In the key secondary endpoint of OS, LYNPARZA reduced the risk of death by 32% (HR=0.68 [98.5% CI, 0.47-0.97]; p=0.009) versus placebo. The three-year survival rate was 92.8% (95% CI, 90.8-94.4) versus 89.1% (95% CI, 86.7-91) for those on placebo. At four years, the survival rate was 89.8% (95% CI, 87.2-91.9) for patients treated with LYNPARZA versus 86.4% (95% CI, 83.6-88.7) for those on placebo. The analyses at three and four years are based on Kaplan-Meier estimates and are descriptive only. The OlympiA study was not powered to assess a statistical difference between treatment groups at these timepoints.

The safety and tolerability profile of LYNPARZA in this trial was in line with that observed in prior clinical trials. The most common adverse reactions (ARs) ≥10% for LYNPARZA were nausea (57%), fatigue (42%), anemia (24%), vomiting (23%), headache (20%), diarrhea (18%), leukopenia (17%), neutropenia (16%), decreased appetite (13%), dysgeusia (12%), dizziness (11%) and stomatitis (10%). Approximately 10% of patients treated with LYNPARZA discontinued treatment due to an AR. The most common Grade ≥3 ARs for LYNPARZA were anemia (9%), neutropenia (5%), leukopenia (3%) and fatigue (1.8%).

Professor Andrew Tutt, global chair of the OlympiA trial and professor of oncology, The Institute of Cancer Research, London, and King's College London, said, "OlympiA's latest results are great news for patients with a specific inherited form of breast cancer. Most breast cancers are identified in the early stages and many patients will do very well, but for those with higher risk disease at diagnosis, the risk of cancer returning can be unacceptably high. OlympiA has now shown that olaparib not only reduced the risk of recurrence, but also improved overall survival for women with high risk early-stage breast cancer and a BRCA1/2 mutation and is an exciting demonstration of the benefits of targeting the specific biology of disease for these women."

Susan Galbraith, executive vice president, oncology R&D, AstraZeneca, said, "These exciting results further support how LYNPARZA could significantly change the way people with germline BRCA-mutated early breast cancer are treated. The OlympiA trial is also the first time we've seen a PARP inhibitor deliver survival benefit in early breast cancer, highlighting the importance of persistent innovation in tackling cancer early."

Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories, said, "The results from the OlympiA trial highlight that patients with germline BRCA-mutated, HER2-negative high-risk early breast cancer can both live longer and with reduced risk of disease recurrence when treated with LYNPARZA in the adjuvant setting compared to placebo. These data further reinforce the importance of germline BRCA testing immediately after diagnosis to help identify patients who may be eligible for treatment with LYNPARZA."

Primary results from the Phase 3 OlympiA trial were first presented during the 2021 American Society of Clinical Oncology Annual Meeting and are published in The New England Journal of Medicine. In OlympiA, LYNPARZA demonstrated a statistically significant improvement in the primary endpoint of invasive disease-free survival (IDFS), reducing the risk of invasive breast cancer recurrences, second cancers or death by 42% (HR=0.58 [99.5% CI, 0.41-0.82]; p<0.0001) versus placebo.

Last week, LYNPARZA was approved by the U.S. Food and Drug Administration for the adjuvant treatment of patients with gBRCAm, HER2-negative high-risk early breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy based on results from the OlympiA trial. LYNPARZA is also approved in the U.S., EU, Japan and several other countries for the treatment of patients with gBRCAm, HER2-negative metastatic breast cancer previously treated with chemotherapy and, if hormone receptor-positive, endocrine therapy if appropriate based on results from the Phase 3 OlympiAD trial. In the EU and Japan, this indication also includes patients with locally advanced breast cancer.

OlympiA is a Phase 3, double-blind, parallel group, placebo-controlled, international trial evaluating the efficacy and safety of LYNPARZA versus placebo as adjuvant treatment in patients with gBRCAm, HER2-negative high-risk early breast cancer who have completed definitive local treatment and neoadjuvant or adjuvant chemotherapy. The primary endpoint was IDFS, defined as the time from randomization to the date of the first loco-regional or distant recurrence or new cancer or death from any cause. A key secondary efficacy outcome measure was OS.

Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): Occurred in approximately 1.5% of patients exposed to LYNPARZA monotherapy, and the majority of events had a fatal outcome. The median duration of therapy in patients who developed MDS/AML was 2 years (range: <6 months to >10 years). All of these patients had previous chemotherapy with platinum agents and/or other DNA-damaging agents, including radiotherapy.

Venous Thromboembolic Events: Including pulmonary embolism, occurred in 7% of patients with metastatic castration-resistant prostate cancer who received LYNPARZA plus androgen deprivation therapy (ADT) compared to 3.1% of patients receiving enzalutamide or abiraterone plus ADT in the PROfound study. Patients receiving LYNPARZA and ADT had a 6% incidence of pulmonary embolism compared to 0.8% of patients treated with ADT plus either enzalutamide or abiraterone. Monitor patients for signs and symptoms of venous thrombosis and pulmonary embolism, and treat as medically appropriate, which may include long-term anticoagulation as clinically indicated.

Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA in the first-line maintenance setting for SOLO-1 were: nausea (77%), fatigue (67%), abdominal pain (45%), vomiting (40%), anemia (38%), diarrhea (37%), constipation (28%), upper respiratory tract infection/influenza/nasopharyngitis/bronchitis (28%), dysgeusia (26%), decreased appetite (20%), dizziness (20%), neutropenia (17%), dyspepsia (17%), dyspnea (15%), leukopenia (13%), urinary tract infection (13%), thrombocytopenia (11%), and stomatitis (11%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the first-line maintenance setting for SOLO-1 were: decrease in hemoglobin (87%), increase in mean corpuscular volume (87%), decrease in leukocytes (70%), decrease in lymphocytes (67%), decrease in absolute neutrophil count (51%), decrease in platelets (35%), and increase in serum creatinine (34%).

Most common adverse reactions (Grades 1-4) in ≥10% of patients treated with LYNPARZA/bevacizumab compared to a ≥5% frequency for placebo/bevacizumab in the first-line maintenance setting for PAOLA-1 were: nausea (53%), fatigue (including asthenia) (53%), anemia (41%), lymphopenia (24%), vomiting (22%) and leukopenia (18%). In addition, the most common adverse reactions (≥10%) for patients receiving LYNPARZA/bevacizumab irrespective of the frequency compared with the placebo/bevacizumab arm were: diarrhea (18%), neutropenia (18%), urinary tract infection (15%) and headache (14%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients for LYNPARZA in combination with bevacizumab in the first-line maintenance setting for PAOLA-1 were: decrease in hemoglobin (79%), decrease in lymphocytes (63%), increase in serum creatinine (61%), decrease in leukocytes (59%), decrease in absolute neutrophil count (35%) and decrease in platelets (35%).

Most common adverse reactions (Grades 1-4) in ≥20% of patients who received LYNPARZA in the maintenance setting for SOLO-2 were: nausea (76%), fatigue (including asthenia) (66%), anemia (44%), vomiting (37%), nasopharyngitis/upper respiratory tract infection (URI)/influenza (36%), diarrhea (33%), arthralgia/myalgia (30%), dysgeusia (27%), headache (26%), decreased appetite (22%), and stomatitis (20%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the maintenance setting (SOLO-2/Study 19) were: increase in mean corpuscular volume (89%/82%), decrease in hemoglobin (83%/82%), decrease in leukocytes (69%/58%), decrease in lymphocytes (67%/52%), decrease in absolute neutrophil count (51%/47%), increase in serum creatinine (44%/45%), and decrease in platelets (42%/36%).

