UroGen's ZUSDURI Shows Long-Term Efficacy in Non-Muscle Invasive Bladder Cancer

Analysis reveals significant industry trends and economic implications

Release Date

2025-07-22

Category

Clinical Trial Event

Reference

Source

Breakthrough Clinical Results

UroGen Pharma announced the publication of five-year long-term extension study results from the Phase 2b OPTIMA II trial. The study evaluated ZUSDURI (mitomycin) intravesical solution in patients with low-grade intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC). Results demonstrated durable, long-term complete responses (CRs) in patients who initially achieved a CR following treatment with ZUSDURI. The median duration of response was 3.5 years for patients in the long-term extension study. This non-surgical approach offers a valuable alternative for recurrent patients, providing a sustained response in an outpatient setting.

Key Highlights

  • Five-year long-term extension study of OPTIMA II trial demonstrates durable, long-term complete responses with ZUSDURI in LG-IR-NMIBC patients.
  • Median duration of response was 3.5 years in the long-term extension study.
  • ZUSDURI offers a non-surgical treatment option for recurrent LG-IR-NMIBC patients.
  • Results published in the journal of Clinical Genitourinary Cancer.

Incidence and Prevalence

Global Estimates of Non-muscle Invasive Bladder Cancer

Bladder cancer is approximately the fourth most prevalent diagnosed cancer in men and is three times less common in women. According to the most recent data (from 2023), bladder cancer is the 9th most frequent cancer worldwide.

Non-muscle invasive bladder cancer (NMIBC) represents a significant portion of bladder cancer cases. Based on available data, bladder cancer affects approximately 420,000 new cases and causes 160,000 deaths per year globally (as reported in a 2020 publication).

NMIBC is clinically and genetically a highly heterogeneous disease characterized by its high rate of disease recurrence and relevant disease progression rates. It accounts for a significant portion of urinary tract cancers, while Upper tract urothelial carcinoma (UTUC) accounts for 5-10% of urinary tract cancers (as reported in a 2023 publication).

A 2023 study examining socioeconomic characteristics in NMIBC management included 163,949 patients, with 64% having Ta disease, 32% with T1, and 4% with Tis disease. This distribution provides insight into the typical presentation patterns of NMIBC.

Demographic and socioeconomic factors appear to influence disease presentation. Among patients diagnosed with bladder cancer, male patients (OR 1.24, 95%CI 1.21-1.27), uninsured patients (OR 1.10, 95%CI 1.01-1.19 vs. private), and non-White patients (OR 1.34, 95%CI 1.28-1.41 for Black; OR 1.10; 95%CI 1.03-1.18 for Other vs. White) were more likely to be diagnosed with high-risk disease. Additionally, patients from lower education level areas were also more likely to be diagnosed with high-risk disease.

In terms of mortality patterns, NMIBC patients differ from those with muscle-invasive and metastatic bladder cancer. In one study, 44,638 NMIBC patients died during follow-up, including 20.57% of bladder cancer, 18% of other tumors and 61.36% of non-tumor diseases. Leading causes of death were diseases of heart, COPD, lung and bronchus cancer, cerebrovascular diseases, Alzheimer's, and diabetes mellitus.

It's worth noting that inverted papilloma of the urothelium accounts for 2.2% of urothelial neoplasms.

Current clinical models are insufficiently predicting outcomes for reliable patient counseling and treatment decision-making in NMIBC. There is an essential need of biomarkers for improving clinical staging, real-time monitoring of disease, and improved outcome prognostication, particularly for high-risk NMIBC patients who are at elevated risk for failure of local treatment.

Non-muscle invasive bladder cancer (NMIBC) represents a significant challenge in urological oncology due to its high recurrence rates and potential for progression to muscle-invasive disease. Recent PubMed publications highlight several key unmet needs and target populations within NMIBC:

  • Improved Risk Stratification: Current risk stratification methods, while helpful, are imperfect. There's a need for more precise tools to identify patients at highest risk of recurrence and progression, allowing for more tailored and effective treatment strategies. This includes exploring novel biomarkers, molecular signatures, and imaging techniques to enhance risk prediction.

  • Optimizing Bacillus Calmette-Guerin (BCG) Therapy: BCG remains the gold standard intravesical immunotherapy for intermediate- and high-risk NMIBC. However, a substantial proportion of patients do not respond adequately, and others experience recurrence after initial success. Research focuses on optimizing BCG delivery (e.g., dose, frequency, strain), developing strategies to predict and overcome BCG resistance, and exploring combination therapies with BCG to enhance efficacy.

