Intravesical Mitomycin Receives FDA Approval for Recurrent Non-Muscle-Invasive Bladder Cancer

On June 12, 2025, the US Food and Drug Administration (FDA) approved mitomycin intravesical solution (Zusduri, UroGen Pharma) for adults diagnosed with recurrent, low-grade, intermediate-risk, non-muscle-invasive bladder cancer (LG-IR-NMIBC).

What Is Mitomycin Intravesical Solution?

Mitomycin (particularly the mitomycin-C form) is a potent cytotoxic (cell-killing) chemotherapy agent used in cancer treatment. It is an antibiotic with alkylating-agent-like activity. Streptomyces caespitosus is the bacterium from which it is naturally derived. It stops cell division by forming DNA cross-links (an effect similar to DNA alkylation). It acts during the G1 and S phases of the cell cycle. Although mitomycin is structurally derived from an antibiotic, it is used for its antineoplastic (tumor-suppressing) effect rather than its antibacterial activity.

Mitomycin intravesical solution (brand name Zusduri), unlike conventional mitomycin-C, is supplied in a special gel formulation and is designed for intravesical (within the bladder) administration using a drug-delivery technology platform. This formulation was developed to remain on the bladder wall longer than conventional liquid mitomycin.

🔬 What Makes This Drug Different?

Conventional mitomycin is usually administered as a liquid and is rapidly eliminated in the urine. Because Zusduri uses a special technology, it gels at body temperature and adheres to the bladder wall.

This allows the drug to:

• Remain in the bladder for longer periods
• Become more effective in its action
• Cause fewer side effects

⚙️ What Technology Is Used?

The technology used to manufacture this drug is called a “temperature-sensitive gel” (thermal gel technology) . The drug is liquid at room temperature. However, it gels when it reaches body temperature and adheres to the bladder wall, enhancing its effect.

FDA Approval in Early-Stage Bladder Cancer Based on the ENVISION Study

The approval was based on the ENVISION (NCT05243550) study, a multicenter, single-arm clinical trial involving 240 patients. All patients had previously undergone TURBT (transurethral resection of bladder tumor) and met 1 or 2 of the following criteria:

• Multiple tumors
• A single tumor larger than 3 cm
• Recurrence within 1 year

Patients received 75 mg of mitomycin solution into the bladder via a catheter once weekly for 6 weeks. Assessments were performed every 3 months using cystoscopy, biopsy if necessary, and urine cytology.

The results were impressive:

• Of the 223 patients eligible for response assessment, 78% (95% CI: 72–83) at month 3 achieved a complete response to treatment.
• Of the patients who achieved this complete response, 79%remained disease-free for at least 12 months afterward.
• The duration of response ranged from 0 to 25+ months.

Key safety findings: The most common (%≥10) adverse reactions were increased creatinine and potassium, burning during urination (dysuria), decreased hemoglobin, increased liver enzymes, eosinophilia, decreased lymphocyte counts, urinary tract infection, and hematuria.

• Serious adverse reactions occurred in 12%. One death due to cardiac failure was reported.

Why Is This an Important Development?

Approximately 70% of bladder cancers are non-muscle-invasive tumors. One of the main challenges in this group is the very high recurrence rate . Controlling recurrent disease and developing new treatment options are therefore highly valuable in clinical practice.

Zusduri offers a new intravesical treatment option for this patient group, particularly in recurrent, low-grade cases that have not responded to TURBT. A high complete response rate of 78% at month 3, with most responses lasting 1 year or longer, demonstrates its clinical effect.

What Other Approved Treatment Options Are Available?

The main alternative treatments approved by the FDA for patients with recurrent non-muscle-invasive bladder cancer are:

1. Intravesical BCG

This approach is considered standard first-line treatment, particularly for patients with high-risk bladder cancer. It generally begins with a 6-week induction (initial) treatment course, followed by maintenance therapy lasting 1 to 3 years .

However, low-grade, recurrent disease may not always warrant BCG as the first choice. Less toxic and better-tolerated alternatives can also be considered for these patients.

2. Gemcitabine + Docetaxel Combination

• Retrospective studies have shown effectiveness particularly in BCG-unresponsive patients.

3. Nadofaragene Firadenovec

This treatment works through a recombinant adenoviral vector administered into the bladder (see our related article on its 2022 FDA approval). This vector delivers the interferon alfa-2b gene to cells in the bladder wall, enabling local production of this immune-activating protein.

It has been found effective particularly in patients with carcinoma in situ (CIS) , with studies reporting complete response rates of up to 53% .

4. Nogapendekin Alfa Inbakisept (NAI) + BCG Combination

Nogapendekin alfa inbakisept (abbreviated NAI, also known as N-803) is a molecule that strongly activates the immune system as an IL-15 superagonist (see our article on its 2024 FDA approval). When used with BCG, it produces a stronger immune response against tumor cells in the bladder wall.

Studies particularly in patients with BCG-unresponsive carcinoma in situ (CIS) have shown that this combination can achieve complete response rates of up to 71% .

5. Pembrolizumab (Systemic Immunotherapy)

Pembrolizumab is an immune checkpoint inhibitor that acts as a PD-1 inhibitor. In bladder cancer, it has FDA approval particularly for patients who are BCG-unresponsive and decline or are ineligible for radical cystectomy .

In this group, systemic (intravenous) immunotherapy aims to achieve bladder preservation .

• Studies particularly in patients with carcinoma in situ (CIS) have reported a complete response rate of 41% .
• However, some responses are short-lived, and long-term effectiveness is lower.

Conclusion

Zusduri (intravesical mitomycin gel) is an important new treatment option for patients with intermediate-risk non-muscle-invasive bladder cancer. Its high efficacy and acceptable adverse reaction profile offer promise for controlling recurrent disease in this group. However, individualized, risk-adapted approaches should remain the priority for every patient.

It is important to discuss this development and the other treatment options in detail with your doctor.