▎WuXi AppTec Content Team Report

On October 11, the official website of the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China announced that AstraZeneca andAbbVieCommonThe marketing application for the declared Olaparib Tablets has been accepted. According to publicly available information,Olaparib (olaparib）It is a PARP inhibitor, developed byAstraZeneca and MSD (MSD) jointly develop and commercialize。

Screenshot source:CDE Official Website

Olaparib is a“first-in-class”PARP inhibitor, aBlocking homologous recombination repair (HRR) defects (e.g.,BRCA1And/OrBRCA2Targeted therapeutic agents for DNA damage repair pathways (DDR) in cells/tumors with defects caused by mutations or other novel endocrine drugs.The use of Olaparib to inhibit PARP can lead to the binding of PARP with DNA single-strand breaks, thereby preventing the formation and collapse of replication forks, and resulting in DNA double-strand breaks and cancer cell death.。Olaparib may also help enhance immunogenicity and increase the impact of anti-tumor immune responses.

Public information shows that Olaparib, jointly developed and commercialized by AstraZeneca and Merck, can be used both as a single therapy and in combination with other potential drugs. The two companies are independently developing Olaparib and combining it with their respective PD-L1 and PD-1 drugs, Durvalumab and Pembrolizumab. AstraZeneca and Merck are also collaboratively exploring its effects as both a monotherapy and combination therapy on various cancer types with PARP-dependent tumors.

According to a recent press release from AstraZeneca, olaparib has now been approved in multiple countries for various types of cancer, including:

• Platinum-sensitive recurrent ovarian cancerMaintenance treatment, as well as single-agent therapy and in combination with bevacizumab forBRCAMutation (BRCAm) Homologous recombination repair deficiency (HRD) positive advancedOvarian CancerFirst-line maintenance treatment;

• For germlineBRCAMutation (gBRCAm), HER2-negative metastaticBreast Cancer(In the EU and Japan, including locally advanced breast cancer);Used forgBRCAm, HER2-negativeHigh-Risk Early-Stage Breast Cancer(In Japan, including allBRCAm HER2-negative high-risk early breast cancer);

• For gBRCAmMetastaticPancreatic Cancer；

• In combination with abiraterone for metastatic disease without clinical indication for chemotherapyCastration-Resistant Prostate Cancer(mCRPC) Treatment (EU Only) andBRCAm mCRPC (United States and Japan);As a monotherapy for HRR gene mutation mCRPC, used in patients with progression following prior NHA treatment (BRCAm is only valid in the EU and Japan).

In China, Olaparib was first approved for marketing in 2018.Maintenance Treatment for Platinum-Sensitive Recurrent Ovarian Cancer Patients. Since then, the product has been approved for multiple indications in China, includingBRCAAdvanced MutationOvarian CancerFirst-line maintenance treatment, carrying germline or somaticBRCAMutated and previously treated failedMetastatic Castration-ResistantProstate CancerTreatment of adult patients, in combination with bevacizumab for HRD-positive advancedOvarian CancerFirst-line maintenance therapy. In January 2024, olaparib monotherapy or in combination with endocrine therapy forGermlineBRCA1/2Adjuvant Treatment for Adult Patients with HER2-Negative Early High-Risk Breast Cancer with MutationsNew Indication Marketing Application AlsoAccepted。

According to the official website of the China Drug Clinical Trial and Information Disclosure Platform, researchers are conducting more than ten Phase III clinical trials related to olaparib, including the following ongoing Phase III clinical trials:

• A study inAchieved remission after receiving standard first-line platinum-based chemotherapyBRCAWild-type advanced-stage (FIGO III-IV) high-grade serous or endometrioid ovarian cancerInternational multicenter Phase 3 study of olaparib monotherapy in subjects (MONO-OLA1);

• An international multicenter Phase 3 clinical study（DUO-O）`, aiming to`ConfirmNewly Diagnosed Advanced Tumor-FreeBRCAAdult patients with mutated epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancerThe efficacy of moderate-dose伐利尤单抗 and 奥拉帕利;

• InPlatinum-sensitive recurrent ovarian cancer with CR or PR after platinum-based chemotherapyAn international multicenter Phase 3 study evaluating the efficacy of olaparib monotherapy maintenance treatment in patients;

• Evaluation of Olaparib forgBRCA1/2Mutated and High-Risk HER2-Negative Primary Breast CancerInternational multicenter Phase 3 study on the efficacy and safety of patients;

• Evaluation of Olaparib After First-Line Platinum ChemotherapyBRCAA Placebo-Controlled International Multicenter Phase 3 Study of Single-Agent Maintenance Therapy in Patients with Mutated Advanced Ovarian Cancer.

This timeOlaparibFiling for a new indication in China means that the product's development in China has reached a new milestone.

[2] Lynparza and Imfinzi Combination Therapy Approved in the EU for Treatment of Advanced or Recurrent Endometrial Cancer Patients with Proficient Mismatch Repair. Retrieved Aug 15，20234, From https://www.astrazeneca.com.cn/zh/media/press-releases/2024/08-15-01.html