INLEXZO - Publication Summary: Daneshmand et al (2026) - Penelope

SUMMARY

• INLEXZO (gemcitabine intravesical system) is an intravesical drug releasing system (iDRS), referred to as gem-iDRS and TAR-200 in literature.¹
• Alternative Formats of Information
  • A summary of the information provided in this response is provided as a video that can be accessed by clicking the following link:
    • Video: INLEXZO - Poster Summary: Project Penelope² 
• Penelope was a preclinical study that compared the penetration, tissue distribution, and retention of gemcitabine and its active metabolites (gemcitabine diphosphate [dFdCDP] and gemcitabine triphosphate [dFdCTP]) with INLEXZO vs traditional intravesical instillation methods in healthy minipigs (N=5).³ 
  • Concentrations of dFdCDP and dFdCTP were detected across all bladder layers 2 hours after intravesical instillation. 
  • With INLEXZO, metabolite concentrations were sustained across all bladder tissue layers for up to 96 hours, with urothelium/lamina propria dFdCDP levels of 20.8-75.5 ng/g (48 hours) and 15-134 ng/g (96 hours) and dFdCTP levels of 7.34-27.0 ng/g and 11.6-134 ng/g, respectively. 
  • With INLEXZO, metabolite concentrations were consistently higher in the urothelium and lamina propria than in the muscle (dFdCTP levels: range, 2.39-3.45 ng/g [48 hours] and 2.29-8.66 ng/g [96 hours]). 

Product labeling

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

PRECLINICAL DATA

Penelope Study

Daneshmand et al (2026)³ compared the penetration, tissue distribution and retention of gemcitabine and its active metabolites (dFdCDP and dFdCTP) with INLEXZO vs traditional intravesical instillation methods in minipigs (N=5).

Study Design/Methods

• This evaluation was done in an animal model because clinical studies cannot directly characterize the duration or depth of gemcitabine penetration within bladder tissue.
• Three healthy female minipigs received intravesical gemcitabine instillation, and 2 healthy female minipigs received INLEXZO.
• All minipigs were assessed for penetration of active gemcitabine metabolites across different tissues of the bladder wall for over 96 hours.
• Collected bladder tissue 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.^3,4
  • Following intravesical instillation of 2 g gemcitabine and 2 hours exposure of the instilled formulation, the Foley balloon catheter was removed, and complete urine and instillation fluid were collected.⁴ 
  • Tissue samples were collected from animal 1 at 2 hours (end of the instillation period) and from animal 6 at 24 hours and animal 5 at 96 hours.⁴ 
• The 2 minipigs receiving INLEXZO were administered 225 mg of freebase equivalent of gemcitabine.³ INLEXZO was inserted directly into the bladder, which was left in place for the duration of the study until necropsy.^3,4 
  • Tissue samples were collected at necropsy at different time intervals after INLEXZO insertion (animal 4, 48 hours; animal 3, 96 hours).⁴

Results

Intravesical Gemcitabine Instillation

• Average bladder gemcitabine concentrations were detected across all bladder regions at 2 hours and were 5.5 ng/g at 24 hours and 38.6 ng/g at 96 hours.
• Active metabolite concentrations were detected in all bladder regions and layers at 2 hours with dFdCDP levels (urothelium/lamina propria, 1260–4950 ng/g; muscle, 268–630 ng/g) and dFdCTP levels (urothelium/lamina propria, 272–1550 ng/g; muscle, 109–278 ng/g), representing 0.02–0.25% of the gemcitabine tissue concentrations.
• By 24 hours and 96 hours, the concentrations of active metabolites were virtually undetectable.
• Urine/instillation fluid concentrations at 2 hours after the indwelling period were 13.1 mg/ml and 0.0648 mg/ml for gemcitabine and its metabolite, 2´,2´­diflurodeoxyuridine (dfdU), respectively.
• Urine gemcitabine concentrations at 2 hours after the indwelling period in 2 minipigs were 9700 µg/ml and 8000 µg/ml, but declined over time, reaching 2400 µg/ml at 24 hours and 3.84 µg/ml at 96 hours.

INLEXZO

• With INLEXZO treatment, average bladder gemcitabine concentrations were 3140 ng/g (48 hours) and 3853 ng/g (96 hours).
• Active metabolites, dFdCDP and dFdCTP, were detected in all bladder tissue layers at 48 hours and 96 hours.
  • At 48 hours and 96 hours, dFdCDP levels ranged from 20.8–75.5 ng/g and 15-134 ng/g in the urothelium/lamina propria, respectively.⁴ At both time points, dFdCTP levels in the muscle were below the levels of quantification.
  • At 48 hours, dFdCTP levels ranged from 7.34-27.0 ng/g in the urothelium/lamina propria and 2.39-3.45 ng/g in the muscle.³ At 96 hours, dFdCTP levels ranged from 11.6-134 ng/g and 2.29-8.66 ng/g, respectively.
• Average urine gemcitabine concentrations of about 5 μg/ml were achieved by 24 hours and remained above this level through 96 hours, with maximum urine gemcitabine concentrations at 48-72 hours ranging from 30.8-33.6 µg/ml.
• Recovered INLEXZO devices at necropsy contained 180 mg (80% from the theoretical initial amount of 225 mg) and 81.9 mg (36.4%) at 48 and 96 hours.
• Residual dFdU was below the lower limit of quantification.

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 26 March 2026.