SUMMARY

• INLEXZO (gemcitabine intravesical system) is an intravesical drug releasing system (iDRS), referred to as TAR-200 in literature.​¹ 
• No prospective, randomized, head-to-head trials study comparing the efficacy and safety of INLEXZO to gemcitabine or gemcitabine/docetaxel have been conducted.
• Alternative Formats of Information
  • A video summary of Daneshmand et al (2024)² can be accessed in the following link:
    • Video: Poster Summary: Project Penelope
• Daneshmand et al (2024)² presented results of Project Penelope, a preclinical study that compared the penetration, retention, and tissue distribution of gemcitabine and its active metabolites (diphosphate and triphosphate of gemcitabine) with INLEXZO vs traditional intravesical instillation methods in minipigs (N=5).
  • Elevated concentrations of gemcitabine diphosphate and triphosphate were observed across all bladder layers 2 hours after treatment with intravesical instillation.
  • With INLEXZO, gemcitabine diphosphate and triphosphate concentrations were sustained in all bladder tissue layers for up to 96 hours.
  • With INLEXZO, higher gemcitabine diphosphate and triphosphate concentrations were maintained in the urothelium and lamina propria than those in the muscle.
• SunRISe-5 (NCT06211764) is a phase 3, randomized, open-label, multicenter study that aims to evaluate the efficacy and safety of INLEXZO vs the investigator’s choice of intravesical chemotherapy (mitomycin C or gemcitabine) in patients with recurrent, papillary-only high-risk non-muscle-invasive bladder cancer (NMIBC) who have received Bacillus Calmette-Guérin (BCG) therapy and have refused or are ineligible for radical cystectomy (RC). Enrollment is planned for approximately 250 patients. The primary endpoint is disease-free survival (DFS).^3,4
  • As of November 5, 2024, 98% (~120) of the sites have been activated and 42% (105/250) of the target population has been randomized.⁵ 

Product labeling

• INLEXZO (gemcitabine intravesical system) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/INLEXZO-pi.pdf.
• INLEXZO (gemcitabine intravesical system) [Instructions for Use]. Horsham, PA: Janssen Biotech, Inc; https://www.janssenlabels.com/package-insert/product-instructions-for-use/INLEXZO-ifu.pdf.

PRECLINICAL DATA

Project Penelope

Daneshmand et al (2024)² compared the penetration, retention, and tissue distribution of gemcitabine and its active metabolites (diphosphate and triphosphate of gemcitabine) with INLEXZO vs traditional intravesical instillation methods in minipigs (N=5).

Study Design/Methods

• Three minipigs were treated with intravesical gemcitabine instillation, and 2 minipigs were treated with INLEXZO.
• All minipigs were assessed for penetration of active gemcitabine metabolites across different tissues of the bladder wall for over 96 hours.
• Collected samples included the dome (urothelium and lamina propria), left and right lateral wall, and trigone. Processed samples were analyzed for gemcitabine and its active metabolites using liquid chromatography tandem mass spectrometry (LC-MS/MS).
• The 3 minipigs receiving intravesical gemcitabine instillation were administered a 50 mL solution containing 2 g of freebase equivalent of gemcitabine hydrochloride (dissolved in saline at 40 mg/mL) via a Foley balloon catheter for 2 hours.
• The 2 minipigs receiving INLEXZO were administered 225 mg of freebase equivalent of gemcitabine. INLEXZO was inserted directly into the bladder, and was left in place for the duration of the study until necropsy.
• Tissue samples were collected at necropsy at different time intervals after instillation (animal 1, 2 hours; animal 6, 24 hours; animal 5, 96 hours) and INLEXZO insertion (animal 4, 48 hours; animal 3, 96 hours). See Figure: Treatment Administration Schedule for Minipigs.

Results

Intravesical Gemcitabine Instillation

• Elevated concentrations of gemcitabine diphosphate and triphosphate were observed across all bladder layers (urothelium, lamina propria, and muscle) 2 hours after treatment. The mean concentrations of active metabolites in bladder tissue layers decreased to below 1 ng/g by 24 hours; see Figure: Mean Concentrations of Gemcitabine Active Metabolites in Bladder Tissue Layers After Intravesical Gemcitabine Instillation.

INLEXZO

• With INLEXZO treatment, gemcitabine diphosphate and triphosphate levels were detectable in all bladder tissue layers during the 48- and 96-hour indwelling periods; see Figure: Mean Concentrations of Gemcitabine Active Metabolites in Bladder Tissue Layers After Treatment With INLEXZO.
• Active metabolite concentrations were higher in the urothelium and lamina propria than in the muscle; the concentrations remained high for up to 96 hours in both tissue samples.
• Active metabolite concentrations were lower than those observed 2 hours after gemcitabine instillation but were sustained across all bladder tissues for up to 96 hours.

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 19 August 2025.