SUMMARY

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  • A summary of the information provided in this response is provided as a video that can be accessed by clicking the following link:
    • Video: TAR-200 - Poster Summary: Project Penelope
    • Credentials to access the webpage content: username, admin; password, janssen.sc1ence
• Daneshmand et al (2024)¹ 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 TAR-200 vs traditional intravesical instillation methods in minipigs (N=5).
  • Elevated concentrations of gemcitabine diphosphate and triphosphate were observed across all bladder layers 2 hours (h) after treatment with intravesical instillation. See Figure: Mean Concentrations of Gemcitabine Active Metabolites in Bladder Tissue Layers After Intravesical Instillation.
  • With TAR-200, gemcitabine diphosphate and triphosphate concentrations were sustained in all bladder tissue layers for up to 96 h. See Figure: Mean Concentrations of Gemcitabine Active Metabolites in Bladder Tissue Layers After Treatment With TAR-200.
  • With TAR-200, higher gemcitabine diphosphate and triphosphate concentrations were maintained in the urothelium and lamina propria than in the muscle.

BACKGROUND

• TAR-200 (JNJ-17000139) is an investigational intravesical system that is designed to provide local release of gemcitabine in the bladder. TAR-200 contains gemcitabine and urea mini tablets within a dual-lumen silicone tube for gradual release of gemcitabine by an osmotic delivery mechanism throughout the prescribed indwelling period.^1-5 
• TAR-200 is inserted intravesically via a urinary placement catheter, after which it self-coils into a bi-oval shape (see Figure: TAR-200 Intravesical System). Removal of TAR-200 can be achieved using grasping forceps and flexible cystoscopy.⁴

PRECLINICAL DATA

Project Penelope

Daneshmand et al (2024)¹ compared the penetration, retention, and tissue distribution of gemcitabine and its active metabolites (diphosphate and triphosphate of gemcitabine) with TAR-200 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 TAR-200.
• All minipigs were assessed for penetration of active gemcitabine metabolites across different tissues of the bladder wall for over 96 h.
• 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 grams (g) of freebase equivalent of gemcitabine hydrochloride (dissolved in saline at 40 mg/mL) via a Foley balloon catheter for 2 h.
• The 2 minipigs receiving TAR-200 were administered 225 mg of freebase equivalent of gemcitabine. The TAR-200 intravesical system was inserted directly into the bladder, which 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 h; animal 6, 24 h; animal 5, 96 h) and TAR-200 insertion (animal 4, 48 h; animal 3, 96 h), respectively. 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 h after treatment. Mean concentrations of active metabolites in bladder tissue layers decreased to below 1 ng/g by 24 h; see Figure: Mean Concentrations of Gemcitabine Active Metabolites in Bladder Tissue Layers After Intravesical Gemcitabine Instillation.

TAR-200

• With TAR-200 treatment, gemcitabine diphosphate and triphosphate levels were detectable in all bladder tissue layers during the 48 h and 96 h indwelling period; see Figure: Mean Concentrations of Gemcitabine Active Metabolites in Bladder Tissue Layers After Treatment With TAR-200.
• Active metabolite concentrations were higher in the urothelium and lamina propria than in the muscle and remained for up to 96 h in both tissue samples.
• Active metabolite concentrations were lower than those observed 2 h after gemcitabine instillation but were sustained across all bladder tissues for up to 96 h.

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 27 November 2024.