BAVENCIO® Receives FDA Breakthrough Therapy Designation for First-Line Maintenance Treatment of Locally Advanced or Metastatic Urothelial Carcinoma.

  • Breakthrough Therapy Designation and Submission based on positive Phase III JAVELIN Bladder 100 study results
  • Supplemental Biologics License Application being reviewed under FDA Real-Time Oncology Review (RTOR) pilot program
  • JAVELIN Bladder 100 marks the first time any immunotherapy has demonstrated in Phase III an overall survival benefit vs standard of care in first-line locally advanced or metastatic urothelial carcinoma
San Francisco, California (UroToday.com) -- EMD Serono, the biopharmaceutical business of Merck KGaA, Darmstadt, Germany in the US and Canada, and Pfizer Inc. announced the completion of the submission of a supplemental Biologics License Application (sBLA) to the US Food and Drug Administration (FDA) for BAVENCIO® (avelumab)* for first-line maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma (UC). The FDA granted Breakthrough Therapy Designation to BAVENCIO for this indication, and the sBLA is being reviewed by the FDA under its Real-Time Oncology Review (RTOR) pilot program.


The application is based on positive results from an interim analysis of the Phase III JAVELIN Bladder 100 trial, which met its primary endpoint of overall survival (OS). In this study, BAVENCIO plus best supportive care (BSC) as first-line maintenance therapy significantly extended the survival of patients with previously untreated locally advanced or metastatic UC whose disease did not progress on induction chemotherapy, compared with BSC only. A statistically significant improvement was demonstrated in both co-primary populations: all randomized patients and patients with PD-L1–positive tumors. The safety profile for BAVENCIO in the trial was consistent with that in the JAVELIN monotherapy clinical development program. Detailed results from the JAVELIN Bladder 100 study will be presented at an upcoming medical congress.

"BAVENCIO is the first immunotherapy to demonstrate a statistically significant improvement in overall survival in a Phase III clinical trial in the first-line setting for patients with locally advanced or metastatic urothelial carcinoma," said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology, Pfizer Global Product Development. "Participation in the Real-Time Oncology Review program, coupled with the Breakthrough Therapy Designation, reflect the potential impact of BAVENCIO in this patient setting and provide the opportunity to work towards bringing this treatment option to patients as quickly as possible."
The RTOR program is intended to create a more efficient review process to bring safe and effective treatments to patients earlier, including drugs that are likely to demonstrate substantial improvements over currently available therapy. It allows the FDA to review clinical trial data from certain applications before the complete application is formally submitted. Review under the program does not guarantee or influence the approval of the application.1

Breakthrough Therapy Designation is a program created by the FDA to accelerate the development and review of medicines intended to treat serious or life-threatening diseases where the new treatment may be a substantial improvement over available therapy. In order to receive Breakthrough Therapy Designation, preliminary clinical evidence must indicate that the drug may demonstrate a significant improvement over available therapy on a clinically significant endpoint.2

"Given the poor prognosis for patients with advanced urothelial carcinoma, there is an urgent need for additional treatment options that improve overall survival," said Luciano Rossetti, Head of Global R&D for EMD Serono. "Our data highlight the potential for a first-line maintenance treatment approach with BAVENCIO to advance the current standard of care for previously untreated patients, and we are working with urgency toward our goal of bringing this regimen to patients."

"For the past 30 years, chemotherapy has been the first-line standard of care for patients with advanced urothelial carcinoma. While this is an effective short-term option for many patients, most will ultimately experience disease progression, underscoring a need for additional treatment options," said Petros Grivas, M.D., Ph.D., one of the principal investigators in the JAVELIN Bladder 100 trial. "Based on the positive overall survival results from JAVELIN Bladder 100, I believe avelumab has the potential to be practice-changing."

In 2017, the FDA approved BAVENCIO for the treatment of patients with locally advanced or metastatic UC who have disease progression during or following platinum-containing chemotherapy, or who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response and duration of response. JAVELIN Bladder 100 is the confirmatory study for the conversion to full approval.

*BAVENCIO is under clinical investigation for the first-line maintenance treatment of advanced UC. There is no guarantee that BAVENCIO will be approved for first-line maintenance treatment of advanced UC by any health authority worldwide.

About JAVELIN Bladder 100 
JAVELIN Bladder 100 (NCT02603432) is a Phase III, multicenter, multinational, randomized, open-label, parallel-arm study investigating first-line maintenance treatment with BAVENCIO plus BSC versus BSC alone in patients with locally advanced or metastatic UC. A total of 700 patients whose disease had not progressed after platinum-based induction chemotherapy as per RECIST v1.1 were randomized to receive either BAVENCIO plus BSC or BSC alone. The study achieved its primary endpoint of OS in each of the co-primary populations of all randomized patients and patients with PD-L1-positive tumors. Secondary endpoints include progression-free survival, anti-tumor activity, safety, pharmacokinetics, immunogenicity, predictive biomarkers and patient-reported outcomes in the co-primary populations. The safety profile for BAVENCIO in the trial was consistent with that in the JAVELIN monotherapy clinical development program.

Source: Serono, EMD. 2020. "EMD Serono And Pfizer Receive US FDA Breakthrough Therapy Designation And Submit Application For BAVENCIO® For First-Line Maintenance Treatment Of Locally Advanced Or Metastatic Urothelial Carcinoma". Prnewswire.Com.

  1. US Food and Drug Administration. Real-Time Oncology Review Pilot Program. 
  2. US Food and Drug Administration. Frequently Asked Questions: Breakthrough Therapies. 
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