Janssen Submits Erdafitinib Import Application in China, Paving Way for Market Entry

Original: Xiao Yaowan

Recently, the CDE website showed that Erdafitinib tablets, developed by Janssen Pharmaceuticals under Johnson & Johnson, have submitted an import clinical application in China and have been accepted. This blockbuster bladder cancer treatment drug has thus embarked on its path to market launch in China, holding promise to bring innovative targeted therapy solutions to domestic bladder cancer patients.

Source: CDE

Unmet Clinical Needs

In the WHO Classification of Tumours: Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs, the histological types of bladder cancer include urothelial carcinoma of the bladder, squamous cell carcinoma of the bladder, and adenocarcinoma of the bladder.

According to information released by the FDA, bladder cancer is the sixth most common cancer in the United States, with approximately 15,000 new cases diagnosed each year. For patients with metastatic disease, particularly those with recurrent or refractory conditions, the prognosis is poor due to rapid tumor progression and a lack of effective treatment options. For instance, the relative five-year survival rate for patients with stage IV metastatic bladder cancer is only 5%. There is an urgent need for new therapies to alleviate disease burden and prolong survival in these patients, representing a significant unmet medical need in this field.

First FDA-Approved Targeted Therapy for Metastatic Bladder Cancer

In vivo, fibroblast growth factor receptors (FGFRs) participate in regulating critical physiological processes, including cell growth and division. Genetic mutations occurring in various tumors can lead to the aberrant activation of these receptors, ultimately promoting the genesis and proliferation of tumor cells. Consequently, the development of novel anticancer drugs targeting FGFR inhibitors has emerged as a prominent area of research in cancer targeted therapy in recent years. Statistics indicate that approximately one-fifth of patients with recurrent and refractory bladder cancer harbor alterations in the fibroblast growth factor receptor (FGFR).

Erdafitinib was initially developed by Astex Pharmaceuticals. In 2008, Janssen Pharmaceuticals entered into a global collaboration agreement with Astex for erdafitinib, through which Janssen obtained the rights to develop and commercialize the drug. In March 2018, the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation to erdafitinib for the treatment of urothelial carcinoma, and the New Drug Application (NDA) received Priority Review status.

In April 2019, erdafitinib tablets received accelerated approval from the U.S. Food and Drug Administration (FDA) under the brand name Balversa, for the treatment of locally advanced or metastatic bladder cancer that has progressed despite prior platinum-based chemotherapy, becoming the first targeted therapy worldwide for metastatic urothelial carcinoma. Balversa is an oral tablet available in strengths of 3 mg, 4 mg, or 5 mg of erdafitinib per tablet.

Pivotal Clinical Trial

It is reported that the FDA’s accelerated approval of erdafitinib was based on efficacy data from a Phase II clinical trial. The study enrolled a total of 87 patients with locally advanced or metastatic urothelial carcinoma who had experienced disease progression after receiving at least one prior platinum-containing chemotherapy regimen and harbored FGFR3 genetic mutations or FGFR gene fusions.

Publicly available clinical trial results showed that patients treated with Erdafitinib achieved an objective response rate of 32.2%, with a complete response (CR) rate of 2.3% and a partial response (PR) rate of 29.9%. The median time to tumor progression or death was 5.4 months.

Multi-Indication Clinical Study

Given the extensive physiological processes regulated by FGFR in vivo, and the promoting role of gene mutations in tumorigenesis and progression across various tumor types, the development of FGFR inhibitors can target different types of tumors from a therapeutic perspective, with potentially diverse treatment indications.

According to the publicly available information on ClinicalTrials.gov, there are a total of 17 clinical trials listed for Erdafitinib, including 11 Phase II trials and 1 Phase III trial. The indications covered in these trials include advanced malignant solid tumors, non-Hodgkin lymphoma, prostate cancer, non-small cell lung cancer, urothelial carcinoma, hepatocellular carcinoma, breast cancer, and relapsed/refractory multiple myeloma, among others.

In March 2018, the Phase III clinical trial of Erdafitinib was initiated, aiming to enroll 631 participants. The study is designed to compare the clinical efficacy of Erdafitinib with chemotherapy agents such as vincristine and docetaxel, as well as pembrolizumab, in the treatment of urothelial carcinoma, and is expected to conclude by the end of 2021.