REG - AstraZeneca PLC - Lynparza approved in US for BRCAm prostate cancer

AstraZenecaAnnouncement

01/06/2023 07:00

For best results when printing this announcement, please click on link below:
http://newsfile.refinitiv.com/getnewsfile/v1/story?guid=urn:newsml:reuters.com:20230601:nRSA2590Ba&default-theme=true

RNS Number : 2590B  AstraZeneca PLC  01 June 2023

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
(https://www.astrazeneca.com/media-centre/press-releases/2022/lynparza-combo-delays-progression-risk-in-prostate-cancer.html)
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
(https://www.astrazeneca.com/media-centre/press-releases/2020/lynparza-reduced-the-risk-of-death-by-31-percent-in-brca-or-atm-mcrpc-in-profound.html#!)
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
(https://clinicaltrials.gov/ct2/show/NCT03732820) .

 

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 (https://www.astrazeneca.com) and follow the
Company on Twitter @AstraZeneca
(https://twitter.com/AstraZeneca?ref_src=twsrc%5Egoogle%7Ctwcamp%5Eserp%7Ctwgr%5Eauthor)
.

 

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.   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
(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
(https://www.cancer.org/cancer/types/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
(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
(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

 

This information is provided by RNS, the news service of the London Stock Exchange. RNS is approved by the Financial Conduct Authority to act as a Primary Information Provider in the United Kingdom. Terms and conditions relating to the use and distribution of this information may apply. For further information, please contact
rns@lseg.com (mailto:rns@lseg.com)
 or visit
www.rns.com (http://www.rns.com/)
.

RNS may use your IP address to confirm compliance with the terms and conditions, to analyse how you engage with the information contained in this communication, and to share such analysis on an anonymised basis with others as part of our commercial services. For further information about how RNS and the London Stock Exchange use the personal data you provide us, please see our
Privacy Policy (https://www.lseg.com/privacy-and-cookie-policy)
.   END  REAFFFSLEFILVIV