BCG Shortage Warrants Treatment Shifts, New Treatment Strategies in Bladder Cancer

Bogdana Schmidt, MD, MPH

With the ongoing BCG shortage, de facto standards and novel treatment delivery strategies have helped stabilize and improve the bladder cancer space, particularly for patients with non–muscle invasive bladder cancer (NMIBC), according to Bogdana Schmidt, MD, MPH.

However, novel treatment approaches, including TAR-200 and UGN-102, have helped pave the way beyond BCG, especially for patients with BCG-refractory, high-risk NMIBC and intermediate-risk NMIBC, respectively.^1,2 In January 2025, a new drug application (NDA) for TAR-200 was submitted to the FDA to seek approval of the drug for the treatment of patients with BCG-unresponsive high-risk NMIBC and carcinoma in situ, with or without papillary tumors.¹ Additionally, in October 2024, the FDA accepted the NDA for UGN-102 for the treatment of low-grade intermediate-risk NMIBC, with a Prescription Drug User Fee Act target date of June 13, 2025.²

“Within the BCG shortage period, we've developed newer mechanisms of action and newer treatments,” Schmidt said in an interview with OncLive® during Bladder Cancer Awareness Month, observed in May. “These new treatments are exploding the field of NMIBC right now, most of which started for patients who have, by definition, BCG-refractory disease, because once a patient's disease doesn't respond to BCG, the standard of care is radical cystectomy.”

During the interview, Schmidt explained how BCG fits into the NMIBC treatment paradigm, emphasized the effect of the BCG shortage and subsequent navigation, and novel treatment strategies coming down the pike.

Schmidt is an associate professor in the Division of Urology at the University of Utah Huntsman Cancer Institute in Salt Lake City.

OncLive: How does BCG fit into the treatment paradigm for NMIBC?

Schmidt: Our treatments for NMIBC are focused on reducing those rates of progression and recurrence in that order, and the standard of care for high-risk NMIBC has been BCG for a long time. It's an immune modulatory intravesical treatment that is instilled in the bladder during clinic visits. It stimulates the patient's immune system to fight off the bladder cancer, and because it's an immune-mediated mechanism, we have a maintenance phase that's built into the program. After some time, the patient is restimulated with the BCG bacterium, and the immune system is supposed to mount a response to it effectively, the way it would towards a recurrent tumor. BCG is quite effective—it’s [approximately] 70% effective—but unfortunately, we've had a lot of BCG shortages and the inability to deliver BCG to patients for the amount of time that we know is necessary for best response.

How is the bladder cancer space navigating the BCG shortage, and what other treatment options are available?

It really is challenging. One of the things that a lot of people in the community have adopted as the de facto standard is gemcitabine/docetaxel. This is being prospectively evaluated against BCG in the BRIDGE trial [NCT05538663], which is accruing right now in the BCG-refractory space. It's going to read out probably in the next few years. Gemcitabine/docetaxel is often the de facto standard, partly because it's [more affordable], available, and there are no shortages. Most of us know how to use it, but it's very challenging to do in the community. Therefore, it's picked up in the academic settings, and not in the communities, because it has a very long chair time. Patients have to be in the clinic for at least 2 hours with this drug. That's difficult for patients and clinics for staffing reasons. We all have challenges with having our clinics fully staffed, especially after the COVID-19 pandemic.

People have also been using clinical trials. We're all grateful to all the industry's partners who have jumped into the space to try and create something new and exciting for our patients. And being able to put our patients on trial has helped quite a bit.

The FDA created a BCG unresponsive designation and allowed for single-arm clinical trials to open up the space. That's why we have all of these newer treatments being presented in abstract presentations. We've got 3 drugs FDA approved in this space and more to come in the high-risk NMIBC space. There's also an intermediate-risk NMIBC space, which is interesting, because these are patients that progress much less likely, but recur with their disease, and now treatments are attempting to reduce those recurrences, and potentially trying to reduce the number of health care visits, resections, and treatments that the patients may need for a disease that is less biologically dangerous from progression and metastatic potential, but can be a real burden on a patient's quality of life, finances, and personal time. All of these are very, very important factors. The NMIBC space has exploded in the last 5 to 10 years, and it's an exciting time.

What are some novel treatment delivery approaches and technological advances that are shifting the treatment paradigm?

The space is interesting because now we have new agents and delivery mechanisms for older agents. TAR-200 utilizes gemcitabine, which is an old familiar drug, but it delivers it in a very different way. UGN-102 uses mitomycin [Mitosol], another old familiar drug, but delivers it in this reverse hydrogel formulation, where it stays in the bladder and has a longer sustained delivery. We typically put it in, have the patient hold it for an hour, and have the agent come out. The new delivery mechanisms are fascinating, and that's only going to improve how we treat our patients.

Regarding technology and imaging, we're making progress in that as well, especially with using MRI for bladder cancer staging. However, that's not something that is as widely adopted yet in the bladder world as it has become in prostate cancer. It has transformed their prostate cancer spec, and the bladder space is still a little bit behind in that. It would be great for us to have separate markers for bladder as well, similar to prostate-specific membrane antigen [PSMA] PET for prostate cancer. People have evaluated PSMA for bladder cancer and saw some promise, but not enough to change the game. Therefore, that search is still ongoing for the right bladder agent for systemic disease.

Furthermore, other areas where technology is going to change how we [approach treatment strategies] are the use of artificial intelligence, [especially regarding pathology]. We already have a couple of companies in the space that, if a patient has markers based on pathology signatures, [it can help] predict response to certain therapeutics. For example, there's a company that can assess pathology slides and predict whether a patient’s tumor is more likely to respond to BCG, an immune-mediated pathway, or chemotherapeutic pathways, like gemcitabine/docetaxel. This is still really early work, but it's already out there and is commercially available. There are other companies in the space that are only going to get better, and that’s really great [to see].

References

1. New drug application initiated with U.S. FDA for TAR-200, the first and only intravesical drug releasing system for patients with BCG-unresponsive high-risk non-muscle-invasive bladder cancer. News release. Johnson & Johnson. January 15, 2025. Accessed May 13, 2025. https://www.investor.jnj.com/news/news-details/2025/New-Drug-Application-initiated-with-U.S.-FDA-for-TAR-200-the-first-and-only-intravesical-drug-releasing-system-for-patients-with-BCG-unresponsive-high-risk-non-muscle-invasive-bladder-cancer/default.aspx
2. UroGen announces FDA acceptance of its new drug application for UGN-102. News release. UroGen. October 15, 2024. Accessed May 13, 2025. https://investors.urogen.com/news-releases/news-release-details/urogen-announces-fda-acceptance-its-new-drug-application-ugn-102