Dr. Narayan describes how nadofaragene firadenovec works in NMIBC

Commentary
Video

"Because it takes advantage of a viral vector and is delivered as a gene therapy product, what it can do is it can have sustained release of IFNα2b in the bladder," says Vikram M. Narayan, MD.

In this interview, Vikram M. Narayan, MD, discusses the background and key points addressed in the publication, “Mechanism of action of nadofaragene firadenovec-vncg,” for which he served as the lead author. Narayan is an assistant professor of urology at the Emory University School of Medicine in Atlanta, Georgia.

Video Transcript:

Could you discuss the background for this work?

Most of those of us who treat bladder cancer in the urologic community have been aware of the exciting FDA approval last year of nadofaragene firadenovec, also known as at Adstiladrin, for use in patients with BCG-unresponsive, non–muscle-invasive bladder cancer. The approval was for patients who have carcinoma in situ with or without papillary tumors. This is a space that has, unfortunately, historically had very few options. We have relied on BCG, as well as intravesical chemotherapy. Many patients, of course, go to radical cystectomy. With this drug's approval, one of the questions that has come up is, how does it work? Obviously, folks are like, "well, it's very difficult to pronounce," but what happens when a patient gets this drug? What's the mechanism of action? This is intended to help clarify that and provide some information for those who may be interested in that specific question.

What were the key points highlighted in the paper?

Nadofaragene is a gene therapy drug. It's actually the first in class intravesical gene therapy drug that has been approved for this space. The paper has an overview of the background of non–muscle-invasive bladder cancer and the scope of the problem, but then spends a good amount of time where we try and explain what happens and provide justification for the dosing schedule. One of the things that patients have really taken upon favorably with this drug is that it's dosed once every 3 months, as opposed to once weekly, like many other existing treatments. A question that may come up for folks is, "well, how does that work?" The way it does work is by delivering IFNα2b via an adenoviral vector that's given intravenously in the bladder. What it does is it turns the bladder cancer cells into a little bit of a factory to produce IFNα2b, and that then goes on to stimulate the body's immune system in a way that triggers things like anti-angiogenesis or apoptosis, cell death. Because it takes advantage of a viral vector and is delivered as a gene therapy product, what it can do is it can have sustained release of IFNα2b in the bladder for a longer period of time than you might get if you were to just instill the medication and let it sit in the bladder for a while.

This transcription has been edited for clarity.

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