Inlexzo: A New Option For Bladder Cancer Patients When BCG Immunotherapy Stops Working

The approval, granted under Priority Review and supported by a Breakthrough Therapy Designation, is a much-needed milestone. It’s the first intravesical drug-releasing device, or device that releases medicine directly into the bladder, ever approved for bladder cancer.

The treatment involves several steps:

• A device smaller than a quarter, shaped like a pretzel, is placed inside the bladder.
• It slowly releases chemotherapy directly into the tumor environment, continuously, over three weeks.
• It is then removed and replaced at the next visit.

The whole procedure can be done during an office visit.

“What makes Inlexzo distinct is that it’s not simply delivering intravesical gemcitabine in the way we would traditionally think about it,” Dr. David Aggen, a genitourinary medical oncologist at Memorial Sloan Kettering Cancer Center in New York City, tells SurvivorNet.

“It’s an intravesical delivery system where a device is inserted into the bladder, it remains in place for about three weeks, and then it provides a sustained local release of gemcitabine, which is very different from standard intravesical gemcitabine, where the drug is instilled as a liquid and may have a short dwell time.”

The Promise of Inlexzo

To understand why this approval matters, it helps to know what patients are up against before they ever get to Inlexzo.

Non-muscle invasive bladder cancer is the most common form of bladder cancer. The standard first-line treatment is BCG (bacillus Calmette-Guérin), an immunotherapy drug that’s been a cornerstone of bladder cancer care for years. Delivered directly into the bladder, BCG works for many patients. But for a meaningful subset, the disease either never responds or comes back within months.

When that happens, the medical term is “BCG-unresponsive,” and the traditional recommendation has been radical cystectomy, or the surgical removal of the bladder.

A cystectomy is a major surgery, and many patients would prefer to avoid the procedure and long-lasting changes that come with it. This makes Inlexzo an incredibly welcome alternative.

Inlexzo is not the first drug to enter this space. Pembrolizumab (Keytruda), nadofaragene firadenovec (Adstiladrin), and nogapendekin alfa inbakicept (Anktiva, used with BCG) have all received FDA approval for BCG-unresponsive disease in recent years. But as Dr. Aggen explains, it’s the way Inlexzo is delivered in a sustained, localized way that matters.

“The value of TAR-200 is that it delivers gemcitabine slowly over the course of weeks,” Dr. Aggen says.

Gemcitabine, the chemotherapy agent inside the device has been used in bladder cancer for years. But its effect when administered conventionally has always been limited by the fact that it only stays in contact with bladder tissue for a short window (sometimes 30 minutes to an hour) before being excreted in urine. Inlexzo sidesteps that problem.

“We think the sustained exposure of gemcitabine may result in more drug exposure ultimately to the cancer and that you may have better outcomes. That’s the particular advantage,” Dr. Aggen adds.

In clinical trials, about 8 out of 10 patients had no detectable cancer at some point during treatment, suggesting a strong level of activity in this difficult-to-treat population.

How The Device Works

An “intravesical device,” may sound intimidating, but Dr. Aggen notes that the installation and removal is a realitively simple in-office procedure.

“The device is inserted as a linear device,” he says. “Inside the bladder, the device is about the size of a quarter. It folds up almost in a pretzel-like shape, and then it’s retrieved at every three-week installation to introduce a new device.”

Patients don’t need to hold their urine or follow any special preparation before the procedure beyond arriving with a non-empty bladder. After insertion, they’re advised to stay well-hydrated (about six to seven cups of fluid per day) and to urinate normally. There’s no need to restrict activity or alter daily routines.

The dosing schedule runs over two years in two phases:

• In the first six months, patients receive the device every three weeks (eight total doses).
• After that, dosing shifts to once every 12 weeks for up to 18 more months (six additional doses).

Despite the enthusiasm around Inlexzo’s efficacy, Dr. Aggen emphasizes that this treatment is not for everyone with BCG-unresponsive disease, and thoughtful patient selection is essential.

“Inlexzo is a favorable option for patients who have BCG-unresponsive disease,” he says. “I think that patients need to have a component of carcinoma in situ. Patients that have pure T1 disease that’s refractory to BCG [still progresses on BCG] are a much higher risk group, and perhaps those are patients who should be sent to their urologist for a discussion of an early cystectomy.”

The treatment schedule can also be taxing on patients, he adds.

“It does require device installation every three weeks for a set period of time, and you need a patient who’s willing and agreeable to go through those procedures,” Dr. Aggen adds. “It’s very distinct from BCG, which is given weekly for six weeks, and the frequency of administration may be cumbersome for certain patients.”

His advice to patients is to work closely with their urologists and care teams.

“With any intravesical therapy, it’s really important to be on the same page with your urologist about what the surveillance plan is so you don’t miss a cancer coming back more aggressively,” he adds.

Overall, Inlexzo represents a promising new kind of treatment, one that delivers chemotherapy directly to the bladder over time and may help some patients avoid or delay major surgery, but it is not the right choice for everyone.

Questions To Ask Your Doctor

• If my cancer becomes BCG-unresponsive, is Inlexzo an option for me?
• What are the risks v. benefits of choosing Inlexzo instead of getting surgery?
• How will I be monitored on Inlexzo?
• What potential side effects should I be on the lookout for?

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