Innovent Biologics, Inc., a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of cancer, metabolic, autoimmune and other major diseases announced that the National Medical Products Administration (NMPA) of China has accepted the New Drug Application (NDA) for FGFR1/2/3 inhibitor (pemigatinib) for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or rearrangement. Pemigatinib, a tyrosine kinase inhibitor discovered by Incyte, is licensed to Innovent for development and commercialization in Mainland China, Hong Kong, S.A.R., China, Macau, S.A.R., China and Taiwan, China. Pemigatinib, approved in the Taiwan, China market (trade name: Pemazyre?) on June 21, 2021, is Innovent's first approved small molecule drug and is also its fifth approved innovative drug.

The NDA submission to NMPA was based on the CIBI375A201 Study (NCT04256980), a bridging study of the FIGHT-202 (NCT02924376), which is a Phase 2, multi-center, open-label, single-arm study evaluating the safety and efficacy of pemigatinib – a selective fibroblast growth factor receptor (FGFR) inhibitor – in adult (age ≥18 years) patients with previously treated, locally advanced or metastatic cholangiocarcinoma with documented FGFR2 fusion or rearrangement. The primary endpoint in both studies was overall response rate (ORR) determined by an independent review committee (IRRC) Per RECIST V1.1. Among the 108 patients with FGFR 2 fusion/rearrangement enrolled in FIGHT-202 study, receiving pemigatinib at a dosage of 13.5mg, the ORR was 37% (95% CI：27.94%，46.86%), including 4 complete responses (3.7%) and 36 partial responses (33.3%). The median duration of response (DOR) was 8.08 months (95% CI: 5.65, 13.14) and the median progression-free survival (PFS) based on IRRC assessment was 7.03 months (95% CI: 6.08, 10.48). Pemigatinib could provide long lasting response with a median overall survival (OS) of 17.48 months (95% CI: 14.42, 22.93). The safety analysis, including 147 patients, demonstrated that pemigatinib was generally well tolerated. Hyperphosphatemia was the most common (58.5%) treatment-emergent adverse event (TEAE). TEAEs grade 3 or higher were reported in 68.7% of patients; the most frequent of which were hypophosphataemia (14.3%), arthralgia (6.1%), stomatitis (6.1%), hyponatraemia (5.4%), abdominal pain (5.4%) and fatigue (5.4%). CIBI375A201, according to the agreement with NMPA, has reached its predefined primary end point. Therefore, based on the promising results of CIBI375A201 as well as the impressive results of FIGHT-202, NDA has been submitted to the NMPA for review. For more information about FIGHT-202, please visit https://clinicaltrials.gov/ct2/show/NCT02924376  or https://ascopubs.org/doi/abs/10.1200/JCO.2021.39.15_suppl.4086

Dr. Hui Zhou, Senior Vice President of Clinical Development of Innovent, stated: 'Cholangiocarcinoma is the second most common primary liver cancer with a high incidence in Asia due to relatively widespread infection of HBV and parasites.' He emphasized that a significant portion of patients receive an initial diagnosis of unresectable and/or metastatic status with limited therapy choice. Data from previous clinical trials of pemigatinib in participants with advanced cholangiocarcinoma with FGFR2 fusion as second line or later treatment has not only shown satisfactory safety results but also revealed compelling efficacy signals. With the refractory subjects being seen as the more challenging population and based on the promising data, we believe that patients with FGFR2 fusion or rearrangement may benefit from targeted therapies. The NDA submission is a great clinical milestone, and we are looking forward to the approval of pemigatinib in the treatment of eligible patients with cholangiocarcinoma in China', Dr. Zhou highlighted.

