor growth-promoting protein
expressed on the surface of many types of tumours, including breast
cancer.5 Patients
with high levels of HER2 expression (IHC 3+ or 2+/ISH+) are
classified as HER2-positive and treated with HER2-directed
therapies, representing approximately 15-20% of all breast
cancers.6 Historically,
tumours that were not classified as HER2-positive were classified
as HER2-negative.7
HR-positive, HER2-negative is the most common breast cancer
subtype, accounting for approximately 70% of all breast
cancers.4 Endocrine
therapies are widely given consecutively in the early lines of
treatment for HR-positive metastatic breast cancer. However, after
initial treatment, further efficacy from endocrine therapy is often
limited.8 The
current standard of care following endocrine therapy is
chemotherapy, which is associated with poor response rates and
outcomes.8-11
Despite being classified as HER2-negative, many of these tumours
may still carry some level of HER2 expression.7 Prior
to the approvals of Enhertu in HER2-low or HER2-ultralow metastatic
breast cancer based on the DESTINY-Breast04 and DESTINY-Breast06
trials, there were no targeted therapies specifically approved for
these patient populations.12,13
DESTINY-Breast06
DESTINY-Breast06 is a global, randomised, open-label, Phase III
trial evaluating the efficacy and safety of Enhertu (5.4mg/kg)
versus investigator's choice of chemotherapy (capecitabine,
paclitaxel or nab-paclitaxel) in patients with HR-positive,
HER2-low (IHC 1+ or 2+/ISH-) or HER2-ultralow (IHC 0 with membrane
staining) advanced or metastatic breast cancer. Patients in the
trial had no prior chemotherapy for advanced or metastatic disease
and received at least two lines of prior endocrine therapy in the
metastatic setting. Patients were also eligible if they had
received one prior line of endocrine therapy combined with a CDK4/6
inhibitor in the metastatic setting and experienced disease
progression within six months of starting 1st-line treatment or
received endocrine therapy as an adjuvant treatment and experienced
disease recurrence within 24 months.
The primary endpoint is PFS in the HR-positive, HER2-low patient
population as measured by blinded independent central review
(BICR). Key secondary endpoints include PFS by BICR in the overall
trial population (HER2-low and HER2-ultralow), overall survival
(OS) in the HER2-low patient population and OS in the overall trial
population. Other secondary endpoints include ORR, duration of
response, time to first subsequent treatment or death, time to
second subsequent treatment or death and safety.
DESTINY-Breast06 enrolled 866 patients (n=713 for HER2-low and
n=153 for HER2-ultralow) in Asia, Europe, Australia, North America
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 number of topoisomerase I inhibitor payloads (an
exatecan derivative, DXd) via tetrapeptide-based cleavable
linkers.
Enhertu (5.4mg/kg) is
approved in more than 75 countries worldwide for the treatment of
adult patients with unresectable or metastatic HER2-positive
(immunohistochemistry [IHC 3+ or in-situ hybridisation [ISH]+)
breast cancer who have received a (or one or more) 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 the results from the DESTINY-Breast03 trial.
Enhertu (5.4mg/kg) is
approved in more than 75 countries worldwide for the treatment of
adult patients with unresectable or metastatic HER2-low (IHC 1+ or
IHC 2+/ ISH-) 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 from the DESTINY-Breast04 trial.
Enhertu (5.4 mg/kg) is
approved in the US for adult patients with unresectable or
metastatic HR-positive, HER2-low (IHC 1+ or IHC 2+/ISH-)
or HER2-ultralow (IHC 0 with membrane staining) breast cancer,
as determined by an FDA-approved test, that has progressed on one
or more endocrine therapies in the metastatic setting based on
the results from the DESTINY-Breast06 trial.
Enhertu (5.4mg/kg) is approved in
more than 50 countries worldwide for the treatment of adult
patients with unresectable or metastatic non-small cell lung cancer
(NSCLC) whose tumours have activating HER2 (ERBB2)
mutations, as detected by a locally or regionally approved test,
and who have received a prior systemic therapy based on the results
from the DESTINY-Lung02 and/or DESTINY-Lung05 trials.
Continued approval in China and the US for this indication may be
contingent upon verification and description of clinical benefit in
a confirmatory trial.
Enhertu (6.4mg/kg) is
approved in more than 65 countries worldwide for the treatment of
adult patients with locally advanced or metastatic HER2-positive
(IHC 3+ or 2+/ISH+) gastric or gastroesophageal junction (GEJ)
adenocarcinoma who have received a prior trastuzumab-based regimen
based on the results from the DESTINY-Gastric01, DESTINY-Gastric02 and/or DESTINY-Gastric06 trials.
Continued approval in China for this indication will depend on
whether a randomised controlled confirmatory clinical trial can
demonstrate clinical benefit in this
population.
Enhertu (5.4mg/kg) is
approved in the US, Russia, Israel and Brazil for the treatment of
adult patients with unresectable or metastatic HER2-positive (IHC
3+) solid tumours who have received prior systemic treatment and
have no satisfactory alternative treatment options based on the
results from the DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 trials.
