TIDMAZN
RNS Number : 5580Z
AstraZeneca PLC
13 January 2020
13 January 2020 07:00 GMT
Lynparza regulatory submission granted Priority Review in the US
for 1st-line maintenance treatment with bevacizumab in advanced
ovarian cancer
Submission based on Phase III PAOLA-1 trial for patients with
advanced
ovarian cancer regardless of biomarker status or surgical
outcome
AstraZeneca and MSD Inc., Kenilworth, N.J., US (MSD: known as
Merck & Co., Inc. inside the US and Canada) today announced
that a supplemental New Drug Application for Lynparza (olaparib) in
combination with bevacizumab has been accepted and granted Priority
Review in the US for the maintenance treatment of patients with
advanced ovarian cancer who are in complete or partial response to
1st-line platinum-based chemotherapy with bevacizumab.
A Prescription Drug User Fee Act (PDUFA) date is set for the
second quarter of 2020.
The Priority Review by the US Food and Drug Administration (FDA)
was based on results from the pivotal Phase III PAOLA-1 trial,
which were published in The New England Journal of Medicine. The
trial compared Lynparza when added to standard-of-care (SoC)
bevacizumab vs. bevacizumab alone in patients with advanced ovarian
cancer in the 1st-line maintenance setting, regardless of their
biomarker status or outcome from previous surgery.
The investigator-assessed results showed Lynparza added to
bevacizumab reduced the risk of disease progression or death by 41%
based on a hazard ratio of 0.59 (p<0.0001) and improved
progression-free survival (PFS) to a median of 22.1 months vs. 16.6
months for patients treated with bevacizumab alone.
At two years after trial initiation, 46% of patients treated
with Lynparza added to bevacizumab showed no disease progression
vs. 28% of patients treated with bevacizumab alone. The safety and
tolerability profiles of Lynparza and bevacizumab were consistent
with previous trials for each medicine and showed no detriment to
quality of life.
Lynparza is the only PARP inhibitor with two positive randomised
Phase III trials in the 1st-line maintenance setting for advanced
ovarian cancer. It is the only PARP inhibitor approved in the US as
a 1st-line maintenance treatment for patients with BRCA-mutated
advanced ovarian cancer, based on the SOLO-1 trial. If approved,
this would be the fourth indication for ovarian cancer patients in
the US for Lynparza.
Ovarian cancer
Ovarian cancer is the eighth most common cause of death from
cancer in women worldwide. In 2018, there were nearly 300,000 new
cases diagnosed and around 185,000 deaths.(1) Most women are
diagnosed with advanced (Stage III or IV) ovarian cancer and have a
five-year survival rate of approximately 30%.(2) For newly
diagnosed advanced ovarian cancer, the primary aim of treatment is
to delay progression of the disease for as long as possible and
maintain the patient's quality of life with the intent of achieving
complete remission or cure.(3,4,5,6)
PAOLA-1
PAOLA-1 is a double-blind Phase III trial testing the efficacy
and safety of Lynparza added to standard-of-care bevacizumab vs.
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.
Results showed Lynparza added to bevacizumab demonstrated a
statistically significant and clinically meaningful improvement in
PFS, reducing the risk of disease progression or death by 41% and
improving PFS to a median of 22.1 months versus 16.6 months for
those treated with bevacizumab alone (HR 0.59 [95% CI, 0.49-0.72],
p<0.0001). The sensitivity analysis of blinded independent
central review (BICR) of PFS was consistent, showing a similar
improvement with a median of 26.1 months for Lynparza added to
bevacizumab vs. 18.3 months for bevacizumab alone (HR 0.63 [95% CI,
0.51-0.77], p<0.0001).
