Gemcitabine Intravesical System May Transform Bladder Cancer Treatment

For patients with Bacillus Calmette-Guérin (BCG)–unresponsive, high-grade, non-muscle-invasive bladder cancer (NMIBC), the treatment landscape has long been defined by a significant unmet need. Historically, the standard of care for these patients was radical cystectomy. However, recent years have brought new therapeutic options aimed at preserving the bladder and improving patients’ quality of life. Gary Steinberg, MD, a professor in the Department of Urology at Rush University, shed light on the latest addition to this expanding armamentarium: the FDA-approved gemcitabine intravesical system (Inlexzo).1

The gemcitabine intravesical system was previously known as TAR-200.

Steinberg outlined the current treatment algorithm, noting that prior to this new approval, clinicians had seen the introduction of several other agents with distinct mechanisms of action. These included the checkpoint inhibitor pembrolizumab (Keytruda), the oncolytic immunotherapy nadofaragene firadenovec-vncg (Adstiladrin), and a combination of intravesical BCG plus the IL-15 agonist nogapendekin alfa inbakicept-pmln (Anktiva).2-4 With the approval of the gemcitabine intravesical system, a fourth treatment has become available, offering a new, targeted approach to chemotherapy delivery.

Transcript:

There’s a tremendous unmet need for patients with BCG-unresponsive, high-grade disease. Traditionally, the standard of care has been radical cystectomy. Patients would like to avoid losing their bladder, especially if they don’t have any evidence of muscle-invasive disease. Over the past few years, we’ve seen new treatments that have been FDA-approved in this space. The first was pembrolizumab, which is a checkpoint inhibitor, which was approved by the FDA in [January] 2020. We’ve also seen [nadofraragene firadenovec], which is an oncolytic immunotherapy, which was FDA-approved in [December 2022]. Then, in the spring of 2024, we saw the combination of intravesical—that’s medication put inside the bladder—BCG plus [nogapendekin alfa inbakicept-pmln], which is an IL-15 agonist.

We’ve got 3 drugs, all with different mechanisms of action. One is a combination. Now, we have a fourth treatment that’s been FDA-approved [with] a different mechanism of action. The patients and the physicians that take care of them for their bladder cancer are truly benefiting tremendously. Having said that, it is an older chemotherapeutic drug that’s put into the [intravesical system] device. It is a better way to deliver intravesical chemotherapy. Many urologists today, because of the BCG-unresponsive disease, the BCG shortages, and their unfamiliarity with some of the new products, and shying away from using intravenous pembrolizumab, which is associated with its 11% to 12% grade 3 or greater immune-related adverse events. [They] have been using gemcitabine and docetaxel, an intravesical chemotherapy combination, [without] any FDA approval or with any prospective data. With the prospective data we have from the [gemcitabine intravesical system] in the phase 2 SunRISe-1 trial [NCT04640623], that will probably replace the gemcitabine/docetaxel because the numbers we see from the recent trial are, I believe, superior to what we see from intravascular gemcitabine/docetaxel.

References

1. U.S. FDA approval of INLEXZO™ (gemcitabine intravesical system) set to transform how certain bladder cancers are treated. News release. Johnson & Johnson. September 9, 2025. Accessed September 9, 2025. https://tinyurl.com/4zjz22z7
2. FDA approves pembrolizumab for BCG-unresponsive, high-risk non-muscle invasive bladder cancer. News release. FDA. January 8, 2020. Accessed September 12, 2025. https://tinyurl.com/29rsyr8m
3. FDA approves first adenoviral vector-based gene therapy for high-risk Bacillus Calmette-Guérin unresponsive non-muscle invasive bladder cancer. News release. FDA. December 16, 2022. Accessed September 12, 2025. https://tinyurl.com/4mx7vn23
4. FDA approves nogapendekin alfa inbakicept-pmln for BCG-unresponsive non-muscle invasive bladder cancer. News release. FDA. April 22, 2024. https://tinyurl.com/3m3kben9