Recently, Hengrui Pharmaceutical received the "Drug Registration Certificate" approved and issued by the State Drug Administration, approving the listing of a class 1 new drug developed by the company, PARP inhibitor fluzopalil capsule (®), for maintenance treatment of adult patients with advanced epithelial ovarian cancer, fallopian cancer or primary peritoneal cancer after complete or partial remission after first-line platinum chemotherapy. This is the third indication that fluzopalil has been approved for marketing, and fluzopril has become the second PARP inhibitor approved for this indication in the first-line population, which will provide a new option for first-line maintenance therapy for patients with advanced ovarian cancer.
This indication is approved for marketing based on a randomized, double-blind, controlled, multicenter phase Ⅲ clinical trial called FZPL-III-302 (FZOCUS-1). The results of this study show that [1] fluzapril monotherapy can significantly prolong PFS (progression-free survival) in patients with advanced ovarian cancer, and patients can benefit from maintenance therapy with or without gBRCA1/2 mutation, and the preliminary survival follow-up data show that the fluzoparil monotherapy group has the trend of OS (overall survival time).
New PARP inhibitor
Bring new benefits to the treatment of advanced ovarian cancer
The FZOCUS-1 study was conducted by 54 centers across the country. A total of 674 subjects were enrolled.RoyalstraightflushThe proportion at 2:1 was randomly assigned to the fluzopalil monotherapy group, the fluzoparil combined with apatinib group and the placebo group to receive maintenance treatment. the aim of this study was to evaluate the efficacy and safety of fluzopalil alone or fluzopalil combined with apatinib compared with placebo in the maintenance treatment of advanced ovarian cancer after first-line platinum chemotherapy. The main end point of the study is the Blind Independent Image Review Committee (BIRC) according to RECISTv1Royalstraightflush.1 PFS of standard evaluation.
During the oral presentation of the 55th annual meeting of the American Society of Gynecological Oncology (SGO) in 2024, the FZOCUS series of studies Leading PI and Professor Wu Lingying from the Cancer Hospital of the Chinese Academy of Medical Sciences announcedRoyalstraightflushThe latest clinical results of fluzopril monotherapy versus placebo in the FZOCUS-1 study were reviewed.
In the ITT (intended treatment) population, the BIRC evaluation showed that the mPFS of the fluzoparil monotherapy group had not yet been reached at the end of the data, while the mPFS of the placebo group was 11.1 months (HR=0.49). The fluzoparil monotherapy group significantly reduced the risk of disease progression or death by 51%.
Among people with gBRCA1/2 mutations, the mPFS of the fluzopril monotherapy group was not yet reached, the mPFS of the placebo group was 14.9 months (HR=0.40), and the fluzopril monotherapy group significantly reduced the risk of disease progression or death by 60%. In the gBRCA1/2 wild type population, the mPFS of the fluzoparil monotherapy group and the placebo group were 25.5 months and 8.4 months (HR=0.53), respectively, and the fluzoparil monotherapy group significantly reduced the risk of disease progression or death by 47%. That is, regardless of gBRCA status, compared with the control group, patients with advanced epithelial ovarian cancer treated with fluzopalil monotherapy after first-line platinum-containing chemotherapy reached CR/PR can significantly prolong PFS, reduce the risk of disease progression or death, and benefit the whole population.
In terms of safety, the overall tolerance is good. The termination rate of drug therapy is only 0.7%, which is currently a low termination rate of PARP inhibitors.
The treatment of advanced ovarian cancer is in urgent need.
Ovarian cancer is one of the most common gynecological malignant tumors, its incidence ranks third in gynecological tumors, and shows a rising trend year by year, the mortality rate is the highest in gynecological tumors, a serious threat to women's health. According to epidemiological studies, it is estimated that there will be about 61100 new cases of ovarian cancer in China in 2022, and about 32600 patients will die as a result.
