Early Experience Using Intravesical Gene Therapy for NMIBC: Perspectives from Urinary Oncologists

Every year in the United States, there are more than 82,000 new diagnosed cases of bladder cancer and 16,700 associated deaths.¹ Along with common carcinogens such as smoking and environmental exposure, age and gender are 2 important risk factors for bladder cancer. Men are affected 3 times more often than women, with bladder cancer being the fourth most common cancer among men.¹ Nine out of 10 bladder cancer patients are over age 55 with an average age of 73 years at diagnosis.¹

Most bladder cancers are urothelial carcinoma, a malignancy of the urothelial cells lining the bladder and the majority of the genitourinary tract.² In approximately 75% of cases, the cancer is still contained within the inner walls of the bladder. This type is known as non-muscle-invasive bladder cancer (NMIBC). For nearly half a century, the standard of care for NMIBC patients has been Bacillus Calmette-Guerin (BCG) or intravesical chemotherapy. Not all patients respond to this treatment, particularly after recurrence. In fact, more than 50% of high-risk patients experience recurrence the first year of BCG therapy,³ and up to half become unresponsive to BCG therapy.⁴ For BCG unresponsive NMIBC, the standard approach has been radical cystectomy—the partial or complete removal of the bladder.

For more than 30 years, there has been little treatment advancement for NMIBC patients. Fortunately, a new development in the treatment of NMIBC has been approved by the FDA and is now available.

In 2022, the FDA approved Ferring Pharmaceuticals’ nadofaragene firadenovec (Adstiladrin), the first and only intravesical gene therapy for the treatment of patients with BCG-unresponsive NMIBC. It is a non-replicating adenovirus vector-based therapy containing the gene interferon (IFN) alfa-2b, with antitumor activity that represents a novel addition to the treatment options available for this difficult-to-treat patient population.

Given the limitations with current treatment options for BCG-unresponsive NMIBC patients, this intravesical gene therapy represents a promising treatment option for patients, one that the uro-oncology community has been eagerly awaiting.

Treatment is administered every 3 months directly into the bladder. Administration is non-invasive, not labor intensive, and doesn’t require an induction period. It can be completed in the urologist’s office or outpatient setting, locations that patients are already comfortable and familiar with.

As a trial site for the phase 3 clinical research, our team at Banner MD Anderson Cancer Center found intravesical gene therapy to be an effective and well-tolerated treatment option with a manageable safety profile. Treatment has demonstrated a durable response, especially for patients who are unfit for or unwilling to undergo cystectomy. Importantly, the patients we treated in the clinical trial were satisfied with therapy as in many cases, we were able to preserve the bladder.

There are inherent challenges in manufacturing a gene therapy, including the complexities of encapsulating the gene and preparing the viral vector, as well as scaling production from clinical trial to commercial. Recognizing those challenges, Ferring first made nadofaragene firadenovec available through an Early Experience Program to ensure patients with the highest need received access while production scaled up. This included a mix of phase 3 trial sites and select clinics with high-risk NMIBC patients.

Our urinary oncology team at Banner was among the first clinical trial sites to treat patients as part of this Early Experience Program. This allowed us to provide continuing treatment for patients in our clinic who took part in the clinical program as well as to treat new patients referred to us by urology practices in our community. We were pleased to be a part of this program because many difficult-to-treat cases were referred to us at Banner MD Anderson Cancer Center due to our extensive experience with these patients. This gene therapy represents a good alternative option for patients who are elderly, have co-morbidities, and are too sick to undergo surgery or don’t want to undergo such an invasive procedure.

Further, what really excites us—and surely other urologists—is that Ferring recently announced that it has increased product supply ahead of schedule and can now provide this gene therapy to appropriate NMIBC patients.

About the Authors

Chinedu Mmeje, MD, FACS, is a urinary oncologist with Banner Gateway Medical Center in Gilbert, Arizona.

Joseph Mashni, Jr., MD, is a urinary oncologist with Banner Gateway Medical Center in Gilbert, Arizona. He also was an investigator on the Phase 2 and 3 studies in the clinical trial program for nadofaragene firadenovec-vncg.

We believe that access to new treatment options for patients with NMIBC remains critical. The development of intravesical gene therapy for NMIBC provides the first promising change in nearly a half-century entrenched treatment paradigm, representing a significant advancement for patient care. Pharmacy professionals need to be kept informed of this latest treatment development for bladder cancer. Because pharmacists are often on the frontlines and answering questions about new treatment options and their availability, it is important that they know about this novel gene therapy and its supply and are well-versed in its background and significance for health care providers and bladder cancer patients.

2. What Is Bladder Cancer? National Cancer Institute. Updated February 16, 2023. Accessed February 27, 2024. https://www.cancer.gov/types/bladder

3. Hussain MH, Wood DP, Bajorin DF, et al. Bladder cancer: narrowing the gap between evidence and practice. J Clin Oncol. 2009;27(34):5680-5684. doi:10.1200/JCO.2009.23.6901

4. Kamat AM, Lerner SP, O’Donnell M, et al. Evidence-based assessment of current and emerging bladder-sparing therapies for non–muscle-invasive bladder cancer after Bacillus Calmette-Guerin therapy: a systematic review and meta-analysis. Eur Urol Onc. 2020;3(3):318-340. doi:10.1016/j.euo.2020.02.006