Express | the FGFR inhibitor introduced by Innovent Bio was approved in Chinese mainland for the treatment of cholangiocarcinoma

▎ WuXi AppTec content team reports

On April 6, the official website of China's State Food and Drug Administration (NMPA) announced that the FGFR1/2/3 inhibitor pemigatinib tablets introduced by Cinda Bio from Incyte have been approved for marketing. Public information shows that the indications for the drug to be approved this time are specific advanced, metastatic or non-surgically resectable adult patients with cholangiocarcinoma. Previously, the drug has been approved for the treatment of cholangiocarcinoma in Taiwan and Hong Kong, China.

Screenshot source: NMPA official website

Genetic variations of fibroblast growth factor receptors (FGFR) are present in many types of human tumors, mainly through FGFR gene amplification, mutations, chromosomal translocations, and ligand-dependent activation caused by abnormal FGFR signaling. FGFR signaling promotes the development of malignant tumors by promoting tumor cell proliferation, survival, migration, and angiogenesis.

Pemigatinib is a potent selective oral small molecule inhibitor developed by Incyte for FGFR subtypes 1/2/3 that prevents cancer cells from growing and spreading by blocking FGFR-mediated signaling pathways in tumor cells. In December 2018, Innovent Bio entered into a partnership with Incyte to obtain development and commercialisation rights for pemigatinib in Chinese mainland, Hong Kong, Macau and Taiwan.

At present, pemigatinib has been approved for the treatment of patients with cholangiocarcinoma in the United States, Europe and Japan. In China, pemigatinib was approved for the treatment of cholangiocarcinoma patients in June 2021 and January 2022 in Taiwan and Hong Kong, respectively. Chinese mainland, the Drug Evaluation Center (CDE) of the State Drug Administration of China accepted the listing application of pemigatinib in July 2021 and included it in the priority review for the treatment of adult patients with advanced, metastatic or non-inoperable cholangiocarcinoma who have received at least one previous systemic treatment and have been tested to have FGFR2 fusion or rearrangement.

Image source: CDE official website

At the annual meeting of the European Society of Oncology (ESMO) held in September 2021, Innovent Bio published the results of pemigatinib's Phase 2 study in people with advanced cholangiocarcinoma in China. It was an open-arm, single-arm, multicenter Phase 2 study to evaluate the efficacy and safety of pemigatinib in patients with advanced cholangiocarcinoma in China who had previously received at least one systemic treatment failure, FGFR2 fusion, or rearrangement positivity. The study is also a bridging test within China of PEMIGATINIB Overseas Research WEIGHT-202. The primary endpoint of the clinical trial was that 31 subjects included in part II of the study achieved the objective response rate (ORR) assessed by the Independent Imaging Evaluation Board (IRRC) according to the RECIST v1.1 criteria.

The study data showed that of the 30 rated efficacy populations in the second part of the study, 15 patients achieved IRRC-confirmed disease remission, and the primary endpoint indicator ORR reached 50%. At the median follow-up of 5.13 months, 12 patients were still in remission and the median duration of remission (DOR) had not yet been reached. By the data deadline, progression-free survival (PFS) data were not mature, with only 6 PFS events occurring and a disease control rate (DCR) of 100%. In addition, pemigatinib has also shown good safety.

Cholangiocarcinoma is a malignant tumor originating from bile duct epithelial cells, which can be divided into two categories: intrahepatic bile duct carcinoma and extrahepatic bile duct carcinoma according to the site of occurrence. Public information shows that surgery is the only treatment with the potential to cure cholangiocarcinoma, but most patients with cholangiocarcinoma are unresectable tumors or metastases at the time of initial diagnosis, and the opportunity for radical surgical cure is lost. New treatment options are urgently needed in patients with non-resectable, metastatic, or postoperatively recurrent cholangiocarcinoma.

It is hoped that pemigatinib can come to the patient as soon as possible and let the patients with cholangiocarcinoma have new diagnosis and treatment options.

Resources:

[1] April 6, 2022, the drug approval certificate is to be released. Retrieved Apr 6，2022, from https://www.nmpa.gov.cn/zwfw/sdxx/sdxxyp/yppjfb/20220406084341107.html

2] Innovent Biologics announced pemigatinib's Phase 2 study in people with advanced cholangiocarcinoma in China at the 2021 ESMO Online Annual Meeting. Retrieved Sep 17，2021, from http://cn.innoventbio.com/#/news/293

[3] Innovent Announces that the NmPA has accepted applications for the listing of FGFR1/2/3 inhibitors (pemigatinib tablets) for the treatment of adult patients with advanced, metastatic or non-inoperable cholangiocarcinoma who have received at least one previous systemic treatment and have been tested to have FGFR2 fusion or rearrangement. Retrieved July 9，2021, from http://cn.innoventbio.com/#/news/278

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