Gemcitabine Intravesical System (Inlexzo)

Number: 1095

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

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Policy

Scope of Policy

This Clinical Policy Bulletin addresses gemcitabine intravesical system (Inlexzo) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

Note: Requires Precertification:

Precertification of gemcitabine intravesical system (Inlexzo) is required of all Aetna participating providers and members in applicable plan designs. For precertification of gemcitabine intravesical system (Inlexzo), call (866) 752-7021 or fax (888) 267-3277. For Statement of Medical Necessity (SMN) precertification forms, see Specialty Pharmacy Precertification.

1. Criteria for Initial Approval

   Aetna considers gemcitabine intravesical system (Inlexzo) medically necessary for the treatment of Bacillus Calmette-Guérin (BCG)-unresponsive, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), with or without papillary tumors when all of the following criteria are met:

   1. The requested drug will be used as a single agent inserted intravesically; and
   2. The requested drug will be given once every 3 weeks for up to 6 months, followed by once every 12 weeks for up to 18 months.

   Aetna considers all other indications as experimental, investigational, or unproven.

2. Continuation of Therapy

   Aetna considers continuation of gemcitabine intravesical system (Inlexzo) therapy (up to a total of 14 doses) medically necessary for treatment in members requesting reauthorization for an indication listed in the Criteria for Initial Approval section when there is no evidence of persistent or recurrent NMIBC, disease progression, or unacceptable toxicity while on the current regimen.

Dosage and Administration

Gemcitabine intravesical system is supplied as Inlexzo and available as one single-dose 225 mg gemcitabine intravesical system for intravesical administration only. Do not administer by any other route. Inlexzo should be inserted and removed by a trained healthcare provider.

• Insert Inlexzo (225 mg of gemcitabine) into the bladder once every 3 weeks up to 6 months (8 doses), followed by once every 12 weeks (6 doses).
• Insert into the bladder using the co-packaged urinary catheter and stylet only.
• Remove Inlexzo after each 3-week indwelling period.
• Inlexzo is co-packaged with a urinary catheter and stylet used to insert Inlexzo through the urinary catheter into the bladder.
• Administer using the co-packaged urinary catheter and stylet only.
• Refer to full prescribing information and instructions for use for insertion and removal procedures.

Source: Janssen Biotech, 2025

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
CPT codes covered if selection criteria are met:
Gemcitabine Intravesical System (Inlexzo)- no specific code
Other CPT codes related to the CPB:
51720	Bladder instillation of anticarcinogenic agent (including retention time)
52310	Cystourethroscopy, with removal of foreign body, calculus, or ureteral stent from urethra or bladder (separate procedure); simple
52315	complicated
90586	Bacillus Calmette-Guerin vaccine (BCG) for bladder cancer, live, for intravesical use
HCPCS codes covered if selection criteria are met:
J9183	Gemcitabine intravesical system, 225 mg
Other HCPCS codes related to the CPB:
J9030	BCG live intravesical instillation, 1 mg
ICD-10 codes covered if selection criteria are met:
C67.0 – C67.9	Malignant neoplasm of bladder
D09.0	Carcinoma in situ of bladder

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Background

U.S. Food and Drug Administration (FDA)-Approved Indications 

• Inlexzo is indicated for the treatment of adult patients with Bacillus Calmette-Guérin (BCG)-unresponsive, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), with or without papillary tumors.

Gemcitabine intravesical system is available as Inlexzo (Janssen Biotech, Inc.). The Inlexzo intravesical system contains gemctiabine hydrochloride, a nucleoside metabolic inhibitor. Gemcitabine kills cells engaged in DNA synthesis and blocks their progression through the G1/S phase. Once gemcitabine is metabolized by nucleoside kinases, it forms diphosphate (dFdCDP) and triphosphate (dFdCTP) nucleosides. Gemcitabine diphosphate suppresses ribonucleotide reductase, an enzyme that produces deoxynucleoside triphosphates necessary for DNA synthesis, leading to a decrease in deoxynucleotide concentrations, such as dCTP. Meanwhile, gemcitabine triphosphate competes with dCTP for integration into DNA strands. The reduced dCTP levels, resulting from the diphosphate’s action, facilitate the incorporation of gemcitabine triphosphate into DNA, thereby enhancing its own activity. Once the gemcitabine nucleotide is incorporated into DNA, the addition of only one further nucleotide to the growing DNA strands eventual results in triggering apoptotic cell death (Janssen Biotech, 2025).

According the prescribing information, Inlexzo carries the following information about contraindications, warnings and precautions, adverse reactions, and use in specific populations:

• Contraindications:

  • Perforation of the bladder
  • Prior hypersensitivity reaction to gemcitabine or any component of the
    product.
    
    

• Warnings and precautions:

  • Risks in patients with perforated bladder: Evaluate the bladder before the intravesical insertion of Inlexzo. Do not administer to patients with a perforated bladder or in whom the integrity of the bladder mucosa has been compromised.
  • Risk of metastatic bladder cancer with delayed cystectomy: Delaying cystectomy can lead to the development of metastatic bladder cancer, which can be lethal.
  • Magnetic resonance imaging (MRI) safety: Inlexzo can only be safely scanned with MRI under certain conditions.
  • Embryo-fetal toxicity: Can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception.
    
    

• Adverse reactions:

  The most common (>15%) adverse reactions, including laboratory abnormalities, are urinary frequency, urinary tract infection, dysuria, micturition urgency, decreased hemoglobin, increased lipase, urinary tract pain, decreased lymphocytes, hematuria, increased creatinine, increased potassium, increased AST, decreased sodium, bladder irritation, and increased ALT. 

• Use in specific populations:

  Lactation: Advise not to breastfeed.

On September 9, 2025, the U.S. Food and Drug Administration (FDA) approved the gemcitabine intravesical system (Inlexzo) for use in adult patients with Bacillus Calmette-Guérin (BCG)-unresponsive non–muscle invasive bladder cancer (NMIBC) presenting with carcinoma in situ (CIS), with or without papillary tumors. Inlexzo is supplied with a urinary catheter and a stylet, specifically designed for its insertion into the bladder. The FDA approval was based on supporting data from Cohort 2 of the SunRISe-1 trial (NCT04640623) (FDA, 2025).

Investigators evaluated the efficacy of gemcitabine intravesical system (Inlexzo) in Cohort 2 of the SunRISe-1 trial (NCT04640623), a single-arm, multicenter study that enrolled 83 patients with BCG-unresponsive NMIBC with CIS, with or without papillary tumors, after undergoing transurethral resection of bladder tumor (TURBT) to remove all resectable disease (Ta and T1 components). Patients received Inlexzo (225 mg of gemcitabine) into the bladder every three weeks for six months, followed by once every 12 weeks over an 18-month period, or until unacceptable toxicity, persistence or recurrence of CIS and/or high-grade papillary disease, or progression. The investigators conducted tumor assessments every 12 weeks during the initial two years using cystoscopy and urine cytology, with subsequent cystoscopic evaluations scheduled at least every 24 weeks. Additionally, biopsies were mandatorily performed at 24 and 48 weeks after treatment initiation (FDA, 2025; Janssen Biotech, 2025).

The primary efficacy endpoints were the complete response (CR) at any time (defined as a negative cystoscopy [with TURBT/biopsies as applicable) and a negative urine cytology] and the duration of response (DOR). CR was confirmed by central pathology review. The study reported a CR rate of 82% (95% confidence interval [CI]: 72, 90), with 51% (35) of responders maintaining a DOR of 12 months or longer (FDA, 2025; Janssen Biotech, 2025).

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References