HORSHAM, Pa.—The Janssen Pharmaceutical Companies of Johnson & Johnson announced today that Balversa (erdafitinib) has received accelerated approval from the U.S. Food and Drug Administration (FDA) for the treatment of adults with locally advanced or metastatic urothelial carcinoma (mUC) which has susceptible fibroblast growth factor receptor (FGFR)3 or FGFR2 genetic alterations, and who have progressed during or following at least one line of prior platinum-containing chemotherapy, including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy.
Balversa is the first FGFR kinase inhibitor approved by the FDA. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Today’s approval follows FDA Breakthrough Therapy Designation in March 2018, and Priority Review Designation of the New Drug Application submitted in September 2018.
“I’ve spent my career specializing in the care of patients with metastatic urothelial carcinoma and understand the need for new treatments for this disease,” said Arlene O. Siefker-Radtke, M.D., professor of Genitourinary Medical Oncology at The University of Texas MD Anderson Cancer Center, and lead study investigator. “Balversa is an important new therapy for this small subset of patients with urothelial carcinoma who, up until now, had limited treatment options.”
Urothelial carcinoma, also known as transitional cell carcinoma, starts in the innermost lining of the bladder. It is the most common and frequent form of bladder cancer, representing more than 90 percent of all bladder cancers. About one in five patients with mUC have a FGFR genetic alteration. FGFRs can be activated by genetic alterations in a variety of tumor types, and these alterations may lead to increased tumor cell growth and survival.
Balversa, a once-daily oral FGFR kinase inhibitor, received accelerated approval based on results from a Phase 2 clinical trial, a multicenter open-label, single-arm study of 87 patients with disease that had progressed on or after at least one prior chemotherapy and that had at least one of the following genetic alterations: FGFR3 gene mutations (R248C, S249C, G370C, Y373C); or FGFR gene fusions (FGFR3-TACC3, FGFR3-BAIAP2L1, FGFR2-BICC1, FGFR2-CASP7); as determined by a clinical trial assay performed at a central laboratory. The results demonstrated a 32.2 % objective response rate (ORR) as assessed by Blinded Independent Review Committee [95% CI(22.4, 42.0)]. Responders included patients who had previously not responded to anti PD-L1/PD-1 therapy.
In the trial, ORR was defined as the percentage of patients with measurable lesions achieving a complete response [2.3 %] or partial response [29.9 %] to treatment using the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) criteria, a standard way to measure how well a patient responds to treatment based on whether tumors shrink, stay the same or get bigger as assessed per investigator. Results also showed a median duration of response of 5.4 months [95% CI(4.2, 6.9)] in patients treated with Balversa. There were no confirmed responses to Balversa in the FGFR2 fusion patient population (n=6). Data from the BLC2001 study were presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, and were recognized as a “Best of ASCO” selection.
Peter Lebowitz, M.D., Ph.D., global therapeutic area head, Oncology, Janssen Research & Development added, “We recognize the significant unmet need that persists in the treatment of men and women diagnosed with this form of urothelial carcinoma, and we have worked expeditiously to develop Balversa for patients in close consultation with the FDA. We look forward to the continued development of Balversa to understand how this important new therapy may further inform the care of patients with metastatic urothelial carcinoma and its investigational use in other cancers where FGFR alterations may be present in the future.”
The FDA has simultaneously approved a companion diagnostic for use with Balversa, the QIAGEN therascreen FGFR RGQ Reverse-transcription (RT)-polymerase chain reaction (PCR) kit, which is the first PCR-based companion diagnostic approved to detect FGFR alterations. The therascreen FGFR test detects the presence of FGFR alterations in the tumor tissue of patients with mUC. If one or more of the genetic alterations or fusions are detected, the patient may be a candidate for treatment with Balversa.
“The FDA approval of Balversa represents our commitment to deliver much-needed therapies for devastating diseases, including metastatic urothelial carcinoma where there is a lack of therapeutic options. We are also pleased to see the simultaneous FDA approval of a companion diagnostic with Balversa, which will offer a more personalized approach to therapy for healthcare professionals to treat their patients,” concluded Mathai Mammen, M.D., Ph.D., global head, Janssen Research & Development.