AstraZeneca and MSD?s Lynparza is the only PARP inhibitor to demonstrate an improvement in progression-free survival for patients in this setting

AstraZeneca and MSD Inc., Kenilworth, N.J., US (MSD: known as Merck & Co., Inc. inside the US and Canada) today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has adopted a positive opinion, recommending?Lynparza?(olaparib) as a 1st-line maintenance treatment of?BRCA-mutated advanced ovarian cancer. The recommendation is for the use of?Lynparza?tablets as a maintenance treatment of adult patients with advanced (FIGO stages III and IV)?BRCA1/2-mutated (germline and/or somatic) high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) following completion of first-line platinum-based chemotherapy. Dave Fredrickson, Executive Vice President, Oncology, said: ?There remains a significant unmet need in the treatment of advanced ovarian cancer as 70% of women globally relapse within the first three years after their initial treatment. The results of SOLO-1 demonstrate the potential of using?Lynparza?earlier in the treatment pathway as a maintenance therapy, and reinforce the importance of identifying a patient?s?BRCA?mutation status as soon as they are diagnosed.? Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, MSD Research Laboratories, said: ?Women with advanced ovarian cancer need and deserve new treatment options. In the SOLO-1 trial,?Lynparza?demonstrated a significant progression-free survival benefit as maintenance treatment for patients with advanced?BRCA-mutated ovarian cancer following response to first-line platinum-based chemotherapy. If approved, this expanded indication could change the way women in Europe with?BRCA-mutated advanced ovarian cancer are treated.? The positive opinion is based on data from the pivotal Phase?III?SOLO-1 trial which?showed that?Lynparza?reduced the risk of disease progression or death by 70% vs. placebo following response to platinum-based chemotherapy (HR 0.30 [95% CI 0.23-0.41], p<0.001). Of those patients receiving?Lynparza, 60.4% remained progression-free at 36 months vs. 26.9% of women in the placebo arm. Lynparza?is currently approved in 64 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 as 1st-line maintenance treatment of?BRCAm advanced ovarian cancer following response to platinum-based chemotherapy. It is also approved in 38 countries, including the US, countries in the EU and Japan, for germline?BRCAm HER2-negative metastatic breast cancer previously treated with chemotherapy; in the EU this includes locally advanced breast cancer. Regulatory reviews are underway in other jurisdictions for both ovarian cancer and breast cancer. About SOLO-1 SOLO-1 was a Phase III randomised, double-blinded, placebo-controlled, multicentre trial to evaluate the efficacy and safety of?Lynparza?tablets (300mg twice daily) as maintenance monotherapy compared with placebo, in patients with?BRCAm advanced ovarian cancer following 1st-line platinum-based chemotherapy. The trial randomised 391 patients with a deleterious or suspected deleterious germline or somatic?BRCA1 or?BRCA2 mutation who were in complete or partial clinical response following platinum-based chemotherapy. Patients were randomised (2:1) to receive?Lynparza?or placebo for up to two years or until disease progression. Patients who had a partial response at two years were permitted to stay on therapy at the investigator?s discretion. The primary endpoint was progression-free survival (PFS) and key secondary endpoints included time to second disease progression or death, time to first subsequent treatment and overall survival. The data were presented on 21 October 2018 at the Presidential Symposium of the ESMO 2018 Congress in Munich, Germany and published simultaneously online in the?New England Journal of Medicine. Summary of PFS^i,ii

	Lynparza?(n=260)	Placebo (n=131)
Number of patients with event (%)iii	102 (39)	96 (73)
Median PFS (in months)	Not reached	13.8
Hazard ratio (95% CI)	0.30 (0.23-0.41)
P-value	p<0.001

^{i Investigator-assessed ii Median (interquartile range) duration of follow-up 40.7 months (34.9?42.9) for?Lynparza?and 41.2 months (32.2?41.6) for placebo iii Analysis was done at 50.6% maturity} The SOLO-1 safety profile was in line with that observed in prior clinical trials. The most common adverse events (AEs) = 20% were nausea (77%), fatigue (63%), vomiting (40%), anaemia (39%) and diarrhoea (34%). The most common = Grade 3 AEs were anaemia (22%) and neutropenia (9%). Some 71% of patients on?Lynparza?remained on the recommended starting dose. Additionally, 88% of patients on?Lynparza?continued treatment without an AE-related discontinuation. About ovarian cancer Ovarian cancer is a leading cause of cancer death in women worldwide, with a five-year survival rate of 19%.¹?In 2018, there were over 295,000 new cases diagnosed and around 185,000 deaths.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 About?BRCA?mutations Breast cancer susceptibility genes 1/2 (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. About?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 (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 tumour types with defects and dependencies in the DDR. Lynparza, which is being jointly developed and commercialised by AstraZeneca and MSD, is approved for advanced ovarian cancer and metastatic breast cancer and has been used in over 20,000 patients worldwide. On 26 February 2019, AstraZeneca and MSD?announced?that?Lynparza?became the first PARP inhibitor to demonstrate benefit in germline?BRCAm metastatic pancreatic cancer in the Phase III POLO trial. 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. About the AstraZeneca and MSD strategic oncology collaboration In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US, known as MSD outside the United States 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. About 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, we are committed to advance Oncology as one of AstraZeneca?s four Growth Platforms focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by our 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. About AstraZeneca AstraZeneca 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. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit?astrazeneca.com?and follow us on Twitter?@AstraZeneca.

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References

1. American Cancer Society. Survival Rates for Ovarian Cancer, by Stage. Available at:?https://www.cancer.org/cancer/ovarian-cancer/detection-diagnosis-staging/survival-rates.html. Accessed: March 2019 2. Globocan 2018?http://gco.iarc.fr/ 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. Optimal first-line treatment in ovarian cancer. Ann. Oncol. Off. J. Eur. Soc. Med. Oncol. 23 Suppl 10, x118-127 (2012) 5. NHS Choices, Ovarian Cancer Accessed?https://www.nhs.uk/conditions/ovarian-cancer/treatment/?in September 2018 6. Ledermann.et al. 2013. Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice