RAHWAY - AstraZeneca and Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced that LYNPARZA has been approved in China as first-line maintenance treatment for adult patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy in combination with bevacizumab and whose cancer is associated with homologous recombination deficiency (HRD)-positive status.
In China, ovarian cancer is the third most common gynecologic cancer, and the five-year survival rate is approximately 39%, with more than 70% of women diagnosed with advanced disease (stage III or IV). In 2020, there were over 55,000 new cases of ovarian cancer diagnosed in China.
The approval by China's National Medical Products Administration was based on an HRD-positive subgroup exploratory analysis of the Phase 3 PAOLA-1 trial, which showed LYNPARZAplus bevacizumab following response to platinum-based chemotherapy demonstrated a substantial progression-free survival (PFS) improvement versus bevacizumab alone for patients with HRD-positive advanced ovarian cancer. The safety and tolerability profile of LYNPARZA in this trial was in line with that observed in prior clinical trials, with no new safety signals. The most common adverse reactions (ARs) occurring in 10% of patients treated with LYNPARZA in combination with bevacizumab and at a 5% greater frequency compared to bevacizumab alone were nausea (53%), fatigue (including asthenia) (53%), anemia (41%), lymphopenia (24%), vomiting (22%) and leukopenia (18%). Additional ARs that occurred in 10% of patients receiving LYNPARZA in combination with bevacizumab, irrespective of the frequency compared to bevacizumab alone were diarrhea (18%), neutropenia (18%), urinary tract infection (15%) and headache (14%).
During the European Society for Medical Oncology (ESMO) Congress 2022, updated results were presented from the PAOLA-1 trial, demonstrating that LYNPARZAplus bevacizumab provided a clinically meaningful improvement in overall survival (OS) in an exploratory subgroup analysis of HRD-positive patients with advanced ovarian cancer. These OS results were not statistically significant.
Professor Ding Ma, member of the Chinese Academy of Engineering, said, 'Ovarian cancer has the highest fatality rate among gynecologic cancers in China. The emergence of PARP inhibitors and their application in the first-line treatment of ovarian cancer could help patients delay disease progression and achieve long-term remission. In the PAOLA-1 trial, the combination of olaparib and bevacizumab demonstrated clinically meaningful improvements in overall survival. This approval provides HRD-positive patients with a new option for first-line maintenance therapy.'
Professor Beihua Kong, chairman of the gynecological oncology branch of the Chinese Medical Association, said, 'Ovarian cancer has entered the era of precision medicine, and HRD detection (including BRCA1/2 mutations) has important clinical value for newly diagnosed patients with advanced ovarian cancer to help guide first-line treatment decisions. The approval of the combination of olaparib and bevacizumab brings a clinically meaningful survival benefit to HRD-positive patients, and further reflects the importance of a precision approach to help guide treatment decisions in ovarian cancer.'
Dave Fredrickson, executive vice president, oncology business unit, AstraZeneca, said, 'The maintenance treatment of LYNPARZAin combination with bevacizumab has shown to both improve progression-free survival and provide a clinically meaningful improvement in overall survival in patients with HRD-positive advanced ovarian cancer following response to platinum-based chemotherapy. I am thrilled we can now bring this targeted treatment option to these patients in China.'
Dr. Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories, said, 'This approval is an important milestone for patients with newly diagnosed advanced ovarian cancer in China and underscores the critical importance of HRD testing for all women with advanced ovarian cancer at the point of diagnosis.'
The primary results from the PAOLA-1 trial showed that LYNPARZAplus bevacizumabreduced the risk of disease progression or death by 67% (HR=0.33 [95% CI, 0.25-0.45]). In the subgroup of patients with HRD-positive advanced ovarian cancer, the addition of LYNPARZAto bevacizumab improved PFS to a median of 37.2 versus 17.7 months with bevacizumab alone. The data from the PAOLA-1 trial were published in The New England Journal of Medicine in 2019.
Further results from the five-year analysis of the PAOLA-1 trial recently presented at the ESMO Congress 2022 showed LYNPARZA plus bevacizumab increased median OS to 56.5 months versus 51.6 months with bevacizumab alone in patients with newly diagnosed advanced ovarian cancer. This increase was not statistically significant. In an exploratory subgroup analysis of HRD-positive patients, LYNPARZAplus bevacizumab provided a clinically meaningful improvement in OS, reducing the risk of death by 38% (HR=0.62 [95% CI, 0.45-0.85]) versus bevacizumab, despite PAOLA-1 having 30% stage IV patients.
LYNPARZA in combination with bevacizumab is approved in the U.S., European Union and several other countries as a first-line maintenance treatment for patients with HRD-positive advanced ovarian cancer and is currently under regulatory review in other countries around the world.
About PAOLA-1
PAOLA-1 is a Phase 3, double-blind trial evaluating the efficacy and safety of LYNPARZAadded to standard-of-care bevacizumab versus bevacizumab alone as a first-line maintenance treatment for patients with newly diagnosed advanced FIGO stage III-IV high-grade serous or endometroid ovarian, fallopian tube or peritoneal cancer who had a complete or partial response to first-line treatment with platinum-based chemotherapy and bevacizumab. AstraZeneca and Merck announced in August 2019 that the trial met its primary endpoint of PFS in the overall trial population.
PAOLA-1 is an ENGOT (European Network of Gynaecological Oncological Trial groups) trial, sponsored by ARCAGY Research (Association de Recherche sur les CAncers dont GYnecologiques) on behalf of GINECO (Groupe d'Investigateurs National des Etudes des Cancers Ovariens et du sein). ARCAGY-GINECO is an academic group specializing in clinical and translational research in patients' cancers and a member of the GCIG (Gynecologic Cancer InterGroup).
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 ovarian cancer
Ovarian cancer is the eighth most common cancer in women worldwide. Globally, there were more than 313,000 new cases of ovarian cancer in 2020 and over 207,000 deaths. The five-year survival rate of newly diagnosed advanced ovarian cancer patients has typically been 30-50%. Roughly half of women with advanced ovarian cancer have HRD-positive tumors, including those with a BRCA mutation, and one in four women have a BRCA mutation. The primary aim of first-line treatment is to delay disease progression for as long as possible with the intent to achieve long-term remission.
About homologous recombination deficiency
Homologous recombination deficiency, which defines a subgroup of ovarian cancer, encompasses a wide range of genetic abnormalities, including BRCA mutations and beyond. As with BRCA gene mutations, HRD interferes with normal cell DNA repair mechanisms and confers sensitivity to PARP inhibitors including LYNPARZA.
About the AstraZeneca and Merck strategic oncology collaboration
In July 2017, AstraZeneca and Merck, known as MSD outside of 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
At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world - and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities.
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