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

AstraZenecaAnnouncement

22/09/2022 07:00

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RNS Number : 2779A  AstraZeneca PLC  22 September 2022

22 September 2022 07:00 BST

 

Lynparza approved in China as 1st-line maintenance treatment with bevacizumab
for HRD-positive advanced ovarian cancer

 

One in two women with advanced ovarian cancer has an HRD-positive tumour
 

AstraZeneca and MSD's Lynparza (olaparib) has been approved in China for the
maintenance treatment of adult patients with advanced epithelial ovarian,
fallopian tube or primary peritoneal cancer who are in complete or partial
response to 1st-line platinum-based chemotherapy in combination with
bevacizumab, and whose cancer is associated with homologous recombination
deficiency (HRD)-positive status.

 

In China, ovarian cancer is the third most common gynaecologic cancer, with a
five-year survival rate of approximately 39%, largely because more than 70% of
women are diagnosed with advanced disease (Stage III or IV).(1,2) In 2020,
there were over 55,000 new cases of ovarian cancer in China.(3)

 

The approval by China's National Medical Products Administration was based on
an HRD-positive subgroup exploratory analysis of the PAOLA-1 Phase III trial
which showed Lynparza plus bevacizumab demonstrated a substantial
progression-free survival (PFS) improvement versus bevacizumab alone for
patients with HRD-positive advanced ovarian cancer. During European Society
for Medical Oncology Congress (ESMO) 2022, the final overall survival (OS)
results
(https://www.astrazeneca.com/media-centre/press-releases/2022/lynparza-in-combination-with-bevacizumab-demonstrates-clinically-meaningful-survival-benefit-in-advanced-ovarian-cancer.html)
were presented from the PAOLA-1 Phase III trial demonstrating that Lynparza
plus bevacizumab provided a clinically meaningful improvement in overall
survival in HRD-positive advanced ovarian cancer.

 

Professor Ding Ma, Member of the Chinese Academy of Engineering, said:
"Ovarian cancer has the highest fatality rate among gynaecologic cancers in
China. The emergence of PARP inhibitors and their application in the 1st-line
treatment of ovarian cancer could help patients delay disease progression and
achieve long-term remission. In the PAOLA-1 trial, the combination of olaparib
and bevacizumab demonstrated clinically meaningful improvements in overall
survival. This approval provides HRD-positive patients with a new option for
1st-line maintenance therapy."

 

Professor Beihua Kong, Chairman of the Gynaecological Oncology Branch of the
Chinese Medical Association, said: "Ovarian cancer has entered the era of
precision medicine, and HRD detection (including BRCA1/2 mutations) has
important clinical value for newly diagnosed patients with advanced ovarian
cancer, to help guide first-line treatment decisions. The approval of the
combination of olaparib and bevacizumab brings a clinically meaningful
survival benefit to HRD-positive patients, and further reflects the importance
of a precision approach to help guide treatment decisions in ovarian cancer."

 

Dave Fredrickson, Executive Vice President, Oncology Business Unit,
AstraZeneca, said: "The maintenance treatment of Lynparza in combination with
bevacizumab has shown to both improve progression-free survival and provide a
clinically meaningful improvement in overall survival in patients with
HRD-positive advanced ovarian cancer following response to platinum-based
chemotherapy. I am thrilled we can now bring this targeted treatment option to
these patients in China."

 

Dr Eliav Barr, Senior Vice President, Head of Global Clinical Development and
Chief Medical Officer, MSD Research Laboratories, said: "This approval is an
important milestone for patients with newly diagnosed advanced ovarian cancer
in China and underscores the critical importance of HRD testing for all women
with advanced ovarian cancer at the point of diagnosis."

 

The initial results
(https://www.astrazeneca.com/media-centre/press-releases/2019/lynparza-improved-the-time-women-lived-without-disease-progression-to-22-months-in-the-broad-population-and-to-37-months-in-hrd-positive-patients.html)
from the PAOLA-1 Phase III trial showed that Lynparza plus bevacizumab reduced
the risk of disease progression or death by 67% in the subgroup of patients
with HRD-positive advanced ovarian cancer (based on a hazard ratio  HR  of
0.33; 95% confidence interval  CI  0.25-0.45 from the pre-specified
exploratory analysis). Lynparza plus bevacizumab also improved PFS to a
median of 46.8 versus 17.6 months with bevacizumab alone in this patient
population. The primary endpoint in the intent-to-treat population was a
statistically significant and clinically meaningful improvement in PFS. The
data from the PAOLA-1 trial was published in The New England Journal of
Medicine (https://www.nejm.org/doi/full/10.1056/NEJMoa1911361) in 2019.

