INLEXZO - Comparison to Intravesical Gemcitabine and Gemcitabine/Docetaxel

SUMMARY

• INLEXZO (gemcitabine intravesical system) is an intravesical drug releasing system (iDRS), referred to as TAR-200 in literature.​¹ 
• 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).^2,3
  • As of November 5, 2024, 98% (~120) of the sites have been activated and 42% (105/250) of the target population has been randomized.⁴
• Kulkarni et al (2026)⁵ evaluated the relative effectiveness of INLEXZO vs real-world intravesical chemotherapies (IVEC), including gemcitabine monotherapy and gemcitabine-docetaxel combination therapy, using a hypothesis‑generating indirect treatment comparison (ITC), in patients with BCG‑unresponsive high-risk NMIBC with carcinoma in situ (CIS).
  • INLEXZO was associated with higher odds (odds ratios [OR]) of achieving a complete response (overall CR at any time) compared with real-world IVECs (adjusted OR, 13.54; 95% confidence interval [CI], 7.24-31.17).
  • The median event-free survival (EFS) with INLEXZO vs real-world IVECs was 12.6 months and 3.7 months, respectively (adjusted hazard ratio [HR], 0.41; 95% CI, 0.23-0.55).
• Daneshmand et al (2026)⁶ evaluated the penetration, tissue distribution, and retention of gemcitabine and its active metabolites (gemcitabine diphosphate [dFdCDP] and gemcitabine triphosphate [dFdCTP]) in Penelope, a preclinical study comparing INLEXZO with traditional intravesical instillation methods in healthy minipigs (N=5).
  • 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]).
• Alternative Formats of Information
  • A video summary of Daneshmand et al (2024)⁷ can be accessed in the following link:
    • Video: Poster Summary: Project Penelope

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.

Indirect Treatment Comparison Data

Kulkarni et al (2026)⁵ evaluated the relative effectiveness of INLEXZO vs real-world IVECs, including gemcitabine monotherapy and gemcitabine-docetaxel combination therapy, using a hypothesis‑generating ITC, in patients with BCG‑unresponsive high-risk NMIBC with CIS.

Study Design/Methods

• Patient-level data from SunRISe1 cohort 2 (data cutoff: March 2025) were compared with chartreviewed data from patients with highrisk NMIBC with CIS treated with IVEC from the American Urological Association Quality (AQUA) Registry, linked to Komodo Health claims (data cutoff: December 2024).
  • Patients were identified based on receipt of adequate BCG (≥7 doses within 6 months) between 2015-2022 and initiation of IVEC within 1 year of adequate BCG for CIS recurrence.
• Endpoints included CR and EFS, aligned to the SunRISe-1 study definitions where corresponding variables were available in the AQUA registry.
  • CR was defined as normal cystoscopy, negative urine cytology or pathology, or physician documentation abstracted from unstructured clinical notes.
  • EFS was defined as the time from treatment initiation to persistent disease at first assessment, high‑risk recurrence, progression (≥T2 disease and/or metastasis), or death.
    • Recurrence was confirmed by positive transurethral resection of bladder tumor (TURBT) or biopsy showing high‑grade Ta, any T1, or CIS based on unstructured clinical notes.

Results

• The median follow-up duration was 20.2 months for INLEXZO SunRISe-1 cohort 2 and 31 months for the real-world IVEC cohort. Baseline characteristics are summarized in Table: Baseline Characteristics (Unadjusted).

CR

• The overall CR rate (at any time) for all real-world IVECs was 26.1% (35/134).
  • The overall CR rates (at any time) for gemcitabine monotherapy and gemcitabine-docetaxel combination therapy were 22.5% (9/40) and 40% (8/20), respectively.
• INLEXZO was associated with higher odds (ORs) of achieving a complete response (overall CR at any time) compared with real-world IVECs (see table: Adjusted ORs of Overall CR (at any time) with INLEXZO vs Real-World IVECs).

EFS

• The median EFS with INLEXZO vs real-world IVECs was 12.6 months and 3.7 months, respectively.
  • INLEXZO demonstrated a 59% risk reduction (adjusted HR, 0.41; 95% CI, 0.23-0.55) compared with real-world IVECs.
  • After inverse probability treatment weighting (IPTW) adjustment, INLEXZO demonstrated a 57% risk reduction (adjusted HR, 0.43; 95% CI, 0.3-0.61) compared with real-world IVECs.
• The median EFS with INLEXZO vs gemcitabine monotherapy was 12.6 months and 3.7 months, respectively.
  • INLEXZO showed a 74% risk reduction (adjusted HR: 0.26; 95% CI, 0.09-0.47) compared with gemcitabine monotherapy.
• The median EFS with gemcitabine-docetaxel combination therapy was 4 months. The sample size was too small for a statistical comparison with INLEXZO.

PRECLINICAL DATA

Penelope Study

Daneshmand et al (2026)⁶ 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.^6,8 
  • 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.⁸ 
  • 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.⁸ 
• The 2 minipigs receiving INLEXZO were administered 225 mg of freebase equivalent of gemcitabine.⁶ INLEXZO was inserted directly into the bladder, which was left in place for the duration of the study until necropsy.^6,8 
  • Tissue samples were collected at necropsy at different time intervals after INLEXZO insertion (animal 4, 48 hours; animal 3, 96 hours).⁸

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 (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.⁸ 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.⁶ 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 11 May 2026.