Johnson & Johnson (J&J) has announced the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for TAR-200, an investigational intravesical drug-releasing system, for the treatment of patients with Bacillus Calmette-Guérin (BCG)-unresponsive high-risk non-muscle-invasive bladder cancer (HR-NMIBC) with carcinoma in situ (CIS), with or without papillary tumors. The FDA has accepted the application for Real-Time Oncology Review (RTOR). This regulatory pathway aims to accelerate the availability of promising therapies for cancer patients. The application is supported by data from the Phase 2b SunRISe-1 study, which demonstrated a high complete response rate and durable responses with TAR-200 monotherapy.
Clinical Efficacy of TAR-200
The submission is based on data from the Phase 2b SunRISe-1 trial (NCT04640623), a randomized, parallel-assignment, open-label study evaluating the safety and efficacy of TAR-200 monotherapy in patients with BCG-unresponsive HR-NMIBC who are ineligible for or have elected not to undergo radical cystectomy. The primary endpoint was complete response (CR) rate at any time point. Secondary endpoints included duration of response (DOR), overall survival (OS), pharmacokinetics, quality of life, safety, and tolerability.
Data presented at the European Society for Medical Oncology (ESMO) 2024 Congress showed an 83.5% complete response (CR) rate in patients treated with TAR-200. At a median follow-up of nine months, 82% of responders maintained their response. The safety profile was also favorable, with a low occurrence of Grade 3 or higher treatment-related adverse events (TRAEs) (9%); 6% of patients discontinued treatment due to TRAEs, and no treatment-related deaths were reported.
TAR-200: A Novel Intravesical Drug Delivery System
TAR-200 is an investigational intravesical drug-releasing system designed to provide sustained local delivery of gemcitabine directly into the bladder. The system is placed into the bladder by a healthcare professional using a co-packaged urinary placement catheter in an outpatient setting, typically in under five minutes and without the need for anesthesia. This sustained release aims to maximize drug exposure to the tumor while minimizing systemic exposure, potentially reducing systemic side effects.
Addressing Unmet Needs in HR-NMIBC
HR-NMIBC represents a significant challenge in bladder cancer management. It is characterized by a high risk of recurrence and progression to muscle-invasive bladder cancer, which often necessitates radical cystectomy (complete bladder removal). Radical cystectomy can have significant morbidity and impact on quality of life, particularly in older patients who may be unfit for surgery. Current treatment options for BCG-unresponsive HR-NMIBC are limited, highlighting the need for new, effective, and less invasive therapies.
"Upon approval, TAR-200 promises to be a meaningful additional treatment option for certain patients with NMIBC, addressing a critical need for people who have had relatively limited therapeutic alternatives. Many patients face life-altering surgical options such as radical cystectomy, which is complete bladder removal," said Yusri Elsayed, M.D., M.H.Sc., Ph.D., Global Therapeutic Head, Oncology, Johnson & Johnson Innovative Medicine.
Regulatory Designations and Ongoing Studies
In December 2023, the FDA granted Breakthrough Therapy Designation (BTD) to TAR-200 for the treatment of adult patients with BCG-unresponsive HR-NMIBC with CIS who are ineligible for or have elected not to undergo radical cystectomy. This designation underscores the potential of TAR-200 to address a significant unmet medical need.
J&J is also evaluating TAR-200 in other clinical trials, including SunRISe-3, which is testing the drug with and without cetrelimab in BCG-naive NMIBC patients, and SunRISe-5, a phase 3 trial of TAR-200 as a second-line therapy for high-risk NMIBC patients who have previously received BCG treatment and are unwilling or unable to have a cystectomy.