About Advanced Cholangiocarcinoma and FGFR2 Rearrangement

Cholangiocarcinoma is a malignant tumour originated from biliary epithelium cells and it is categorized as intrahepatic or extrahepatic based on anatomical location of origin. The incidence of cholangiocarcinoma has been increasing progressively over the past decade. Surgery is the first priority for patients with resectable disease. However, most cholangiocarcinomas has been in advanced and/or metastatic status at diagnosis and lost the chance for surgical resection. The treatment options for patient who relapse after surgery or have advanced / metastatic disease are limited and the recommended therapy method is systemic chemotherapy with gemicitabine plus cisplatin, which has a medium overall survival of less than a year.

Aberrant signaling through FGFR resulting from gene amplification or mutation, chromosomal translocation, and ligand-dependent activation of the receptors has been demonstrated in multiple types of human cancers. Fibroblast growth factor receptor signaling contributes to the development of malignancies by promoting tumor cell proliferation, survival, migration, and angiogenesis. Results from early clinical studies of selective FGFR inhibitors, including pemigatinib, have shown a tolerable safety profile for the class and preliminary signs of clinical benefit in participants with FGF/FGFR alterations.

About Pemigatinib

In April 2020, the U.S. Food and Drug Administration (FDA) approved Incyte's Pemazyre? (pemigatinib), a selective, oral inhibitor of FGFR isoforms 1, 2 and 3, for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or rearrangement as detected by an FDA-approved test. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

In Japan, Pemazyre is approved for the treatment of patients with unresectable biliary tract cancer with a FGFR2 fusion gene, worsening after cancer chemotherapy. In Europe, Pemazyre is approved for the treatment of adults with locally advanced or metastatic cholangiocarcinoma with a FGFR2 fusion or rearrangement that have progressed after at least one prior line of systemic therapy. Pemazyre is marketed by Incyte in the United States, Europe and Japan. 

In June 2021, Taiwan, China Food and Drug Administration (TFDA) approved Pemazyre? (pemigatinib) for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a FGFR2 fusion or rearrangement.

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 three assets in Mainland China, Hong Kong, S.A.R., China, Macau, S.A.R., China and Taiwan, China. In March 2020, Innovent announced that the first patient was dosed in the pivotal registrational trial evaluating pemigatinib in patients with advanced cholangiocarcinoma in China.

Pemazyre is a trademark of Incyte Corporation.

About Innovent

Inspired by the spirit of "Start with Integrity, Succeed through Action," Innovent's mission is to develop, manufacture and commercialize high-quality biopharmaceutical products that are affordable to ordinary people. Established in 2011, Innovent is committed to developing, manufacturing and commercializing high-quality innovative medicines for the treatment of cancer, autoimmune, metabolic and other major diseases. On October 31, 2018, Innovent was listed on the Main Board of the Stock Exchange of Hong Kong, S.A.R., China Limited with the stock code: 01801.HK.

Since its inception, Innovent has developed a fully integrated multi-functional platform which includes R&D, CMC (Chemistry, Manufacturing, and Controls), clinical development and commercialization capabilities. Leveraging the platform, the company has built a robust pipeline of 24 valuable assets in the fields of cancer, metabolic, autoimmune disease and other major therapeutic areas, with 5 products – TYVYT? (sintilimab injection), BYVASDA? (bevacizumab biosimilar injection), SULINNO? (adalimumab biosimilar injection), HALPRYZA? (rituximab biosimilar injection) and PEMAZYRE? (pemigatinib oral inhibitor) – officially approved for marketing, sintilimab's Biologics License Application (BLA) acceptance in the U.S., 5 assets in Phase 3 or pivotal clinical trials, and an additional 14 molecules in clinical trials. In 2019, TYVYT? was the first PD-1 inhibitor included in the National Reimbursement Drug List (NRDL) and the only PD-1 inhibitor included in the NRDL in that year.

Innovent has built an international team with advanced talent in high-end biological drug development and commercialization, including many global experts. The company has also entered into strategic collaborations with Eli Lilly and Company, Adimab, Incyte, MD Anderson Cancer Center, Hanmi and other international partners. Innovent strives to work with many collaborators to help advance China's biopharmaceutical industry, improve drug availability and enhance the quality of the patients' lives.