Nadofaragen Firadenovec is effective with a beneficial dosage plan in the real world for BCG-not-responious NMIBC

The favorable dosage plan of Nadofaragene Firadenovec-VNCG (Adstiladrin) makes it a suitable option for patients with BCG-not-response non-muscle-invasive bladder cancer (NMIBC) Moyer, BS.

“The most important, nadofaragene Firadenovec, and this can apply to many intravesical therapies. [is that] Bladder pasms and subsequent loss of the drug are a real problem, ”said Tyson in an interview with Oncline^®. “This is because it is $ 60,000 per dose or [in that range]; It is one thing when you let Gemcitabine expire with 26 US dollars per dose, it is a completely different fish kettle to violate Nadofaragen Firadenovec for $ 60,000 per dose. “

Data from a real study carried out by Moyer, Tyson and colleagues at the locations of the Mayo Clinic showed that patients who received intravesical therapy (n = 43), with a medium follow-up of 8.2 months, achieved a cystectomical survival rate of 95% and all patients in the data waste were alive.¹

“[In terms of] The real findings, although our numbers appear to be favorable, is too early to say that Nadofargenevec in the real world is no worse than in clinical studies, which is promising, ”we added in the interview.

In the interview, detailed results from the real study and considerations between Nadofaraleneovec and Nogapendekin Alfa Inbakicept-PMLN (Antiva), both of which are approved for patients with BCG-Unresponsive NMIBC.^2.3 Moyer is a graduate at the Mayo clinic in Scottsdale, Arizona, and Tyson is a urological oncologist and extraordinary professor of urology at the Mayo Clinic Alix School of Medicine in Arizona.

Oncline: What was the reasons for the introduction of the real study and how was it carried out?

Moy: Since Nadofaragene Firadenovec received the FDA approval in December 2022 [have not been] All published real data. On the symposium of 2025 ASCO Genitourary Cancers, we presented the first real data for patients with FDA-defined BCG-not-response NMIBC. We did this through a retrospective review of all patients who were treated at 3 Mayo clinic offices in Arizona, Minnesota and Florida between the first dose outside of a clinical study in November 2023 and December 2024 when we earned our last data for this project.

What were the most important findings and security results from the study?

Moy: We had 46 patients who were treated, and 3 of these 46 patients had 3 pending cystoscopy after the treatment. [Therefore]We had 43 effectiveness patients and 43 patients, 24, had a carcinoma in situ [CIS] with or without papillary illness. At the first evaluation [which was] For 3 months, 79% of patients with CIS had a complete reaction [CR]And that was durable [with high-grade recurrence-free survival (RFS) rates of] 74% after 6 months and 60% after 9 months. In the papillary cohort of 19 patients, the 3-month RFS rate was 68%, which was durable [with high-grade RFS rates of] 57% after 6 months and 40% after 9 months. The restriction was that the 6- and 9 months [rates] were chaplain Meier estimates, while the 3-month return rates were simple percentages. The total survival rate was 100% [as well].

We had 46 patients for whom we were able to rate security, and we mainly saw inferior transient and local side effects [AEs] that were managed in the clinic during treatment. We only saw 9% of the patients [experienced] AES of class 3, which included fatigue, fever and dizziness. We mostly saw [grade 1 or 2] Bladder cramps, a certain leak of the medication and urgency of micturition, [and this was] In accordance with the findings of phase 3.

What is for doctors because Nadofaragene Firadenovec is a newer drug, is most important about their administration/use?

Tyson: Perhaps one of the most important parts of this entire equation is to ensure [medication]. We went through a number of iterations in our practice and landed on Rectaldiazepam [Valium]. We give 10 mg of rectal diazepam suppository about 15 minutes before the instillation and we have data that will hopefully be released in a few months that show [it] essentially eliminated the loss of the medication. It didn't quite remove it, but [there was a] Drastic reduction in both bladder cramps and in particular involuntary contraction and loss of medication around the catheter.

Are there in particular patients who would be particularly good candidates for this medication?

Tyson: The indication of the drug is [for those with] BCG-not reacting NMIBC with CIS, so that this are the most suitable candidates who have rejected a radical cystectomy or are not justified and have diseases that do not react to conventional intravesical BCG treatments. We used the drug-off label in patients with only one BCG-not reacting papillary disease, which is so high-quality TA [and] There may even have been a few patients with T1. In my practice, I hesitate to use one of these intravesical therapies for [patients with] BCG-not reacting T1 disease. These are not ideal candidates, and these patients should be treated with cystectomy, but for someone who has a small amount of highly grade papillary-ta disease, it can be reasonable to consider this [nadofaragene firadenovec] In contrast to cystectomy.

The one -time 90 -day administration is ideal for patients who travel long distances for their care, and this could be true in an academic center or a rural group practice. There are many patients who have to cover long distances, and this would be a reasonable therapy that can be tried in particular in these patients.

