Behind the FDA approval of Inlexzo in NMIBC, with Sia Daneshmand, MD

The FDA’s recent approval of the gemcitabine intravesical system, Inlexzo (formerly TAR-200)¹, represents a significant advancement in the treatment of patients with BCG-unresponsive non–muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), with or without papillary tumors. By providing extended local delivery of a cancer medication into the bladder—the first system of its kind to do so—Inlexzo overcomes some of the tolerability challenges associated with traditional therapies.

Notably, Inlexzo has also demonstrated significant efficacy, achieving a complete response (CR) rate of 82% (95% CI, 72 to 90) in cohort 2 of the phase 2b SunRISe-1 trial (NCT04640623). SunRISe-1 supported approval of Inlexzo in patients with BCG-unresponsive NMIBC with CIS with or without papillary tumors who are ineligible for, or elected not to undergo, radical cystectomy. This high response rate also showed strong durability, and 51% of these patients maintained a CR for at least 1 year.¹

In a recent interview with Urology Times®, SunRISe-1 principal investigator Siamak Daneshmand, MD, shared his thoughts on the implications of this approval for clinical practice. Daneshmand is a professor of urology and oncology as well as the director of urological oncology at the University of Southern California Norris Comprehensive Cancer Center in Los Angeles, California.

Urology Times: Could you explain the mechanism of action for Inlexzo?

Daneshmand: Inlexzo is an intravesical drug-releasing system that provides extended release of gemcitabine into the bladder. That's important, because the medicine has time to penetrate the deeper layers of the bladder. The traditional treatments are in aqueous form, where they're placed in the bladder for 1 hour at a time. That's not enough time for the medication to get into the deeper layers and cover the whole bladder. That was the whole premise behind this system—if we had it in there for longer, perhaps the gemcitabine can work better, and that's exactly what we're seeing now with the trial.

Urology Times: As a urologist treating patients with bladder cancer, what excites you most about Inlexzo as a new option for non–muscle invasive bladder cancer?

Daneshmand: When it comes to BCG-unresponsive disease, we have limited treatment options. The traditional treatment option has been radical cystectomy, removal of the bladder, and urinary diversion, which carries a high cure rate, but it’s a major change in the patient's lifestyle, quality of life, and carries with it a significant morbidity and mortality in elderly patients. We’ve also had intravesical treatments of various agents, [like] chemotherapy, which has had limited success, especially when it comes to durability.

We'd like to have treatment options that work well for these patients. We welcome the addition of treatments that are efficacious and have a higher duration of response. That's what's most exciting for me, is to have yet another way to treat patients who are unresponsive to BCG.

Urology Times: As you know, the SunRISe-1 trial reported an 82% complete response rate and durable responses beyond 12 months in over 50% of patients. How do you interpret the clinical significance of these results for long-term disease control?

Daneshmand: That's a very high complete response rate, one of the highest we've seen in this space, so it's very exciting to know that we have an efficacious treatment. The other equally important part is the duration of response. Many drugs work initially, and then there's a degradation of response as time passes. However, we're seeing more than half the patients are responding at 1 year. This is something that's working long-term, which we're very excited about.

Obviously, it's an ongoing trial, and we are continuing to follow the patients long-term, but we already have many patients, including some of mine, who are out more than 2 years and are disease-free and have their bladders intact. This concept of having an intact bladder and long-term disease-free survival is a key point in this trial.

Urology Times: How do you envision Inlexzo fitting into your treatment algorithm? Which patients are the most appropriate candidates for this therapy?

Daneshmand: Fortunately, there are very few contraindications to placement of the drug releasing system and using the medication. Gemcitabine is a medication with which we're all very familiar. We've been using it in its aqueous form for years, and we still do in combination with docetaxel. We're very used to the medication itself, but the system is new. Again, there are very few contraindications to placing this system in the patient. Just like the trial inclusion criteria, anyone who's unresponsive to BCG who has CIS with or without papillary tumors is eligible for the treatment.

Urology Times: What are some of the biggest practical considerations for administering Inlexzo in clinic?

Daneshmand: I think one of the unique features of this treatment is that it's off the shelf, if you will. That means that it's readily available. There's no thawing process. There's no preparation that's required. There's no special handling. It comes in a box and everything you need is there.

