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 June 2023
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.
Lynparza approved in US for BRCAm prostate cancer
1
June 2023
Lynparza plus
abiraterone approved in the US for the treatment
of
BRCA-mutated metastatic castration-resistant prostate
cancer
Lynparza combination reduced the risk of disease progression or
death by 76% vs. abiraterone alone
First PARP inhibitor approved in combination with a new hormonal
agent underscores clinically meaningful benefit of new treatment
approach
AstraZeneca and MSD's Lynparza (olaparib) in combination with abiraterone
and prednisone or prednisolone has been approved in the US for the
treatment of adult patients with deleterious or suspected
deleterious BRCA-mutated (BRCAm) metastatic castration-resistant
prostate cancer (mCRPC).
This approval was based on a subgroup analysis of
the Phase III PROpel
trial which showed that Lynparza plus abiraterone
demonstrated highly clinically meaningful improvements in both
radiographic progression-free survival (rPFS) (HR of 0.24, 95% CI,
0.12-0.45) and overall survival (OS) (HR of 0.30, 95% CI,
0.15-0.59) versus abiraterone alone in patients with BRCA
mutations.1 Median rPFS and median OS were not reached for
patients treated with Lynparza plus abiraterone versus a median of 8 months
and 23 months, respectively, for those treated with abiraterone
alone.
Prostate cancer is the second-most common cancer
in men and despite an increase in the number of available therapies
for patients with mCRPC, five-year survival remains
low.2,3 Approximately
10% of patients with mCRPC have BRCA mutations, which is associated
with poor prognosis and outcomes.4,5
Andrew Armstrong, MD, ScM, of the Duke Cancer
Institute, Durham, North Carolina, US, and an investigator in the
trial, said: "Preventing or delaying radiographic progression or
death is an important clinical endpoint in assessing cancer
treatment and is very important to patients, their caregivers and
their families. The PROpel results showed
the Lynparza combination demonstrated a notable
clinically meaningful benefit that should rapidly be considered as
the standard of care treatment for patients with BRCA-mutated
metastatic castration-resistant prostate
cancer."
Dave Fredrickson, Executive Vice President,
Oncology Business Unit, AstraZeneca, said: "There is a
critical unmet need for new first-line treatment options for
patients with BRCA-mutated metastatic castration-resistant prostate
cancer and this approval underscores the importance of BRCA testing
at metastatic diagnosis. We look forward to bringing the benefit of
this Lynparza combination to patients earlier in their
treatment."
Eliav Barr, Senior Vice President, Head of Global
Clinical Development and Chief Medical Officer, MSD Research
Laboratories, said: "It is imperative that we create new ways to
treat advanced cancers and help improve patient outcomes by
building on the current standard of care. In PROpel,
the Lynparza combination improved radiographic
progression-free survival and overall survival for the subgroup of
patients with BRCA-mutated metastatic castration-resistant prostate
cancer. This approval reinforces the importance of routine testing
for genetic mutations at metastatic diagnosis to help guide
clinical decisions."
The
safety and tolerability profile of Lynparza plus abiraterone in
PROpel was in line with that observed in prior clinical trials and
the known profiles of the individual medicines.
Lynparza in combination with abiraterone and prednisone or
prednisolone is approved in the European Union (EU) and several
other countries for the treatment of adult patients with mCRPC
based on the PROpel trial.
Lynparza is already approved in the US based on
results from the PROfound Phase III
trial as monotherapy for
patients with homologous recombination repair (HRR) gene-mutated
mCRPC (BRCAm and other HRR gene mutations) who have progressed
following prior treatment with enzalutamide or abiraterone; and in
the EU, Japan, and China for patients with BRCAm mCRPC who have
progressed following prior therapy that included a new hormonal
agent.
Financial considerations
Following this approval
for Lynparza in the US, AstraZeneca will receive a
regulatory milestone payment from MSD, anticipated to be booked as
Collaboration Revenue by the Company and confirmed in the second
quarter 2023 results.