The onset of epithelial ovarian cancer is hidden, and more than 70% of the patients are in the advanced stage of the disease at the time of treatment, and the treatment is mainly surgery and postoperative platinum-containing chemotherapy. Although most patients can achieve clinical remission after initial treatment, the 5-year survival rate of advanced patients is still less than 30%. Studies have shown that patients with advanced ovarian cancer do not receive any maintenance therapy after complete or partial remission, and the median progression-free survival (PFS) is only about 8.2-13.8 months [3,4]. First-line maintenance therapy is the key window for the initial treatment of ovarian cancer. The advent of PARP inhibitors has reshaped the diagnosis and treatment pattern of ovarian cancer, formed a new mode of "operation + chemotherapy + maintenance therapy", effectively delayed recurrence and prolonged disease-free survival.
Hengrui Medicine continues to meet the clinical needs of patients.
Fluzopril is a new type of oral polyadenosine diphosphate ribose polymerase (PARP) inhibitor developed by Hengrui Pharmaceuticals. It is the first PARP inhibitor developed independently in China, which can specifically kill BRCA mutated tumor cells. Two indications have been approved before: in December 2020, the company's fluzopalil capsule was approved for the treatment of platinum-sensitive recurrent ovarian cancer, fallopian cancer or primary peritoneal cancer with germline BRCA mutation (gBRCAm) after second-line or above chemotherapy.RoyalstraightflushIn June 2021, it was approved for maintenance treatment after complete or partial remission of platinum-containing chemotherapy in adult patients with platinum-sensitive recurrent epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer.
At present, Hengrui Medicine has registered a number of studies on fluzopalil, in addition to ovarian cancer, breast cancer, pancreatic cancer, prostate cancer and other tumors have also carried out related studies. In addition to first-line maintenance therapy for advanced epithelial ovarian cancer, fallopian cancer or primary peritoneal cancer, fluzopalide capsule has a variety of combined therapies, including apatinib, abirone, SHR-A1811, mFOLFIRINOX, etc. in the clinical development stage. The company's application for marketing license for the treatment of HER2-negative breast cancer patients with germline BRCA mutation (gBRCAm) by fluzopalil alone or in combination with apatinib mesylate was accepted by the State Drug Administration in April 2024 and included in the priority review list.
As an innovative international pharmaceutical enterprise, Hengrui Pharmaceutical has carried out the mission of "science and technology-based and creating a healthy life for mankind" for many years. It has been approved to list 14 self-developed Class 1 innovative drugs, 2 self-developed Class 2 new drugs and 2 cooperative imported innovative drugs in China. Over the years, Hengrui Medicine has been paying close attention to women's health, focusing on ovarian cancer, breast cancer, cervical cancer, gynecological infections and other areas of female multiple diseases, committed to providing patients with breakthrough and innovative drugs.
In the future, Hengrui Pharmaceutical will continue to be based on the needs of people's livelihood, race against the clock to promote the research and development of innovative drugs, and strive to develop more new and good drugs to serve healthy China and benefit patients around the world.
References:
[1] L. Wu,et al. Fuzuloparib as maintenance therapy in patients with advanced ovarian cancer after a response to first-line platinum-based chemotherapy: Results from a randomized, placebo-controlled, phase III trial.2024 SGO.
[2] Bingfeng Han, Rongshou Zheng, Hongmei Zeng, Shaoming Wang, Kexin Sun, Ru Chen, Li Li, Wenqiang Wei, Jie He, Cancer incidence and mortality in China, 2022, Journal of the National Cancer Center (2024).
[3] Moore K, Colombo N, Scambia G, et al. Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med 2018 + 379 (26): 2495-505. Doi: 10.1056/NEJMoa1810858 [published Online First: 20181021].
[4] Li N, Zhu J, Yin R, et al. Treatment With Niraparib Maintenance Therapy in Patients With Newly Diagnosed Advanced Ovarian Cancer: A Phase 3 Randomized Clinical Trial. JAMA Oncol 2023 doi: 10.1001/jamaoncol.2023.2283 [published Online First: 20230713].
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