 

Further results
(https://www.astrazeneca.com/media-centre/press-releases/2022/lynparza-in-combination-with-bevacizumab-demonstrates-clinically-meaningful-survival-benefit-in-advanced-ovarian-cancer.html)
from the five-year analysis of the PAOLA-1 trial recently presented at the
ESMO 2022 showed Lynparza plus bevacizumab increased median overall survival
to 56.5 months versus 51.6 months with bevacizumab alone, in patients with
newly diagnosed advanced ovarian cancer irrespective of HRD status. This
increase was not statistically significant. In HRD-positive patients, Lynparza
plus bevacizumab provided a clinically meaningful improvement in overall
survival, reducing the risk of death by 38% versus bevacizumab (based on a HR
of 0.62; 95% CI 0.45-0.85 from the pre-specified exploratory sub-group
analysis) despite PAOLA-1 having 30% Stage IV patients. The safety and
tolerability profile of Lynparza in this trial was in line with that observed
in prior clinical trials, with no new safety signals.

 

Lynparza in combination with bevacizumab is approved in the US
(https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2020/tlynparza-approved-in-the-us-as-1st-line-maintenance-treatment-with-bevacizumab-for-hrd-positive-advanced-ovarian-cancer.html)
,  and several other countries as a 1st-line maintenance treatment for
patients with HRD-positive advanced ovarian cancer and is currently under
regulatory review in other countries around the world. In China, Lynparza is
approved
(https://www.astrazeneca.com/media-centre/press-releases/2021/lynparza-approved-in-china-for-prostate-cancer.html)
for the treatment of BRCA-mutated metastatic castration-resistant prostate
cancer as well as a 1st-line maintenance therapy in BRCA-mutated advanced
ovarian cancer
(https://www.astrazeneca.com/media-centre/press-releases/2019/lynparza-approved-in-china-as-a-1st-line-maintenance-therapy-in-brca-mutated-advanced-ovarian-cancer.html#!)
.

 

Notes

 

Ovarian cancer

Ovarian cancer is the eighth most common cancer in women worldwide.(4) There
were more than 313,000 new cases of ovarian cancer in 2020, and over 207,000
deaths. The 5-year survival rate of newly diagnosed advanced ovarian cancer
patients has typically been 30-50%.(5,6) Roughly half of women with advanced
ovarian cancer have homologous recombination deficiency (HRD)-positive tumours
including those with a BRCA mutation and up to one in five women have a BRCA
mutation.(7-9) The primary aim of 1st-line treatment is to delay disease
progression for as long as possible with the intent to achieve long-term
remission.(10-12)

 

PAOLA-1

PAOLA-1 is a double-blinded Phase III trial testing the efficacy and safety
of Lynparza added to standard of care bevacizumab versus bevacizumab
alone, as a 1st-line maintenance treatment for newly diagnosed advanced FIGO
Stage III-IV high-grade serous or endometroid ovarian, fallopian tube, or
peritoneal cancer patients who had a complete or partial response to 1st-line
treatment with platinum-based chemotherapy and bevacizumab. AstraZeneca and
MSD announced in August 2019
(https://www.astrazeneca.com/media-centre/press-releases/2019/lynparza-phase-iii-paola-1-trial-met-primary-endpoint-as-1st-line-maintenance-treatment-with-bevacizumab-for-advanced-ovarian-cancer-14082019.html)
that the trial met its primary endpoint of PFS in the overall trial
population.

 

The primary analysis of the PAOLA-1 Phase III trial showed that Lynparza, in
combination with bevacizumab maintenance treatment, reduced the risk of
disease progression or death by 67% (based on a HR of 0.33; 95% CI 0.25-0.45)
in the subgroup of patients with HRD-positive advanced ovarian cancer. The
addition of Lynparza improved PFS to a median of 46.8 months versus 17.6 with
bevacizumab alone in this patient population.

 

Updated results from the five-year analysis of the PAOLA-1 Phase III trial
demonstrate that in a pre-specified exploratory subgroup analysis of
HRD-positive patients, Lynparza plus bevacizumab provided a clinically
meaningful improvement in overall survival, reducing the risk of death by 38%
versus bevacizumab (based on a HR of 0.62; 95% CI 0.45-0.85). In addition,
65.5% of patients treated with Lynparza plus bevacizumab were still alive at
five years versus 48.4% of those treated with bevacizumab alone. Lynparza plus
bevacizumab also improved median PFS to almost four years (46.8 months) versus
17.6 months with bevacizumab plus placebo, and 46.1% of patients treated with
Lynparza plus bevacizumab remain progression free at five years versus 19.2%
of patients treated with bevacizumab alone.