Notes
Prostate cancer
Prostate cancer is the second most commonly
diagnosed cancer in men and the fifth leading cause of cancer death
in men globally, with an incidence of 1.4 million and 375,000
deaths in 2020.2,3 In
the US, it is estimated that there will be 288,300 new cases and
34,700 deaths in 2023.6 Overall
survival for patients with mCRPC is approximately three years in
clinical trial settings, and even shorter in the
real-world.7 Approximately
half of patients with mCRPC may receive only one line of active
treatment, and those that go on to receive further treatment often
have diminishing benefit of subsequent
therapies.8-13
Metastatic castration-resistant prostate cancer
Metastatic prostate cancer is associated with a
significant mortality rate.14 Development
of prostate cancer is often driven by male sex hormones called
androgens, including testosterone.15
In patients with mCRPC, their prostate cancer
grows and spreads to other parts of the body despite the use of
androgen-deprivation therapy to block the action of male sex
hormones.16 Approximately
10-20% of men with advanced prostate cancer will develop
castration-resistant prostate cancer (CRPC) within five years, and
at least 84% of these men will have metastases at the time of CRPC
diagnosis.17 Of
patients with no metastases at CRPC diagnosis, 33% are likely to
develop metastases within two years.17
Despite the advances in mCRPC treatment in the
past decade with taxane and new hormonal agent (NHA) treatment,
there is high unmet need in this population.16-19
PROpel
PROpel is a randomised, double-blind, multi-centre
Phase III trial testing the efficacy, safety, and tolerability
of Lynparza versus placebo when given in combination
with abiraterone, as well as prednisone or prednisolone, in men
with mCRPC who had not received prior chemotherapy or NHAs in the
mCRPC setting.
The
primary endpoint is rPFS and secondary endpoints include OS, time
to secondary progression or death, and time to first subsequent
therapy. In September 2021 at a planned interim analysis, the
Independent Data Monitoring Committee concluded that the PROpel
trial met the primary endpoint of rPFS.
For more information about the trial please
visit ClinicalTrials.gov.
Lynparza
Lynparza (olaparib) is a first-in-class PARP
inhibitor and the first targeted treatment to block DNA damage
response (DDR) in cells/tumours harbouring a deficiency in HRR,
such as those with mutations in BRCA1 and/or BRCA2, or those where
deficiency is induced by other agents (such as
NHAs).
Inhibition of PARP with Lynparza leads to the trapping of PARP bound to DNA
single-strand breaks, stalling of replication forks, their collapse
and the generation of DNA double-strand breaks and cancer cell
death.
Lynparza is currently approved in a number of
countries across multiple tumour types including maintenance
treatment of platinum-sensitive relapsed ovarian cancer and as both
monotherapy and in combination with bevacizumab for the 1st-line
maintenance treatment of BRCA-mutated (BRCAm) and homologous
recombination repair deficient (HRD)-positive advanced ovarian
cancer, respectively; for gBRCAm, HER2-negative metastatic breast
cancer (in the EU and Japan this includes locally advanced breast
cancer); for gBRCAm, HER2-negative high-risk early breast cancer
(in Japan this includes all BRCAm HER2-negative high-risk early
breast cancer); for gBRCAm metastatic pancreatic cancer; in
combination with abiraterone for the treatment of metastatic
castration-resistant prostate cancer in whom chemotherapy is not
clinically indicated (EU) and as monotherapy in HRR gene-mutated
metastatic castration-resistant prostate cancer in patients who
have progressed on prior NHA treatment (BRCAm only in the EU and
Japan). In China, Lynparza is approved for the treatment of
BRCA-mutated metastatic castration-resistant prostate cancer, as a
1st-line maintenance therapy in BRCA-mutated advanced ovarian
cancer as well as 1st-line maintenance treatment with bevacizumab
for HRD-positive advanced ovarian cancer.
Lynparza, which is being jointly developed and
commercialised by AstraZeneca and MSD, has been used to treat over
75,000 patients worldwide. Lynparza has a broad clinical trial development
programme, and AstraZeneca and MSD are working together to
understand how it may affect multiple PARP-dependent tumours as a
monotherapy and in combination across multiple cancer
types. Lynparza is the foundation of AstraZeneca's
industry-leading portfolio of potential new medicines targeting DDR
mechanisms in cancer cells.
The AstraZeneca and MSD strategic oncology
collaboration
In July 2017,
AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US, known as
MSD outside the US and Canada, announced a global strategic
oncology collaboration to co-develop and
co-commercialise Lynparza,
the world's first PARP inhibitor, and Koselugo (selumetinib), a
mitogen-activated protein kinase (MEK) inhibitor, for multiple
cancer types.
Working together, the
companies will develop Lynparza and
Koselugo and other potential new medicines as monotherapies and as
combinations. The companies will also
develop Lynparza and
Koselugo in combination with their respective PD-L1 and PD-1
medicines independently.
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. Clarke N, et al. Abiraterone and Olaparib for Metastatic
Castration-Resistant Prostate Cancer. NEJM Evid. 2022;1(9).