Overall Grade 3 or above adverse events (AEs) were 57% for
Lynparza added to bevacizumab and 51% for bevacizumab alone. The
most common AEs >=20% were nausea (53%), fatigue (53%),
hypertension (46%), anaemia (41%), lymphopenia (24%), vomiting
(22%) and arthralgia (22%). Grade 3 or above AEs were hypertension
(19%), anaemia (17%), lymphopenia (7%), neutropenia (6%), fatigue
(5%), nausea (2%), diarrhoea (2%), leukopenia (2%) vomiting (1%)
and abdominal pain (1%). AEs led to dose interruption in 54% of
patients on Lynparza added to bevacizumab while 20% of patients
discontinued treatment.
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). ARCAGY-GINECO is an academic group
specialising in clinical and translational research in patients'
cancers and a member of the GCIG (Gynecologic Cancer
InterGroup).
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 homologous recombination
repair, 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 65 countries, including those
in the EU, for the maintenance treatment of platinum-sensitive
relapsed ovarian cancer, regardless of BRCA status. It is approved
in the US, the EU, Japan, China and several other countries as
1st-line maintenance treatment of BRCA-mutated advanced ovarian
cancer following response to platinum-based chemotherapy. It is
also approved in 44 countries, including the US and Japan, for
germline BRCA-mutated, HER2-negative, metastatic breast cancer,
previously treated with chemotherapy; in the EU, this includes
locally advanced breast cancer. It is approved in the US as a
1st-line maintenance treatment for germline BRCA-mutated metastatic
pancreatic cancer. Regulatory reviews are underway in other
jurisdictions for ovarian, breast and pancreatic cancers.
Lynparza, which is being jointly developed and commercialised by
AstraZeneca and MSD, is approved for the treatment of advanced
ovarian cancer, metastatic breast cancer and metastatic pancreatic
cancer and has been used to treat over 30,000 patients worldwide.
Lynparza has the broadest and most advanced clinical-trial
development programme of any PARP inhibitor, 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 potential new
medicine selumetinib, a MEK inhibitor, for multiple cancer types.
Working together, the companies will develop Lynparza and
selumetinib in combination with other potential new medicines and
as monotherapies. Independently, the companies will develop
Lynparza and selumetinib in combination with their respective PD-L1
and PD-1 medicines.
AstraZeneca in oncology
AstraZeneca has a deep-rooted heritage in oncology and offers a
quickly growing portfolio of new medicines that has the potential
to transform patients' lives and the Company's future. With at
least six new medicines to be launched between 2014 and 2020, and a
broad pipeline of small molecules and biologics in development, the
Company is committed to advance oncology as a key growth driver for
AstraZeneca focused on lung, ovarian, breast and blood cancers. In
addition to AstraZeneca's main capabilities, the Company is
actively pursuing innovative partnerships and investment that
accelerate the delivery of our strategy, as illustrated by the
investment in Acerta Pharma in haematology.
By harnessing the power of four scientific platforms -
Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response
and Antibody Drug Conjugates - 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/NYSE: 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 and Metabolism, and Respiratory.
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.
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References
1. The World Health Organization. IARC. Globocan 2018. Available
at: www.gco.iarc.fr/ [Accessed December 2019].
2. National Cancer Institute. (2019). Cancer Stat Facts: Ovarian Cancer Available at: https://seer.cancer.gov/statfacts/html/ovary.html [Accessed December 2019].
3. Moore K et al. Maintenance Olaparib in Patients with Newly
Diagnosed Advanced Ovarian Cancer. Presented at ESMO October
2018.
4. Raja, F. A., Chopra, N. & Ledermann, J. A. 2012. Optimal
first-line treatment in ovarian cancer. Annals of Oncology.
Official Journal of the European Society for Medical Oncology. 23
Suppl 10, x118-127.
5. NHS Choices. Ovarian Cancer. Available at:
https://www.nhs.uk/conditions/ovarian-cancer/treatment/ [Accessed
December 2019].
6. Ledermann.et al. 2013. Newly diagnosed and relapsed
epithelial ovarian carcinoma: ESMO Clinical Practice for diagnosis,
treatment and follow-up. Annals of Oncology, 24(suppl 6),
pp.vi24-vi32.
Adrian Kemp
Company Secretary
AstraZeneca PLC
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END
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