 

PAOLA-1 is an ENGOT (European Network of Gynaecological Oncological Trial
groups) trial, sponsored by ARCAGY Research (Association de Recherche sur les
CAncers dont GYnécologiques) on behalf of GINECO (Groupe d'Investigateurs
National des Etudes des Cancers Ovariens et du sein), lead group for the
PAOLA-1 trial. ARCAGY-GINECO is an academic group specialising in clinical and
translational research in patients' gynaecological cancers, labelled by the
French National Cancer Institute (INCa), and a member of the GCIG (Gynecologic
Cancer InterGroup).

 

Homologous recombination deficiency

HRD, which defines a subgroup of ovarian cancer, encompasses a wide range of
genetic abnormalities, including BRCA mutations and beyond. As with BRCA gene
mutations, HRD interferes with normal cell DNA repair mechanisms and confers
sensitivity to PARP inhibitors including Lynparza.(13)

 

Lynparza
Lynparza (olaparib) is a 1st-in-class PARP inhibitor and the first targeted
treatment to block DNA damage response (DDR) in cells/tumours harbouring a
deficiency in homologous recombination repair (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 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 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; and HRR gene-mutated metastatic
castration-resistant prostate cancer (BRCAm only in the EU and Japan). In
China, Lynparza is approved
(https://www.astrazeneca.com/media-centre/press-releases/2021/lynparza-approved-in-china-for-prostate-cancer.html)
for the treatment of BRCA-mutated metastatic castration-resistant prostate
cancer as well as a 1(st)-line maintenance therapy in BRCA-mutated advanced
ovarian cancer
(https://www.astrazeneca.com/media-centre/press-releases/2019/lynparza-approved-in-china-as-a-1st-line-maintenance-therapy-in-brca-mutated-advanced-ovarian-cancer.html#!)
.

 

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 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.

 

By harnessing the power of six scientific platforms - Immuno-Oncology, Tumour
Drivers and Resistance, DNA Damage Response, Antibody Drug Conjugates,
Epigenetics, and Cell Therapies - and by championing the development of
personalised combinations, AstraZeneca has the vision to redefine cancer
treatment 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, primarily for the treatment of diseases in three
therapy areas - Oncology, 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 (http://www.astrazeneca.com/)
and follow the Company on Twitter @AstraZeneca
(https://twitter.com/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.   Jiang X, et al. Epidemiology of gynecologic cancers in China. J Gynecol
Oncol. 2018 Jan; 29(1): e7.

2.   Bu H, et al. BRCA mutation frequency and clinical features of ovarian
cancer patients: A report from a Chinese study group. J Obstet Gynaecol Res.
2019 Nov;45(11):2267-2274.

3.   Globocan. China Globocan 2020. Available at
https://gco.iarc.fr/today/data/factsheets/populations/160-china-fact-sheets.pdf
(https://gco.iarc.fr/today/data/factsheets/populations/160-china-fact-sheets.pdf)
. Accessed September 2022.

4.   Momenimovahed Z, et al. Ovarian Cancer in The World: Epidemiology And
Risk Factors. Int J Womens Health. 2019 Apr 30;11:287-299.

5.   Torre A, et al. Ovarian Cancer Statistics. CA Cancer J Clin. 2018
Jul; 68(4):284-296.

6.   National Cancer Institute. Cancer Stat Facts: Ovarian Cancer. Available
at https://seer.cancer.gov/statfacts/html/ovary.html
(https://seer.cancer.gov/statfacts/html/ovary.html) . Accessed September
2022.

7.   Pothuri B. BRCA1- and BRCA2-related mutations: therapeutic implications
in ovarian cancer. Ann of Oncol. 2018;24(8):822-827.

8.   Moschetta M, et al.  BRCA somatic mutations and epigenetic BRCA
modifications in serous ovarian cancer. Ann Oncol. 2016 Aug;27(8):1449-55.

9.   Bonadio R, et al. Homologous recombination deficiency in ovarian
cancer: a review of its epidemiology and management. Clinics (Sao Paulo).
2018 Aug 20;73(suppl 1):e450s.

10.  Raja F, et al. Optimal first-line treatment in ovarian cancer. Ann of
Oncol. 2012;23(10):118-127.

11.  NHS Choices, Ovarian Cancer Available
at https://www.nhs.uk/conditions/ovarian-cancer/treatment/
(https://www.nhs.uk/conditions/ovarian-cancer/treatment/) . Accessed
September 2022.

12.  Ledermann J, et al. Newly diagnosed and relapsed epithelial ovarian
carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and
follow-up. Ann Oncol. 2013 Oct;24 Suppl 6:vi24-32.

13.  Moore K, et al. Maintenance Olaparib in Patients with Newly Diagnosed
Advanced Ovarian Cancer. New England Journal of Medicine. 2019;379(26),
pp.2495-2505.

 

 

Adrian Kemp

Company Secretary

AstraZeneca PLC

 

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