Moy: The schedule for the forgiveness of treatment [is key]. We don't have the power to make in front of the Baseline characteristics [testing] To see which good predictors are for, who will do this well [therapy]But the forgiving treatment plan is a factor that you have to take into account.

Are there patients in which you wouldn't use nadofaragene Firadenovec?

Tyson: I generally do not use it in patients with very risky NMIBC who need a radical cystectomy [such as patients with] High quality T1 [disease] With simultaneous CIS, lymphovascular invasion, [and] Maybe Histology variant -[those] Patients must have a radical cystectomy. I generally do not use it in patients with a defective bladder – capacity, poor compliance -[as those are] Patients that I suspect emphasize the medication around the catheter or who may have a deteriorated bladder function due to additional intravesical therapy. I also tend to bring these patients towards cystectomy, and I have not used them in patients who have no strictly defined BCG-not-respons. We follow that exactly. If you are exposed, I generally put these patients in a clinical study or more BCG.

For patients who are not or do not respond for BCG or not, the NCCN guidelines are Nadofaragene Firadenovec and Nogapendekin Alfa Inbakicept Options for the same patient population and Pembrolizumab are also available for selected patients. How would you choose between the 3 drugs?

Tyson: This is not a softball question; It's a difficult question. I think the days of Pembrolizumab [Keytruda] Monotherapy ends. If we had no other option and the patients did not want cystectomy or further intravesical therapy, Pembrolizumab Monotherapy was a reasonable option, but now we have intravesian therapies [with] Nadofaragen Firadenovec and Nogapendekin Alfa Inbakicept, which have just as well showed in clinical studies, possibly even somewhat better effectiveness and certainly better tolerance. With the 2 intravesical active ingredients we do not see any autoimmune-mediated systemic AES, so I believe that the risk-benefit ratio is generally promoted to the 2 intravesical therapies.

How to choose between these two medication is also a very difficult task. On the one hand, Nadofaragene Firadenovec is given as monotherapy every 90 days. On the other hand, Nogapendekin Alfa Inbakicept in combination with BCG is administered in classic induction and maintenance paradigm. If your practice is not on BCG, you will probably not use Nogapendekin Alfa Inbakicept, but when I said that Nogapendekin Alfa Inbakicept, I mentioned the leader in the clubhouse. It encountered the finish line with the highest CR rate a year in an FDA [studied] Population. There are advantages and disadvantages of administration and logistics, and [the data supporting the FDA approvals noted a 51% CR rate for nadofaragene firadenovec and 62% for nogapendekin alfa inbakicept]There may therefore be questions about comparative effectiveness.

I don't say that [one agent is] Better, we have to do science to meet this determination, but I could see how patients look at it and say: “I would rather have Nogapendekin Alfa Inbakicept.” Or I could also see how patients look at Nadofargee Firadenovec and say: “I would rather have that”. In my current practice I can prescribe both – I have just received the ability to prescribe Nogapendekin Alfa Inbakicept recently. I have a conversation with the patient and I explain the data for you and the risk/benefit relationships what it takes to do each of these therapies and I let them choose.

How do these findings of the real study help with your selection between the medicinal products?

Tyson: There are some cases, and in most cases it is correct in which the real data does not measure the clinical experimental data, and this is because the people we insert into clinical trials strongly checked, through a litany of the inclusion and exclusion criteria and simply do not reflect the average patients that we see in the clinic. The idea behind this study was how these medicines work for the average patient who is seen in the clinic. Although there is a big difference between the 79% 3-month CR rate in our real study and the [53]% [rate] In the phase -3 study observed, I hesitate to say that it is better. Our data do not show that Nadofaragen Firadenovec is more effective than we think it doesn't seem to be worse, and that is very encouraging to see in a real study.

References

1. Moyer J, Durant A, Nguyen M, et al. Real-world results of Nadofaragene Firadenovec in BCG-not reacting non-muscle-invasive bladder cancer. J Clin Oncol. 2025; 43 (Suppl 5): 716. DOI: 10.1200/JCO.2025.43.5_Suppl.716
2. FDA Disco Burst Edition: FDA approval of Adstiladrin (Nadofaragene Firadovec-VNCG) For patients with high risk bacillus calmette-guérin not reacting non-muscle-invasive bladder cancer with carcinoma in situ with or without papillary tumors. FDA. January 20, 2023. Access on March 10, 2025. to%20december 2016 %% 2C%202022%2C%20dhe, with%20%20 without%20 papillary%20tumors
3. The FDA approves Nogapendekin Alfa Inbakicept-PMLN for BCG-not reactionable non-muscular invasive bladder cancer. FDA. April 22, 2024. Access on March 10, 2025.