Date: 06-Mar-2020

Innovent Biologics begins patient enrollment in pivotal trial of Pemigatinib to treat advanced cholangiocarcinoma in China

Innovent Biologics Inc, a world-class biopharmaceutical company that develops and commercialises high quality medicines for the treatment of cancer, autoimmune, metabolic and other major diseases, announced that the company achieved first patient dosing in a pivotal phase 2 registrational trial of pemigatinib (IBI375), a FGFR1/2/3 inhibitor, in China. The objective of this study is to evaluate the efficacy and safety of pemigatinib in patients with advanced cholangiocarcinoma with FGFR2 fusions or rearrangements who have progressed from at least one prior systemic therapy in China. Dr. Jian Zhou, vice president of Zhongshan Hospital, Fudan University stated, "The intrahepatic cholangiocarcinomas (iCCAs) account for approximately 15~20% of all liver tumors with a significant uptrend. Most patients with iCCAs are not amenable to surgical resection with curative intent due to local invasion and metastasis at initial visit. Currently, the chemotherapy of gemcitabine combined with cisplatin is recommended as a first-line treatment for patients with advanced cholangiocarcinoma, with 15~26% overall response rate (ORR). Unfortunately, most patients will develop resistance to this chemotherapy, and the effective alternative therapies are limited. A previous study of pemigatinib, a FGFR targeted therapy, in patients with CCA who have FGFR2 fusions or rearrangements demonstrated significant efficacy and safety, with 36% ORR, 7.5 months median duration of response (DOR), and 21.1 months preliminary overall survival (OS), providing new hope for patients. We anticipate to achieve promising results for the trial of pemigatinib in Chinese patients with advanced cholangiocarcinoma." Dr. Hui Zhou, vice president and head of Oncology Strategy and Medical Sciences of Innovent, stated, "Cholangiocarcinoma, a malignant tumor arising from biliary epithelium cells, has poor prognosis and high unmet treatment needs due to lack of effective treatment. We are glad that the first patient dosing in the Phase 2 clinical trial of pemigatinib has been completed, and the data of the study will be used to support the new drug application (NDA) for pemigatinib in China. It is an important milestone for pemigatinib to enter the Chinese market and we believe this trial in China will benefit patients with cholangiocarcinoma who have FGFR fusions or rearrangements and provide more treatment options to clinicians." Cholangiocarcinoma is a malignant tumour arising from biliary epithelium cells, and cholangiocarcinomas are categorized as intrahepatic or extrahepatic according to anatomical location. The incidence of cholangiocarcinoma has increased progressively over the past years. Surgical resection remains the mainstay of potentially curative treatment, but only a minority of patients have early stage disease that is amenable to surgical resection with curative intent. Unfortunately, most patients who have undergone a surgical resection will relapse. For patients with advanced or unresectable cholangiocarcinoma, the available systemic therapies are of limited effectiveness: the median overall survival with the current standard-of-care chemotherapy regimen is less than 1 year. Fibroblast growth factor receptors (FGFRs) play an important role in tumor cell proliferation and survival, migration and angiogenesis (the formation of new blood vessels). Activating fusions, rearrangements, translocations and gene amplifications in FGFRs are closely correlated with the development of various cancers. Amounts of studies have demonstrated that FGFR2 fusion/rearrangement can lead to the development and/or progression of cholangiocarcinoma, FGFR- targeted therapeutics have produced striking benefits in these patients. Pemigatinib is a potent, selective, oral inhibitor of FGFR isoforms 1, 2 and 3 which, in preclinical studies, has demonstrated selective pharmacologic activity against cancer cells with FGFR alterations. In November of 2019, the United States Food and Drug Administration (US FDA), accepted for Priority Review the NDA for pemigatinib, submitted by Incyte Biosciences International Sàrl (Incyte), for the treatment of previously treated, locally advanced cholangiocarcinoma with FGFR2 fusions or rearrangements. The Prescription Drug User Fee Act (PDUFA) target action date is May 30, 2020. Previously, the US FDA granted pemigatinib Breakthrough Therapy designation for the treatment of previously treated, advanced/metastatic or unresectable FGFR2 translocated cholangiocarcinoma. Additionally, the US FDA granted pemigatinib Orphan Drug designation for the treatment of cholangiocarcinoma, a designation granted to investigational compounds intended for the safe and effective treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 200,000 people. In December 2018, Innovent and Incyte entered into a strategic collaboration for three clinical-stage product candidates discovered and developed by Incyte, including pemigatinib (FGFR1/2/3 inhibitor). Under the terms of the agreement, Innovent has received the rights to develop and commercialize the pemigatinib and two other assets in Mainland China, Hong Kong, Macau and Taiwan.