Lynparza (Olaparib) in Combination with Bevacizumab Approved in China for First-Line Maintenance Treatment of HRD-Positive Advanced Ovarian Cancer

PAOLA-1 IIILong-term follow-up results of the Phase trial demonstrate clinical survival benefits

ShanghaiSeptember 22, 2022PR Newswire -- Today, AstraZeneca and MSD jointly announced that the China National Medical Products Administration has officially approved their PARP inhibitor, Lynparza.^®(English brand name: Lynparza, generic name: Olaparib Tablets) New indication: Olaparib in combination with Bevacizumab is indicated for the maintenance treatment of adult patients with homologous recombination repair deficiency (HRD)-positive advanced epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer who have achieved complete or partial response after first-line platinum-based chemotherapy in combination with Bevacizumab. Under the policy support that encourages pharmaceutical innovation and accelerates the approval of clinically urgent new drugs, Olaparib has once again been approved in China for a new indication as first-line maintenance treatment for advanced ovarian cancer.

This approval was based on the results of the pivotal Phase III PAOLA-1 trial. PAOLA-1 met its primary endpoint; in the ITT population, the risk of progression or death was reduced by 41% (HR 0.59; 95% CI 0.49-0.72; p<0.0001) in the olaparib/bevacizumab group compared to the placebo/bevacizumab group. In the HRD-positive population, the median PFS was extended by nearly 20 months in the olaparib/bevacizumab group compared to the placebo/bevacizumab group (median PFS 37.2 vs 17.7 months), with a 67% reduction in the risk of progression or death (HR 0.33; 95% CI 0.25-0.45). The latest overall survival (OS) follow-up data were presented at the 2022 European Society for Medical Oncology (ESMO) Congress: despite approximately 50% of patients in the placebo plus bevacizumab group receiving PARP inhibitor therapy after disease progression, maintenance treatment with olaparib plus bevacizumab still provided clinically meaningful OS improvement in HRD-positive patients, with a 5-year survival rate as high as 65.5%, an increase of 17% in the 5-year OS rate compared to the placebo plus bevacizumab group, and a 38% reduction in the risk of death (HR 0.62; 95% CI 0.45-0.85).

Academician Ding Ma of the Chinese Academy of Engineering stated: "Ovarian cancer has the highest mortality rate among gynecological malignant tumors in China. The emergence of PARP inhibitors and their application in first-line maintenance treatment for ovarian cancer have brought new hope for delaying recurrence, extending patient survival, and increasing the possibility of a cure. In the PAOLA-1 clinical trial, the combination of Olaparib and Bevacizumab provided clinically meaningful overall survival (OS) improvement for HRD-positive patients, offering a new option for first-line maintenance therapy."

Professor Kong Beihua, Chairman of the Gynecologic Oncology Branch of the Chinese Medical Association, stated: "Ovarian cancer has entered the era of precision treatment. HRD testing (including BRCA1/2 mutations) holds significant clinical value for newly diagnosed advanced ovarian cancer patients, providing a basis for selecting subsequent treatment plans and predicting prognosis. The approval and market launch of the Olaparib and Bevacizumab combination regimen brings clear survival benefits to HRD-positive patients and further highlights the importance of precision diagnosis and treatment in the field of ovarian cancer."

Mr. Leon Wang, Executive Vice President of AstraZeneca Global, President of International Business and China, stated: "As the first PARP inhibitor approved in China, Olaparib has ushered in a new era of targeted treatment for advanced ovarian cancer. The approval today further expands the beneficiary population for its first-line maintenance therapy indication, marking another milestone for Olaparib in the field of ovarian cancer treatment in China. This fully demonstrates AstraZeneca's commitment to the value of 'patient-centricity,' continuously bringing high-quality innovative drugs to more patients. In the future, we will continue to collaborate with government and industry partners to explore comprehensive patient management solutions and help improve the diagnosis and treatment of gynecological cancers in Chinese women."

MSD Global Senior Vice President and MSD China President, Anna Tian, stated: "We are very pleased to see that since its initial approval in 2018, Olaparib has been approved for four indications in China, three of which, including the newly approved indication, are for the treatment of advanced ovarian cancer patients. Women's health is closely related to the stability of their families and even society. We will continue to collaborate with all parties, including industry partners, to improve the accessibility of innovative drugs, creating an era where cancer can be treated and potentially cured, jointly safeguarding the health of countless women in China."

Olaparib is an important outcome of the strategic cooperation in innovative oncology drugs between AstraZeneca and MSD. Olaparib was first approved in China in August 2018 for the maintenance treatment of patients with platinum-sensitive recurrent ovarian cancer, and was again approved in China in December 2019 for first-line maintenance treatment of BRCA-mutated advanced ovarian cancer. In June 2021, Olaparib received its first approval in China for prostate cancer, indicated for the treatment of adult patients with metastatic castration-resistant prostate cancer carrying germline or somatic BRCA mutations who have failed prior treatment.