2. Cancer.Net.
Prostate Cancer: Statistics. Available
at https://www.cancer.net/cancer-types/prostate-cancer/statistics. Accessed
March 2023.
3. Rawla P. Epidemiology of Prostate
Cancer. World J
Oncol. 2019;
10(2):63-89.
4.
de Bono, et al. Central, Prospective Detection of Homologous
Recombination Repair Gene Mutations (HRRm) in Tumour Tissue From
>4000 Men With Metastatic Castration-Resistant Prostate Cancer
(mCRPC) Screened for the PROfound Study. Presented at: ESMO
Congress; September 27-October 1, 2019; Barcelona, Spain. Abstract
847PD
5. Na R, et al. Germline Mutations in
ATM and BRCA1/2 Distinguish Risk for Lethal and Indolent Prostate
Cancer and are Associated with Early Age at
Death. Eur Urol. 2017;71(5):740-747.
6. 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;
71(3):209-249.
7. Cancer.Org. Key
Statistics For Prostate Cancer. Available at https://www.cancer.org/cancer/prostate-cancer/about/key-statistics.html. Accessed
March 2023.
8. Ng K, et al. Metastatic Hormone-Sensitive Prostate Cancer
(mHSPC): Advances and Treatment Strategies in the First-Line
Setting. Oncol Ther. 2020;8:209-230.
9. George DJ, et al. Treatment Patterns and Outcomes in Patients with
Metastatic Castration-Resistant Prostate Cancer in a Real-World
Clinical Practice Setting in the United
States. Clin Genitourin
Cancer.
2020;18:284-294.
10. de Bono
J, et
al. Antitumour Activity and Safety of
Enzalutamide in Patients with Metastatic Castration-Resistant
Prostate Cancer Previously Treated with Abiraterone Acetate Plus
Prednisone for ≥24 weeks in Europe. Eur
Urol.
2018;74(1):37-45
11. Hussein M, et al. Prostate-Specific Antigen Progression Predicts
Overall Survival in Patients with Metastatic Prostate Cancer: Data
from Southwest Oncology Group Trials 9346 (Intergroup Study 0162)
and 9916. J Clin
Oncol.
2009;27(15):2450.
12. de Wit,
R, et
al. Real-World Evidence of Patients
with Metastatic Castration-Resistant Prostate Cancer Treated with
Cabazitaxel: Comparison with the Randomized Clinical Study
CARD. Prostate
Cancer Prostatic Dis. 2022;2660.
13. Ryan C, et al. Abiraterone Acetate Plus Prednisone Versus
Placebo Plus Prednisone in Chemotherapy-Naive Men with Metastatic
Castration-Resistant Prostate Cancer (COU-AA-302): Final Overall
Survival Analysis of a Randomised, Double-Blind, Placebo-Controlled
Phase 3 Study. Lancet
Oncol. 2015
Feb;16(2):152-60.
14. Miller K, et al. The Phase 3 COU-AA-302 Study of Abiraterone
Acetate Plus Prednisone in Men with Chemotherapy-Naïve Metastatic
Castration-Resistant Prostate Cancer: Stratified Analysis Based on
Pain, Prostate-Specific Antigen, and Gleason
Score. Eur Urol. 2018;74(1):17-23.
15. Chowdhury S, et al. Real-World Outcomes in First-Line Treatment of
Metastatic Castration-Resistant Prostate Cancer: The Prostate
Cancer Registry. Target
Oncol.
2020;15(3):301-315.
16. Cancer.Net. Treatment
of Metastatic Castration-Resistant Prostate
Cancer. Available
at https://www.cancer.net/cancer-types/prostate-cancer/types-treatment. Accessed
March 2023.
17. Kirby M, et al. Characterising the Castration-Resistant
Prostate Cancer Population: Systematic
Review. Int J of Clin
Pract.
2021;65(11):1180-1192.
18. UroToday. What is
Changing in Advanced Prostate Cancer? Available
at https://www.urotoday.com/journal/everyday-urology-oncology-insights/articles/122176-what-is-changing-in-advanced-prostate-cancer.html. Accessed
March 2023.
19. Liu J, et al. Second-Line Hormonal Therapy for the Management
of Metastatic Castration-Resistant Prostate Cancer: A Real-World
Data Study Using a Claims Database. Sci Rep. 2020;10(1):4240.
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:
01 June 2023
|
|
By: /s/
Adrian Kemp
|
|
|
Name:
Adrian Kemp
|
|
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Title:
Company Secretary
|
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