Johnson & Johnson's Erdafitinib Approved in China for FGFR3-Altered Advanced Urothelial Carcinoma

Urothelial carcinoma is the most common type of bladder cancer. Bladder cancer is often associated with genetic mutations found in the patient's bladder or urothelial cells.Fibroblast Growth Factor Receptor (FGFR) is a class of receptor tyrosine kinases (RTK) that regulate important physiological processes such as cell growth and division. The family includes four receptors: FGFR1, FGFR2, FGFR3, and FGFR4.Studies have found that the high expression and mutations of FGFR lead to abnormal activation of its signaling pathway, allowing tumor cells to maintain growth in an "autonomous" manner, promoting cell proliferation, epithelial-mesenchymal transition, angiogenesis, as well as invasion, metastasis, and treatment resistance of tumor cells, which are closely related to the occurrence and development of various cancers.

ErdafitinibIt is an orally administered pan-FGFR tyrosine kinase inhibitor developed by Johnson & Johnson.With anti-tumor activity, it inhibits the activity of FGFR, blocks growth signals in tumor cells, and thereby achieves the purpose of treating malignant tumors.In April 2019, the FDA granted accelerated approval for the drug to treat adult patients with locally advanced or metastatic bladder cancer whose disease has progressed despite receiving platinum-based chemotherapy.According to the FDA's previous press release, this is the first targeted therapy approved for metastatic bladder cancer.The ProductInJanuary 2024FDA Approval ObtainedFull Approval, for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (mUC), these patients haveFGFR3Genetic variation and disease progression after at least one line of systemic treatment.

ErdafitinibApproval in the United States for the treatment of locally advanced or metastatic urothelial carcinoma was based on positive results from a Phase 3 clinical trial (THOR).The trial results showed that, when used as a second-line treatment, compared with chemotherapy, in patients who had previously received PD-1 or PD-L1 inhibitor treatment,ErdafitinibImproved patient survival and reduced the risk of death.At a median follow-up of 15.9 months,ErdafitinibThe median overall survival in the combination group and chemotherapy group was 12.1 months and 7.8 months, respectively;The median progression-free survival was 5.6 months and 2.7 months, respectively.。Compared with the chemotherapy group,ErdafitinibThe risk of death and disease progression in the group was reduced by 36% and 42%, respectively.

In terms of safety,ErdafitinibThe incidence of grade 3 or 4 treatment-related adverse events was similar between the combination group and the chemotherapy group (45.9% vs 46.4%).ErdafitinibThe incidence of treatment-related adverse events leading to death was lower (0.7% vs 5.4%). The study results have been published in the internationally renowned medical journal, The New England Journal of Medicine (NEJM）。

In China, according to the Chinese Drug Clinical Trial Registration and Information Disclosure Platform,Erdafitinib TreatmentAdvanced Urothelial CarcinomaPhase 3 Clinical Study(CTR20182097) was completed in October 2023. The study aimed to evaluate its comparison with chemotherapy or pembrolizumab.Progression after first-line treatment and carrying specificFGFRSubjects with advanced urothelial carcinomaEfficacy and Safety in China.The study recruited 629 subjects internationally and 44 subjects in China. Additionally,Erdafitinib targetsMultiple international multicenter phase 1 or phase 2 clinical studies on advanced non-small cell lung cancer, urothelial carcinoma, gastric cancer, esophageal cancer or cholangiocarcinoma, and advanced hepatocellular carcinoma have also been completed.

It is worth mentioning that Johnson & Johnson is also in developmentTargeted Release of Erdafitinib in the BladderA novel drug delivery system,Can be continuously released locally at a very low dose over a long period of time.Erdafitinib. The product has previously achieved success in Phase 1 trials.Positive ResultsThe complete response (CR) rate for high-risk non-muscle-invasive bladder cancer is 90%.

Looking forward toErdatiNi in ChinaThe approval and market launch can provide more cancer patients with new treatment options.

References:

[1] Johnson & Johnson announces the approval in China of Balversa® (erdafitinib tablets), the first targeted drug for treating patients with locally advanced or metastatic urothelial carcinoma with FGFR gene alterations. from https://mp.weixin.qq.com/s/yuy07QOdQuMqd3FhgfwTOw

[2]FDA approves first targeted therapy for metastatic bladder cancer. Retrieved April 12, 2019, from https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm635906.htm

[3] Bryant J Webber,et al.,(2024).Global cancer statistics 2022:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA:A Cancer Journal for Clinicians,DOI:10.3322/caac.21834.

[4] HOW BALVERSA® WORKS.Retrieved Jul 22,2024,from https://www.balversa.com/about-balversa/how-balversa-works/