REG - AstraZeneca PLC - Lynparza approved in China for prostate cancer

AstraZenecaAnnouncement

24/06/2021 07:00

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RNS Number : 9216C  AstraZeneca PLC  24 June 2021

 

24 June 2021 07:00 BST

 

Lynparza approved in China for the treatment of BRCA-

mutated metastatic castration-resistant prostate cancer

 

Only PARP inhibitor to improve overall survival versus

new hormonal treatments in advanced prostate cancer

 

First PARP inhibitor approved in China in advanced prostate cancer

 

AstraZeneca and MSD's Lynparza (olaparib) has been granted conditional
approval in China to treat adult patients with germline or somatic
BRCA-mutated metastatic castration-resistant prostate cancer (mCRPC) who have
progressed following treatment that included a new hormonal agent
(abiraterone, enzalutamide).

 

In China, prostate cancer is the sixth most prevalent cancer in men, with
approximately 115,000 new patients diagnosed each year and about 7% have
germline BRCA mutations.(1,2) Prostate cancer patients with these mutations
are more likely to have poorer outcomes than those without the mutations.(3)
Around 70% of prostate cancer patients in China have advanced disease at the
time of diagnosis, and for those with mCRPC, the median survival is less than
two years.(4,5)

 

The approval by China's National Medical Products Administration was based on
a subgroup analysis of the PROfound Phase III trial, which showed that
Lynparza demonstrated a substantial improvement in radiographic
progression-free survival (rPFS) and overall survival (OS) versus abiraterone
or enzalutamide in men with BRCA1/2 mutations. Continued approval is
contingent upon verification and description of clinical benefit in a planned
bridging trial with Chinese patients.

 

Dave Fredrickson, Executive Vice President, Oncology Business Unit, said:
"This approval begins a new era of precision medicine for patients in China
with advanced prostate cancer who have historically had a poor prognosis and
few treatment options. Lynparza more than tripled radiographic
progression-free survival in the PROfound trial and is the only PARP inhibitor
to show an overall survival benefit compared to treatment with new hormonal
agents for men with BRCA-mutated metastatic castration-resistant prostate
cancer."

 

Roy Baynes, Senior Vice President and Head of Global Clinical Development,
Chief Medical Officer, MSD Research Laboratories, said: "The approval
underscores the critical importance of BRCA testing in men with prostate
cancer. We are proud to provide a new personalised treatment option for men
with this devastating disease in China, and we will continue to collaborate
with the Chinese government and healthcare organisations to bring Lynparza to
patients who need it."

 

The subgroup analysis from the PROfound Phase III trial showed Lynparza
reduced the risk of disease progression or death by 78% (based on a hazard
ratio  HR  of 0.22, 95% confidence interval  CI  0.15-0.32; nominal
p<0.0001) and improved rPFS to a median of 9.8 months versus 3.0 with
abiraterone or enzalutamide in men with mCRPC with BRCA1/2 mutations. In
addition, Lynparza reduced the risk of death by 37% (HR of 0.63, 95% CI
0.42-0.95) with median OS of 20.1 months versus 14.4 with abiraterone or
enzalutamide.

 

The primary results (https://www.nejm.org/doi/full/10.1056/NEJMoa1911440) and
OS results (https://www.nejm.org/doi/10.1056/NEJMoa2022485) from the PROfound
Phase III trial were published in The New England Journal of Medicine.

 

Lynparza is approved in the US
(https://www.astrazeneca.com/media-centre/press-releases/2020/lynparza-approved-in-the-us-for-hrr-gene-mutated-metastatic-castration-resistant-prostate-cancer.html)
to treat men with homologous recombination repair gene-mutated (HRRm) mCRPC
and in the EU
(https://www.astrazeneca.com/media-centre/press-releases/2020/lynparza-approved-in-the-eu-for-prostate-cancer.html)
, Japan
(https://www.astrazeneca.com/media-centre/press-releases/2020/lynparza-approved-in-japan-for-three-cancers.html)
and several other countries for BRCA-mutated mCRPC patients based on the
PROfound Phase III trial. In addition, regulatory reviews are ongoing in other
countries around the world.

 

AstraZeneca and MSD are testing Lynparza in additional trials in metastatic
prostate cancer, including the ongoing PROpel Phase III trial of Lynparza as a
1st-line treatment for patients with mCRPC in combination with abiraterone
versus abiraterone alone. Results are anticipated in the second half of 2021.

 

Metastatic castration-resistant prostate cancer

Prostate cancer is associated with a significant mortality rate.(6) Prostate
cancer is often driven by male sex hormones called androgens, including
testosterone.(7) In patients with mCRPC, 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.(7) Approximately 10-20% of men with
advanced prostate cancer will develop CRPC within five years, and at least 84%
of these men will have metastases at the time of CRPC diagnosis.(8) Of men
with no metastases at CRPC diagnosis, 33% are likely to develop metastases
within two years.(8) Despite advances in treatment for men with mCRPC,
five-year survival is low and extending survival remains a key treatment
goal.(8)

 

PROfound

PROfound is a prospective, multicentre, randomised, open-label, Phase III
trial testing the efficacy and safety of Lynparza versus abiraterone or
enzalutamide in patients with mCRPC who have progressed on prior treatment
that included new hormonal agents (abiraterone or enzalutamide) and have a
qualifying tumour mutation in BRCA1/2, ATM or one of 12 other genes involved
in the HRRm pathway.