About Ovarian Cancer

Ovarian cancer is the eighth most common cancer among women globally^[1]According to statistics, there were 55,342 new cases of ovarian cancer in China in 2020, with 37,519 deaths.^[2]Over the past decade, the incidence of ovarian cancer in China has increased by 30%, and the mortality rate has risen by 18%. Among gynecological malignancies, the incidence of ovarian cancer ranks third after cervical cancer and endometrial cancer, but it has the lowest three-year survival rate, which is only 39%.^[3], with the highest recurrence rate of 70% within 5 years.^[4]The main purpose of first-line treatment is to delay disease progression as much as possible in order to achieve long-term remission.^[5-7]。

AboutPAOLA-1

PAOLA-1 is a randomized, double-blind, placebo-controlled, multicenter pivotal Phase III study sponsored by ARCAGY Research on behalf of the European Network of Gynaecological Oncology Trial Groups (ENGOT) and the Gynecologic Cancer InterGroup (GCIG). The study aims to evaluate the efficacy and safety of olaparib in combination with bevacizumab as first-line maintenance therapy compared to placebo in newly diagnosed advanced (FIGO Stage III-IV) high-grade serous or endometrioid ovarian cancer, fallopian tube cancer, or primary peritoneal cancer patients who achieved remission after first-line platinum-based chemotherapy combined with bevacizumab. In August 2019, AstraZeneca and MSD announced that the trial met the primary endpoint of PFS across the overall study population.

About Olaparib

Olaparib is the world's first PARP inhibitor and also the first to block homologous recombination repair (HRR) defects (e.g.BRCA1 and/orBRCA2 mutations, or defects caused by other drugs (such as novel endocrine therapies), in cells/tumors with targeted therapeutic agents for the DNA Damage Repair (DDR) pathway.

Inhibition of PARP protein by Olaparib can lead to the trapping of PARP bound to DNA single-strand breaks, replication fork stalling, collapse, and the generation of DNA double-strand breaks, resulting in tumor cell death.

Olaparib is currently approved in multiple countries, covering various types of tumors, including maintenance treatment for platinum-sensitive recurrent ovarian cancer, as well as monotherapy or in combination with bevacizumab for first-line maintenance therapy.BRCAMutation（BRCAm）Or homologous recombination repair deficiency (HRD) positive advanced ovarian cancer.

Olaparib, jointly developed and commercialized by AstraZeneca and MSD, is a cornerstone drug in AstraZeneca's industry-leading portfolio of potential new drugs targeting the DDR mechanism in cancer cells.

Regarding the Oncology Strategic Collaboration Between AstraZeneca and MSD

In July 2017, AstraZeneca and MSD (MSD is the corporate name of Merck & Co., Inc. in Kenilworth, New Jersey, USA) announced a global strategic collaboration in the field of oncology to jointly conduct clinical development and commercial promotion of the world's first PARP inhibitor, olaparib, and the promising new MEK inhibitor, selumetinib, for multiple cancer indications.

About AstraZeneca

AstraZeneca (LSE/STO/Nasdaq: AZN) is a science-led global biopharmaceutical business focused on the discovery, development, and commercialization of prescription medicines, primarily in Oncology, including Cardiovascular, Renal and Metabolism, Respiratory & Immunology, Vaccines & Infectious Diseases as well as Rare Diseases. AstraZeneca’s global headquarters is located in Cambridge, UK, with operations in more than 100 countries around the world, bringing innovative medicines to millions of patients globally. For more information, please visitwww.astrazeneca.com。

About AstraZeneca China

Since entering China in 1993, AstraZeneca has adhered to the principle of science first, focusing on innovation to meet the growing health needs of China and achieve its grand vision: "To innovate for the benefit of patients and become the most trusted healthcare partner in China." The company’s China headquarters is located in Shanghai, with regional headquarters established in Beijing, Guangzhou, Wuxi, Hangzhou, and Chengdu. AstraZeneca has production bases in Wuxi and Taizhou, Jiangsu Province, and a China logistics center in Wuxi. In China, AstraZeneca's business focus is primarily on treatment areas with the most urgent needs among Chinese patients, including oncology, cardiovascular, metabolic, renal, respiratory, gastrointestinal, vaccines and antibodies, autoimmune diseases, and rare diseases. In 2017, the China Health Internet of Things Innovation Center was established in Wuxi, aiming to explore innovative integrated solutions for full-process disease management through health IoT. In the same year, AstraZeneca formed Dizal (Jiangsu) Pharmaceutical Co., Ltd. as a joint venture with SDIC Innovation to accelerate local new drug development. In 2019, AstraZeneca announced a partnership with Wuxi to co-build the Wuxi International Life Science Innovation Park, leveraging global expertise for the benefit of Chinese patients. In 2020, AstraZeneca announced support for the "Internet Hospital" project. In 2021, AstraZeneca officially upgraded its Global R&D China Center in Shanghai and jointly launched the AstraZeneca CICC Healthcare Industry Fund with CICC Capital.

Statement

For reference only, not for any promotional purposes. If you have any questions, please consult a healthcare professional.

References:

^[1]. World Cancer Research Fund International. Ovarian Cancer Statistics. Available at https://www.wcrf.org/cancer-trends/ovarian-cancer-statistics/#:~:text=Latest%20ovarian%20cancer%20data,of%20ovarian%20cancer%20in%202020. Accessed September 2022.

^[2]. https://gco.iarc.fr/today/data/factsheets/populations/160-china-fact-sheets.pdf

^[3]. Hongmei Zeng, et al. Changing cancer survival in China during 2003–15: a pooled analysis of 17 population-based cancer registries[J]. Lancet Glob Health 2018; 6: e555–67.

^[4]. Ledermann JA, Raja FA, Fotopoulou C, Gonzalez-Martin A, Colombo N, Sessa C. Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up [J]. Ann Oncol 2013;24:Suppl 6:vi24-vi32

^[5]. Raja F, et al. Optimal first-line treatment in ovarian cancer. Ann of Oncol. 2012;23(10):118-127.

^[6]. NHS Choices, Ovarian Cancer Available at https://www.nhs.uk/conditions/ovarian-cancer/treatment/ Accessed September 2022.