Dr. Narayan discusses 5-year data on nadofaragene firadenovec in NMIBC

In this video, Vikram M. Narayan, MD, offers insight on findings from the study, “Efficacy of nadofaragene firadenovec-vncg for patients with Bacillus Calmette-Guérin-unresponsive non-muscle-invasive bladder cancer: final results from a phase 3 trial,” which he presented at the 2024 American Urological Association Annual Meeting in San Antonio, Texas. Narayan is an assistant professor of urology at the Emory University School of Medicine in Atlanta, Georgia.

Video Transcript:

Could you describe the background for this study?

As you're probably aware, nadofaragene firdenovec or Adstiladrin was approved by the FDA in December 2022. There was a pivotal phase 3 SUO CTC trial. The PI of that was Steve Boorjian. It was performed in 33 sites across the United States, and it led to the FDA approval. That was a 12-month follow-up data. What we presented at the AUA was the 5-year follow-up. Essentially, we looked at safety and efficacy out to 5 years of follow-up and were excited to present those results.

What were the key findings presented at AUA?

Well, there are a few key takeaways. One was that, importantly, this is a first-in-class gene therapy drug that's intravesical for non–muscle-invasive bladder cancer, and there were no new safety signals that were seen out to 5 years of follow-up, which is super important. The other was that we found that about half of the patients in the CIS cohort and two-thirds of those in the Ta/T1 or papillary cohort had bladder preservation, meaning they were able to avoid cystectomy. As you know, that's a very important outcome for patients. Very few patients discontinued the drug due to side effects, and there were no study drug-related grade 4 or 5 adverse events.

In terms of complete response and durability of complete response, 14 out of 55 patients in the CIS cohort had ongoing response at the time of their last disease assessment. And 17 out of 35 patients in the papillary cohort, the high-grade Ta/T1, cohort, had ongoing response at their last assessment. In terms of how that shakes out with respect to Kaplan Meier probabilities, at 57 months in the CIS cohort, the probability of remaining high-grade recurrence-free was around 13%, with a median duration of around 9.7 months. In the papillary or high-grade Ta/T1 cohort, the probability of remaining high-grade recurrence-free at 57 months was around 32%. So, there's still more work to be done. This is a drug that we're excited about having available for our patients. But clearly, we would always like to see better long-term durability.

I will call out though, that if you look at 1 year durability out from what we initially reported, it was around 25% or so in terms of how many patients had durability at 1 year. So, out to 5 years, that number dropped by only about 50%, which, that's pretty good for this disease state. It's, again, like I said, not perfect, but we're very happy to be able to provide this very long-term data. There are few other alternatives on the market with this long-term, high-quality data.

I think a couple things to point out as well are that this is a very regular rigorously run study. At the time the study was designed, there were very few other similar options available. So, we were very concerned about potentially the risk of progression and safety for patients to try alternative therapies. As a result, no patient received retreatment when they received nadofaragene on trial. The only patients who received retreatment were those who had a complete response. So, if you had a high-grade recurrence, you were taken off trial or taken to cystectomy, depending on the discretion of the treating physician. That's important to highlight because, obviously, there's a number of comparisons being made with other drugs that have since emerged. I think it's great to see all these new options for our patients, and these comparisons are inevitable, but one thing to just keep in mind is the fact that many of the other treatments that have been evaluated, the trials for those did allow retreatment, but this trial did not allow retreatment. I think that's an important call out. Another thing is every patient was required to undergo mandatory 12-month biopsy. That's also significant because we didn't rely just on clinical factors for assessing recurrence. We did during the 3-, 6-, 9-month time points, but at 12 months, regardless of whether the investigator determined the patient to have complete response or not, they were required to take the patient for a mapping, biopsy and cytology. That's significant because it allows for the gold standard truth of whether that patient actually had a complete response or not. That adds an additional layer of, I think, rigor to the study results.

This transcription has been edited for clarity.