Continued approval for this indication in the US may be contingent
upon verification and description of clinical benefit in a
confirmatory trial.
Enhertu development programme
A comprehensive global clinical development programme is underway
evaluating the efficacy and safety of Enhertu monotherapy across multiple HER2-targetable
cancers. Trials in combination with other anti-cancer treatments,
such as immunotherapy, also are underway.
Daiichi Sankyo
collaboration
AstraZeneca and Daiichi Sankyo entered into a global collaboration
to jointly develop and commercialise Enhertu in March
2019 and Datroway (datopotamab deruxtecan)
in July
2020, except in Japan where
Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi
Sankyo is responsible for the manufacturing and supply
of Enhertu and Datroway.
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.
With Enhertu, a HER2-directed ADC, AstraZeneca and Daiichi
Sankyo are aiming to improve outcomes in previously treated
HER2-positive and HER2-low metastatic breast cancer and are
exploring its potential in earlier lines of treatment and in new
breast cancer settings.
In HR-positive breast cancer, AstraZeneca continues to improve
outcomes with foundational medicines Faslodex (fulvestrant) and Zoladex (goserelin)
and aims to reshape the HR-positive space with first-in-class AKT
inhibitor, Truqap (capivasertib), and next-generation SERD and
potential new medicine camizestrant. AstraZeneca is also
collaborating with Daiichi Sankyo to explore the potential of
TROP2-directed ADC, Datroway, in this setting.
PARP inhibitor Lynparza (olaparib) is a targeted treatment option
that has been studied in 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 these settings and to explore its
potential in earlier disease.
To bring much-needed treatment options to patients with
triple-negative breast cancer, an aggressive form of breast cancer,
AstraZeneca is evaluating the potential of Datroway alone and in combination with
immunotherapy Imfinzi (durvalumab), Truqap in
combination with chemotherapy, and Imfinzi in combination with other oncology
medicines, including Lynparza and Enhertu.
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's innovative
medicines are sold in more than 125 countries and used by millions
of patients worldwide. Please visit astrazeneca.com and
follow the Company on social media @AstraZeneca.
Contacts
For details on how to contact the Investor Relations Team, please
click here.
For Media contacts, click here.
References
1. Salgado RF, et al. LBA21 - Human
epidermal growth factor receptor 2 (HER2)-low and HER2-ultralow
status determination in tumors of patients (pts) with hormone
receptor-positive (HR+) metastatic breast cancer (mBC) in
DESTINY-Breast06 (DB-06). Annals of
Oncology. (2024) 35 (suppl_2):
1-72. 10.1016/annonc/annonc1623.
2. Bray F, et al. Global cancer
statistics 2022: GLOBOCAN estimates of incidence and mortality
worldwide for 36 cancers in 185 countries. CA Cancer J
Clin. 2024 Apr 4. doi:
10.3322/caac.21834.
3. American Cancer
Society. Key Statistics for Breast Cancer. Available
at: https://www.cancer.org/cancer/types/breast-cancer/about/how-common-is-breast-cancer.html. Accessed
January 2025.
4. National Cancer Institute.
Surveillance, Epidemiology and End Results
Program. Available at: https://seer.cancer.gov/statfacts/html/breast-subtypes.html. Accessed
January 2025.
5. Iqbal N, et al. Human Epidermal
Growth Factor Receptor 2 (HER2) in Cancers: Overexpression and
Therapeutic Implications. Mol Biol
Int.
2014;852748.
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. Sajjadi E, et al. Improving HER2
testing reproducibility in HER2-low breast
cancer. Cancer Drug
Resist. 2022;5(4):882-888.
8. Manohar P, et al. Updates in
endocrine therapy for metastatic breast
cancer. Cancer Biol
Med. 2022 Feb 15;
19(2):202-212.
9. Cortes J, et al. Eribulin
monotherapy versus treatment of physician's choice in patients with
metastatic breast cancer (EMBRACE): a phase 3 open-label randomised
study. Lancet. 2011;377:914-923.
10. Yuan P, et al. Eribulin mesilate versus
vinorelbine in women with locally recurrent or metastatic breast
cancer: A randomised clinical trial. Eur J
Cancer.
2019;112:57-65.
11. Jerusalem G, et al. Everolimus Plus
Exemestane vs Everolimus or Capecitabine Monotherapy for Estrogen
Receptor-Positive, HER2-Negative Advanced Breast
Cancer. JAMA Oncol. 2018;4(10):1367-1374.
12. Modi S, et al. Trastuzumab Deruxtecan in
Previously Treated HER2-Low Advanced Breast
Cancer. N Engl J
Med. 2022;387:9-20.
13. Bardia A, et al. Trastuzumab Deruxtecan
after Endocrine Therapy in Metastatic Breast
Cancer. N Eng J Med. 2024; 391:2110-2122.
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.
|
|
AstraZeneca
PLC
|
Date:
28 January 2025
|
|
By: /s/
Adrian Kemp
|
|
|
Name:
Adrian Kemp
|
|
|
Title:
Company Secretary
|