KENILWORTH - AstraZeneca and Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that LYNPARZA has been approved in the European Union (EU) as a monotherapy for the maintenance treatment of adult patients with germline BRCA1/2 mutations who have metastatic adenocarcinoma of the pancreas and have not progressed after a minimum of 16 weeks of platinum treatment within a first-line chemotherapy regimen.
The approval by the European Commission (EC) was based on results from the Phase 3 POLO trial, which were published in The New England Journal of Medicine. It follows the recommendation for approval by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA).
Pancreatic cancer is a rare, life-threatening disease with the lowest survival rate of the most common cancers. Approximately 5-7% of patients with metastatic pancreatic cancer have a germline BRCA mutation.
Dr. Hedy L. Kindler, co-principal investigator of the POLO trial and professor of medicine, University of Chicago Medicine, said, 'Today's approval opens the door to a new era of biomarker-led care for patients with metastatic pancreatic cancer in the EU, which has the highest incidence of any region globally. LYNPARZA now provides clinicians with a targeted, well-tolerated treatment option for patients with germline BRCA-mutated metastatic pancreatic cancer.'
Dave Fredrickson, executive vice president, oncology business unit, AstraZeneca, said, 'Patients with metastatic pancreatic cancer historically have faced poor outcomes due to the aggressive nature of the disease and few treatment advances have been made over the last few decades. In the POLO trial, LYNPARZA nearly doubled median progression-free survival versus placebo after first-line chemotherapy for patients with germline BRCA-mutated metastatic pancreatic cancer. This approval underscores the importance of testing all patients for germline BRCAmutations at the time of diagnosis to help inform personalized treatment options for patients in the EU.'
Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories, said, 'Merck and AstraZeneca are committed to advancing research into the treatment of patients with challenging types of cancer, including those with metastatic pancreatic cancer. LYNPARZA is now the only approved PARP inhibitor in biomarker-selected patients with metastatic pancreatic cancer. We look forward to making this targeted treatment option available for patients across the EU as quickly as possible.'
The POLO trial demonstrated that LYNPARZA nearly doubled the time patients with germline BRCA-mutated (gBRCAm) metastatic pancreatic cancer lived without disease progression or death to a median of 7.4 months versus 3.8 months on placebo (HR 0.53 [95% CI 0.35-0.81] p=0.0035).
The safety and tolerability profile of LYNPARZA in the POLO trial was consistent with previous trials. The most common adverse reactions (ARs) 10% were fatigue/asthenia (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%). The most common Grade 3 ARs were anemia (11%), fatigue/asthenia (5%), decreased appetite (3%), abdominal pain (2%), vomiting (1%) and arthralgia (1%). Among patients taking LYNPARZA, dose interruptions due to an AR of any grade occurred in 35% and dose reductions due to an AR occurred in 17%. Discontinuation due to ARs occurred in 6% of patients receiving LYNPARZA.
LYNPARZA is approved in the U.S. and several other countries as a first-line maintenance treatment for patients with gBRCAm metastatic pancreatic cancer whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen, based on the Phase 3 POLO trial, with ongoing regulatory reviews in other jurisdictions.
About POLO
POLO is a Phase 3 randomized, double-blinded, placebo-controlled, multi-center trial of LYNPARZA tablets (300 mg twice daily) as maintenance monotherapy versus placebo. The trial randomized 154 patients with gBRCAm metastatic pancreatic cancer whose disease had not progressed on first-line platinum-based chemotherapy. Patients were randomized (3:2) to receive LYNPARZA or placebo until disease progression. The primary endpoint was progression-free survival and key secondary endpoints included overall survival, time to second disease progression, overall response rate and health-related quality of life.
About LYNPARZA (olaparib)
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.
LYNPARZA, which is being jointly developed and commercialized by AstraZeneca and Merck, has a broad and advanced clinical trial development program, and AstraZeneca and Merck are working together to understand how it may affect multiple PARP-dependent tumors as a monotherapy and in combination across multiple cancer types.
About Pancreatic Cancer
Pancreatic cancer has a high unmet medical need. The disease has the lowest survival rate of the most common cancers. Globally, pancreatic cancer is the 12th-most commonly occurring cancer and the 7th leading cause of cancer death. There were approximately 460,000 new cases worldwide in 2018. As there are often no symptoms, or symptoms may be non-specific in the early stages, around 80% of pancreatic cancer patients are diagnosed when the disease has metastasized. Despite advances in treatment, few improvements have been made in diagnosis and treatment in the past few decades. Current treatment is surgery (for which approximately only 10-20% of patients are eligible), chemotherapy and radiotherapy, highlighting a critical unmet medical need for more treatment options.
AboutBRCAMutations
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 in 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 the AstraZeneca and Merck Strategic Oncology Collaboration
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 certain oncology products including 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.
Merck's Focus on Cancer
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.
About Merck
For more than 125 years, Merck, known as MSD outside of 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.
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