Nadofaragene Firadenovec Showcases Sustained Responses in BCG-Unresponsive NMIBC


The intravesical gene therapy elicited durable remissions in a high percentage of patients with high-risk, BCG-unresponsive non–muscle invasive bladder cancer.

Colin PN Dinney, MD

Colin PN Dinney, MD

Extended treatment with nadofaragene firadenovec-vncg (Adstiladrin) proved tolerable and led to prolonged remission in patients with high-risk, BCG-unresponsive non–muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) or papillary disease, according to 3-year follow-up data from a phase 3 trial (NCT02773849).1,2

In efficacy-evaluable patients with CIS with or without a high-grade Ta or T1 tumor (CIS cohort; n = 103), about 53.4% (95% CI, 43.3%-63.3%) achieved a complete response (CR) at 3 months in the primary analysis.3 At 3 years, approximately 25% of these patients (n = 14/55) remained free from high-grade recurrence. In a secondary analysis, approximately 72.9% (n = 35) of efficacy-evaluable patients with high-grade papillary disease and without CIS (papillary cohort; n = 48) were free from high-grade recurrence at 3 months and of these patients, 31.4% (n = 11) remained free of high-grade recurrence through 3 years.

“While radical cystectomy provides excellent cancer control for NMIBC patients who no longer respond to standard therapy, most are elderly with significant comorbidities or are unwilling to undergo a life-altering procedure,” Colin PN Dinney, MD, chairman of the Department of Urology, Division of Surgery, at The University of Texas MD Anderson Cancer Center in Houston, and a lead investigator of the phase 3 study, stated in a press release.1 “Intravesical gene therapy represents an important innovative treatment option for these patients. In this follow-up analysis of the phase 3 study, we demonstrated a sustained response to [nadofaragene firadenovec] treatment over three years, allowing more than half of the patients in the study to remain cystectomy free for at least 36 months.”

On December 16, 2022, the FDA approved nadofaragene firadenovec for the treatment of patients with high-risk BCG-unresponsive NMIBC with CIS with or without papillary tumors.4

A total of 157 patients with BCG-unresponsive NMIBC were enrolled into the two-cohort phase 3 trial; 107 comprised the CIS cohort and 50 comprised the papillary cohort.1,2 Additional eligibility criteria required life expectancy greater than 2 years, an ECOG performance status of 2 or less, and absence of concomitant upper tract urothelial carcinoma or urothelial carcinoma within the prostatic urethra.5 Patients with low-risk prostate cancer on active surveillance with prostate-specific antigen levels below 10 ng/dL, Gleason score 6, and cT1 were eligible dependent on the investigator’s discretion.

As part of the phase 3 trial, patients received 75 mL of nadofaragene firadenovec as an intravesical instillation (3 × 1011 viral particles/mL) once every 3 months for up to 12 months or until unacceptable toxicity or disease recurrence.1,2 Patients who were free from high-grade recurrence at 12 months were allowed to continue nadofaragene firadenovec every 3 months as part of an ongoing follow-up analysis. Overall, 12.1% (n = 13) and 20.0% (n = 10) of patients in the CIS and papillary disease cohorts, respectively, received nadofaragene firadenovec at 3 years.1

The primary end point was the rate of CR in patients with CIS with or without concomitant high-grade Ta or T1 papillary disease.5 Secondary end points included the durability of CR in patients with CIS, the rate of event-free survival (EFS) in the papillary disease cohort, durability of EFS in the papillary disease cohort, incidence and time to cystectomy, overall survival (OS), and durability of response in the extended follow-up period.

In the total population of 157 patients, the mean age at informed consent was 70.8 years (standard deviation [SD], 9.2).2 Most patients were male (82%) and had an ECOG performance status of 0 (89%). The mean time from initial diagnosis of bladder cancer was 28.6 months (SD, 32.6). Disease stage at the time of study entry included CIS only (52%), Ta (22%), Ta and CIS (13%), T1 (10%), or T1 and CIS (3%). Patients received 1 (4%), 2 (46%), or 3 or more (50%) previous courses of BCG courses.

Additional results demonstrated that the median duration of CR in both cohorts was 9.7 months (range, 9.2-24.0), with an estimated 34.2% (21.6%-47.1%) of patients predicted to experience durable CR for at least 3 years.1,2 Moreover, the estimated median duration of high-grade recurrence-free survival was 6.0 months (95% CI, 3.4-8.3) in the CIS cohort and 12.4 months (95% CI, 6.7-20.3) in the papillary disease cohort.

The estimated 3-year cystectomy-free survival rate was 53.8% (95% CI, 43.3%-63.1%) in the CIS cohort and 63.6% (95% CI, 48.0%-75.6%) in the papillary disease cohort. Additionally, the 3-year OS rate was 90.4% (95% CI, 82.3%-94.9%) and 90.7% (95% CI, 78.5%-96.7%) in the CIS and papillary disease cohorts, respectively.

Regarding safety, the regimen was well tolerated, and no new safety signals were observed during the 3-year follow-up period. During this time, 3 patients discontinued treatment because of non-serious adverse effects, including grade 3 bladder spasm and grade 2 instillation site discharge in the CIS cohort and grade 2 benign bladder neoplasm in the papillary disease cohort.

“[Nadofaragene firadenovec] is a novel therapy that has demonstrated its value as an effective and well-tolerated standard-of-care treatment for high-risk patients with NMIBC with CIS ± Ta/T1 who have BCG-unresponsive disease,” Pierre-Yves Berclaz, MD, PhD, executive vice president and chief science and medical officer, Ferring Pharmaceuticals, added in the press release.1 “This 3-year analysis provides further evidence for the durable efficacy and long-term safety of [nadofaragene firadenovec] in this on-label patient population, as well as additional data showing its therapeutic potential in a separate population of patients with NMIBC with papillary disease. We look forward to continuing patient follow up as we work to redefine the treatment of NMIBC.”


  1. Three-year follow-up data in BCG-unresponsive NMIBC show durable response to treatment with ADSTILADRIN (nadofaragene firadenovec-vncg) in two patient cohorts. News release. Ferring Pharmaceuticals. April 8, 2024. Accessed April 8, 2024.
  2. Boorjian SA, Narayan VM, Konety BR, et al. Efficacy of intravesical nadofaragene firadenovec-vncg for patients with Bacillus Calmette-Guérin–unresponsive non–muscle-invasive bladder cancer: 36-month follow-up from a phase 3 trial. Presented at: European Association of Urology; April 5-8, 2024; Paris, France. Abstract A0583.
  3. Boorjian SA, Alemozaffar M, Konety BR, et al. Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial. Lancet Oncol. 2021;22(1):107-117. doi:10.1016/S1470-2045(20)30540-4
  4. FDA D.I.S.C.O. Burst Edition: FDA approval of Adstiladrin (nadofaragene firadenovec-vncg) for patients with high-risk Bacillus Calmette-Guérin unresponsive non-muscle invasive bladder cancer with carcinoma in situ with or without papillary tumors. FDA. December 16, 2022. Accessed April 8, 2024.
  5. Adstiladrin (=Instiladrin) in patients with high grade, Bacillus Calmette-Guerin (GCG) unresponsive non-muscle invasive bladder cancer (NMIBC). Updated December 22, 2023. Accessed April 8, 2024.
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