Regulatory Decision Summary for Adstiladrin

This New Drug Submission (NDS) was filed to obtain market authorization for Adstiladrin (nadofaragene firadenovec) for the following indication:

Adstiladrin (nadofaragene firadenovec) is indicated for:

• Treatment of adult patients with high-grade Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC).

After review of the submission, Health Canada authorized the following indication:

Adstiladrin (nadofaragene firadenovec) is indicated for:

• Treatment of adult patients with Bacillus Calmette-Guérin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumours.

Non-muscle-invasive bladder cancer (NMIBC) accounts for roughly 75% of newly diagnosed cases of bladder cancer. NMIBC generally has a good prognosis but is associated with high recurrence rates with the potential for tumours to progress to muscle-invasive disease, which has a high mortality rate. In patients with high-risk NMIBC, treatment with Bacillus Calmette-Guérin (BCG) is the standard of care for reducing risk of disease recurrence and progression rates following transurethral resection of bladder tumour (TURBT). Patients who become unresponsive to BCG therapy have limited effective treatment options outside of radical cystectomy, which is associated with significant risks including a considerable negative impact on quality of life and significant perioperative morbidity. Thus, additional bladder-sparing treatment options are needed for this patient population.

Adstiladrin is a non-replicating adenoviral vector-based gene therapy containing the human interferon alpha 2b (IFNα2b) transgene. Intravesical administration of Adstiladrin results in transduction of urothelial cells and transient local expression and secretion of the IFNα2b protein that is anticipated to have anti-tumour effects.

The safety and efficacy of Adstiladrin were evaluated in CS-003, an open-label, single arm, multicenter trial in adult patients with BCG-unresponsive NMIBC. Adstiladrin provided a clinically meaningful complete response rate of 53.4% (95% confidence interval [CI]: 43.3, 63.3) with a median duration of response of 9.7 months (95% CI: 9.17, 23.95) in patients with CIS with or without papillary tumours.

The safety profile of Adstiladrin is generally consistent with its mechanism of action and the method of administration resulting in a primarily bladder-localized safety profile with limited systemic effects. Adverse reactions were generally mild to moderate in severity and transient. The rate of progression to muscle invasive disease was generally consistent with historical rates in patients delaying cystectomy for other bladder-sparing treatment options. The risks of treatment with Adstiladrin can be mitigated and managed through labelling in the Product Monograph and through routine post-market pharmacovigilance activities.

Overall, the benefit-risk profile was considered favourable for Adstiladrin for the authorized indication when used under the conditions of use recommended in the approved Product Monograph. Therefore, a Notice of Compliance (NOC) was recommended.

A Risk Management Plan for Adstiladrin was reviewed by Health Canada and considered acceptable. The Core Risk Management Plan (RMP) version 0.1, dated November 20, 2024, and Canadian Addendum v1.0 dated January 31, 2025 and v2.0 dated January 6, 2026, for Adstiladrin were submitted to Health Canada as part of the New Drug Submission. The RMP is designed to describe known and potential safety issues, to present the monitoring plan and when needed, to describe measures that will be put in place to minimize risks associated with the product. Upon review, the RMP is considered to be acceptable and identified appropriate monitoring (pharmacovigilance) activities and risk minimization measures for Adstiladrin. This includes providing information in the product monograph and identifying populations and areas where more data is needed. Results related to the safety and effectiveness of Adstiladrin from post market use will be submitted in Periodic Benefit-Risk Evaluation Reports (PBRERs) as they become available.

The chemistry and manufacturing information submitted in support of Adstiladrin indicated that the drug substance and drug product can be consistently manufactured to meet the approved specifications.

The labelling material submitted met all applicable regulations and guidance.

For further details about Adstiladrin, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.

For further details about Adstiladrin (nadofaragene firadenovec), please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.