We place Inlexzo into the bladder using a co-packaged urinary catheter and stylet to insert it into the bladder. Urologists are used to catheterizing patients for intravesical treatment. Inlexzo uncoils as it goes inside, and it recoils as it enters the bladder. It has a nitinol wire inside that allows it to retain its shape while inside the bladder. The most significant part of this is that it's a quick process. It's something we're all very used to as urologists. Inlexzo is placed in an outpatient setting in a few minutes, without the need for general anesthesia or further monitoring immediately post-insertion within the clinician's office. Advanced practice providers, such as nurse practitioners and physician assistants, can also place Inlexzo.

In terms of removal, this is again something we're very much used to as urologists; it's like removing a stent. We have a cystoscope and a grasper that can grasp one end of this drug releasing system and pull it out quite easily. The significance is less time for patients in terms of insertion and removal, and for the practitioner, it's also less burdensome than treatments that may take a longer time to instill and remove.

Urology Times: What is the safety profile for Inlexzo? Based on the data, how well is this treatment tolerated?

Daneshmand: That's one of the questions I get all the time: What are the [adverse] effects of this? After all, this is a drug-releasing system that's placed in the bladder that you're carrying for 3 weeks at a time. The patients in the study were asked about [adverse] effects at each visit, and these were very carefully annotated in the manuscript.

In the SunRISe-1 clinical study, the majority of adverse events were mild to moderate. These included adverse reactions that we're accustomed to with any treatment for bladder cancer, such as urinary frequency, urinary tract infection, dysuria, and micturition urgency. Permanent discontinuation of Inlexzo due to an adverse reaction occurred in 7% of patients. That's been my experience with the other trials and with the system as well, that the vast majority of patients tolerate it well.

Another point is that in my experience, it's not so much the drug-releasing system itself as it is the drug that causes some of these [adverse events]. Gemcitabine can be somewhat acidic, so we do have medications that can ameliorate the [adverse] effects of the medication. For dysuria, frequency, and urgency, we use anticholinergics or β3 agonists to control that. Occasionally, and because of the acidic nature of the gemcitabine, we use sodium bicarbonate or alkalizing the urine to help with that. Again, there were very few discontinuations, and we want to stress that as well.

Urology Times: How might Inlexzo change the treatment landscape for patients who are hoping to preserve their bladder and avoid surgery?

Daneshmand: For decades, we have been very limited in the number of medications and treatments available for patients, specifically for non–muscle invasive bladder cancer. Obviously, we've always had radical cystectomy as an option for patients, but for patients who don't have muscle-invasive disease, having alternate treatment options is [crucial].

There are a number of other drugs being developed in this space, and we're lucky to have a few that have already had FDA approval and others in development. But even with the approval of alternate drugs and treatments in this space, we still need additional medications, because, as you can see, in 1 year and 2 years, many of the patients are still having recurrences, and we need to move on to other therapies. These are patients who often have multiple treatments in their bladder and are moving to second- and third-line therapies. This concept of having additional treatments and sequencing these medications and treatments is of utmost importance for the patients who are very motivated to keep their bladders and their disease away. I think the fact that [Inlexzo] has very high response rates and is very well tolerated [means that this is] something that we can go to easily in terms of the next line of treatment for the patients who haven't responded to previous treatments.

One of the other issues is that, in the near future, we'll be doing more studies to see how patients will respond after other treatments in the bladder. This is just the very beginning of an exciting time for us clinicians and researchers to understand where else we can use this drug-releasing system.

The most important [point] for patients is to know that they have yet another treatment option available to them prior to going to radical cystectomy as the last resort. There are many patients who are not candidates for intravesical treatments because they can't tolerate the volume of the solutions that are put in the bladder. With traditional treatment, we're putting 7500 ccs of the solutions [such as] BCG or chemotherapy inside the bladder and asking them to hold it for at least an hour. Many patients are unable to do that. Because this is a drug-releasing system that's placed in the bladder, we don't need to ask patients to hold on to it. This is a small system that is placed in the bladder and sort of floats around. The other important point is [its size]. It's very small; it's the size of 2 quarters placed together side by side. And again, it is very well tolerated.

I think that most important thing is that this another highly effective treatment option available for patients [with BCG-unresponsive NMIBC].

REFERENCES

1. U.S. FDA approval of INLEXZO (gemcitabine intravesical system) set to transform how certain bladder cancers are treated. News release. Johnson & Johnson. September 9, 2025. Accessed September 10, 2025. https://www.jnj.com/media-center/press-releases/u-s-fda-approval-of-inlexzo-gemcitabine-intravesical-system-set-to-transform-how-certain-bladder-cancers-are-treated