 

The trial was designed to analyse patients with HRR gene mutations in two
cohorts: the primary endpoint was rPFS in those with mutations in BRCA1/2 or
ATM genes, and then, if Lynparza showed clinical benefit, a formal analysis
was performed of the overall trial population of patients with HRR gene
mutations (BRCA1/2, ATM and 12 other HRR gene mutations). AstraZeneca and MSD
announced in August 2019
(https://www.astrazeneca.com/media-centre/press-releases/2019/lynparza-phase-iii-profound-trial-in-hrr-mutation-selected-metastatic-castration-resistant-prostate-cancer-met-primary-endpoint-07082019.html)
that the trial met its primary endpoint of rPFS.

 

BRCA1 and BRCA2

BRCA1 and BRCA2 are human genes that produce proteins responsible for
repairing damaged DNA and play an important role maintaining the genetic
stability of cells. When either of these genes is mutated or altered such that
its protein product either is not made or does not function correctly, DNA
damage may not be repaired properly, and cells become unstable. As a result,
cells are more likely to develop additional genetic alterations that can lead
to cancer and confer sensitivity to PARP inhibitors, including Lynparza.(9-12)

 

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 mutations in BRCA1 and/or BRCA2. 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 being tested in a
range of PARP-dependent tumour types with defects and dependencies in the DDR
pathway.

 

Lynparza is currently approved in several countries, including those in the
EU, for the maintenance treatment of platinum-sensitive relapsed ovarian
cancer. It is approved in the US, the EU, Japan, China, and several other
countries as 1st-line maintenance treatment of BRCA-mutated (BRCAm) advanced
ovarian cancer following response to platinum-based chemotherapy. It is also
approved in the US, the EU, and Japan as 1st-line maintenance treatment with
bevacizumab for patients with HRD-positive advanced ovarian cancer (BRCAm
and/or genomic instability). In addition, Lynparza is approved in the US,
Japan, and several other countries for germline BRCAm, HER2-negative,
metastatic breast cancer, previously treated with chemotherapy; in the EU,
this includes locally advanced breast cancer. It is also approved in the US,
the EU, Japan, and several other countries to treat germline BRCAm metastatic
pancreatic cancer. In addition, Lynparza is approved in the US for HRR
gene-mutated mCRPC (BRCAm and other HRR gene mutations) and in the EU and
Japan for BRCAm metastatic castration-resistant prostate cancer. Regulatory
reviews are underway in several countries for ovarian, breast, pancreatic and
prostate cancers.

 

Lynparza, which is being jointly developed and commercialised by AstraZeneca
and MSD, has been used to treat over 40,000 patients worldwide. Lynparza has
the broadest and most advanced clinical trial development programme of any
PARP inhibitor. 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 in combination with other potential new
medicines and as monotherapies. Independently, the companies will develop
Lynparza and Koselugo in combination with their respective PD-L1 and PD-1
medicines.

 

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 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
(https://www.astrazeneca.com/investor-relations.html#Contacts) . For Media
contacts, click here (https://www.astrazeneca.com/media-centre/contacts.html)
.

 

References

1. Gco.iarc.fr. Cancer today - Estimated number of new cases in 2020, Asia,
worldwide, China, males, all ages. Available at:
https://gco.iarc.fr/today/online-analysis-table
(https://gco.iarc.fr/today/online-analysis-table) Accessed June 2021.

2. Wei, Y., et al. Germline DNA Repair Gene Mutation Landscape in Chinese
Prostate Cancer Patients. European Urology,2019,76(3), pp.280-283.

3. Messina, C., et al. BRCA Mutations in Prostate Cancer: Prognostic and
Predictive Implications. Journal of Oncology, 2020, pp.1-7.

4. National Health Commission of PRC, Chinese guidelines for diagnosis and
treatment of prostate cancer 2018 (English version). Chinese Journal of Cancer
Research, 2019,31(1), pp.67-83.

5. Zhu, Y., et al. Chinese Expert Consensus on the Diagnosis and Treatment of
Castration-Resistant Prostate Cancer (2019 update). Cancer Manag Res. 2020;
12: 2127-2140.

6. Bray, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence
and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal
for Clinicians, 2018,68(6), pp.394-424.

7. de Bono, et al. Olaparib for Metastatic Castration-Resistant Prostate
Cancer. New England Journal of Medicine, 2020,382,pp.2091-102.

8. Cancer.Net. Treatment of metastatic castration-resistant prostate cancer.
Available at:
https://www.cancer.net/research-and-advocacy/asco-care-and-treatment-recommendations-patients/treatment-metastatic-castration-resistant-prostate-cancer
(https://www.cancer.net/research-and-advocacy/asco-care-and-treatment-recommendations-patients/treatment-metastatic-castration-resistant-prostate-cancer)
. Accessed June 2021.

9. Kirby, M. (2011). Characterising the castration-resistant prostate cancer
population: a systematic review. International Journal of Clinical Practice,
65(11), pp.1180-1192.

10. Roy R, et al. (2012). BRCA1 and BRCA2: different roles in a common pathway
of genome protection. Nat Rev Cancer. 2011;12(1):68-78. Published 2011 Dec 23.
doi:10.1038/nrc3181.

11. Wu J, et al. (2010) The role of BRCA1 in DNA damage response. Protein
Cell. 2010;1(2):117-123.

12. Gorodetska I, et al. (2019). BRCA Genes: The Role in Genome Stability,
Cancer Stemness and Therapy Resistance. J Cancer. 2019;10(9):2109-2127.

 

Adrian Kemp

Company Secretary

AstraZeneca PLC

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