Most common adverse reactions (Grades 1-4) in ≥20% of patients who received LYNPARZA for advanced gBRCAm ovarian cancer after 3 or more lines of chemotherapy (pooled from 6 studies) were: fatigue/asthenia (66%), nausea (64%), vomiting (43%), anemia (34%), diarrhea (31%), nasopharyngitis/upper respiratory tract infection (URI) (26%), dyspepsia (25%), myalgia (22%), decreased appetite (22%), and arthralgia/musculoskeletal pain (21%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA for advanced gBRCAm ovarian cancer (pooled from 6 studies) were: decrease in hemoglobin (90%), mean corpuscular volume elevation (57%), decrease in lymphocytes (56%), increase in serum creatinine (30%), decrease in platelets (30%), and decrease in absolute neutrophil count (25%).

Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA in the adjuvant setting for OlympiA were: nausea (57%), fatigue (including asthenia) (42%), anemia (24%), vomiting (23%), headache (20%), diarrhea (18%), leukopenia (17%), neutropenia (16%), decreased appetite (13%), dysgeusia (12%), dizziness (11%), and stomatitis (10%).

Most common laboratory abnormalities (Grades 1-4) in >25% of patients who received LYNPARZA in the metastatic setting for OlympiAD were: decrease in hemoglobin (82%), decrease in lymphocytes (73%), decrease in leukocytes (71%), increase in mean corpuscular volume (71%), decrease in absolute neutrophil count (46%), and decrease in platelets (33%).

Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA in the first-line maintenance setting for POLO were: fatigue (60%), nausea (45%), abdominal pain (34%), diarrhea (29%), anemia (27%), decreased appetite (25%), constipation (23%), vomiting (20%), back pain (19%), arthralgia (15%), rash (15%), thrombocytopenia (14%), dyspnea (13%), neutropenia (12%), nasopharyngitis (12%), dysgeusia (11%), and stomatitis (10%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the first-line maintenance setting for POLO were: increase in serum creatinine (99%), decrease in hemoglobin (86%), increase in mean corpuscular volume (71%), decrease in lymphocytes (61%), decrease in platelets (56%), decrease in leukocytes (50%), and decrease in absolute neutrophil count (25%).

For the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

For the treatment of adult patients with deleterious or suspected deleterious gBRCAm, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer, who have been treated with chemotherapy in the neoadjuvant, adjuvant or metastatic setting. Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

Please see complete Prescribing Information, including Medication Guide.

LYNPARZA is a first-in-class PARP inhibitor and the first targeted treatment to potentially exploit DNA damage response (DDR) pathway deficiencies, such as BRCA mutations, to preferentially kill cancer cells. 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 tumor types with defects and dependencies in the DDR.

Early breast cancer is defined as disease confined to the breast with or without regional lymph node involvement and the absence of distant metastatic disease. For women in the U.S., the five-year survival rate is 99% for localized breast cancer (cancer that is found only in the breast area) and 86% for regional breast cancer (cancer that has spread outside the breast to nearby structures or lymph nodes). Breast cancer is one of the most biologically diverse tumor types with various factors fueling its development and progression. The discovery of biomarkers in the development of breast cancer has greatly impacted scientific understanding of the disease.

BRCA1 and BRCA2 (breast cancer susceptibility genes 1/2) 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.

In July 2017, AstraZeneca and Merck, known as MSD outside the United States and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialize LYNPARZA, the world's first PARP inhibitor, for multiple cancer types. Working together, the companies will develop these products in combination with other potential new medicines and as monotherapies. Independently, the companies will develop these oncology products in combination with their respective PD-L1 and PD-1 medicines.

Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

For over 130 years, Merck, known as MSD outside the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the world's most challenging diseases in pursuit of our mission to save and improve lives. We demonstrate our commitment to patients and population health by increasing access to health care through far-reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of research to prevent and treat diseases that threaten people and animals – including cancer, infectious diseases such as HIV and Ebola, and emerging animal diseases – as we aspire to be the premier research-intensive biopharmaceutical company in the world. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.

This news release of Merck & Co., Inc., Kenilworth, N.J., USA (the "company") includes "forward-looking statements" within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company's management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

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