  • Alternatives to BCG: Given the limitations and potential side effects of BCG, there's a significant need for effective alternative therapies, especially for BCG-unresponsive or intolerant patients. Research explores novel immunotherapies (e.g., checkpoint inhibitors, oncolytic viruses), targeted therapies, and chemotherapy regimens delivered intravesically or systemically.

  • Reducing Recurrence Rates: NMIBC is characterized by high recurrence rates, even after successful initial treatment. This necessitates frequent cystoscopic surveillance, which is burdensome for patients and healthcare systems. Research aims to develop strategies to reduce recurrence rates, including novel therapies, lifestyle modifications, and chemoprevention strategies.

  • Minimizing Morbidity from Treatment and Surveillance: Current treatments and surveillance strategies for NMIBC can be associated with significant morbidity, including bladder irritation, pain, and infections. Research focuses on developing less invasive and more tolerable treatment and surveillance modalities, such as improved cystoscopic techniques, urine-based biomarkers, and less toxic therapies.

  • Personalized Medicine: The heterogeneity of NMIBC underscores the need for personalized medicine approaches. Research aims to identify molecular subtypes and biomarkers that can predict response to specific therapies, allowing for more tailored and effective treatment strategies.

  • Improving Patient-Reported Outcomes: Beyond clinical outcomes, there's increasing emphasis on improving patient-reported outcomes, such as quality of life, symptom burden, and treatment satisfaction. Research explores the impact of different treatment and surveillance strategies on these important aspects of patient care.

Target populations within NMIBC that are receiving particular attention include:

  • BCG-unresponsive patients: This group represents a significant unmet need, as there are limited effective treatment options after BCG failure.

  • Patients with high-grade T1 tumors: These tumors have a higher risk of progression to muscle-invasive disease and require aggressive treatment and close surveillance.

  • Patients with variant histology: Certain histologic subtypes of NMIBC, such as carcinoma in situ and micropapillary carcinoma, are associated with worse prognosis and require specific management strategies.

  • Older adults: This population often has comorbidities that can complicate treatment and surveillance, and there's a need for age-appropriate management strategies.

Addressing these unmet needs and focusing on these target populations will be crucial for improving the outcomes and quality of life for patients with NMIBC.

Drug used in other indications

Indications for ZUSDURI (Mitomycin) Beyond Non-muscle Invasive Bladder Cancer

Based on the available information, there is no specific evidence that ZUSDURI (mitomycin) is currently being trialed for indications beyond Non-muscle invasive bladder cancer (NMIBC).

While mitomycin has been used in various applications related to urological cancers, including:

  • Treatment of bladder cancer (both muscle-invasive and non-muscle invasive)
  • Upper tract urothelial carcinoma (a novel mitomycin formulation was approved for this indication)
  • In combination with suramin for enhancing chemosensitivity in bladder cancer
  • Compared with bacillus Calmette-Guérin (BCG) for treating high-risk bladder cancer

There is no clear indication that ZUSDURI specifically is being investigated in clinical trials for conditions beyond NMIBC.

Other Cancer Treatments Being Investigated

While not directly related to mitomycin/ZUSDURI, research is ongoing for treatments of other cancers such as Medullary Thyroid Carcinoma (MTC) with:

  1. Sunitinib: A potent inhibitor of RET, VEGF receptors (VEGFR-1, VEGFR-2, VEGFR-3), and platelet-derived growth factor receptors (PDGFRα/β)

  2. Vandetanib: A VEGF and EGF receptor inhibitor that blocks RET tyrosine kinase activity

Intervention Models for MTC Trials

Although not related to mitomycin, the following intervention models are being used in MTC trials:

For Sunitinib:

  • In vitro and in vivo assays using the human TT RET(C634W) MTC cell line
  • Kinetic microarray studies to analyze molecular pathways and identify biomarkers

For Vandetanib:

  • Phase I/II trial for children (5-12 years) and adolescents (13-18 years) with MTC
  • Oral administration at 100 mg/m² once daily, continuously for 28-day treatment cycles
  • Dose could be escalated to 150 mg/m²/d after two cycles
  • Radiographic response measured using RECIST (v1.0)
  • Biomarker response measured by comparing posttreatment serum calcitonin and carcinoembryonic antigen (CEA) levels to baseline
  • Patient-reported outcome used to assess clinical benefit

In summary, while mitomycin continues to be an important treatment for bladder cancer and some related urological malignancies, the available information does not indicate that ZUSDURI is currently being investigated in clinical trials for indications beyond non-muscle invasive bladder cancer.