Early Experience Program Doses First Patient With Intravesical Gene Therapy at Urology Practice

In December 2022, the FDA approved nadofaragene firadenovec-vncg (Adstiladrin; Ferring Pharmaceuticals) for adult patients with high-risk BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC) with carcinoma in situ with or without papillary tumors. It is a nonreplicating adenovirus vector–based therapy containing a gene-encoding interferon a-2b protein that is administered by catheter directly into the bladder once every 3 months. The vector enters the cells of the bladder wall, releasing the active gene and causing the bladder cell walls to secrete high quantities of interferon a-2b protein, which is a naturally occurring protein the body uses to fight cancer. This approach essentially turns the bladder cell walls into interferon microfactories, enhancing the body’s own natural defenses against the cancer.

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Starting in September 2023, Ferring Pharmaceuticals made this intravesical gene therapy commercially available through its Early Experience Program. The program offers the therapy to a mix of community clinical sites and clinical trial sites that participated in the phase 3 study. A patient under the care of the Wichita Urology Group in Kansas was the first treated under this program.

The Wichita Urology Group is a clinic that sees many high-risk adult patients with NMIBC who may be eligible for intravesical gene therapy. For this reason, Philippe Nabbout, MD, a urologist with the Wichita Urology Group, explained that his practice was particularly excited to gain access to this novel treatment.

However, given that gene therapy is complex to manufacture and scaling up production takes time, Nabbout explained that he recognized that the treatment might be difficult to obtain following its approval. The Early Experience Program provided an avenue for several eligible candidates in the clinic to receive the treatment. According to Nabbout, patients with BCG-unresponsive NMIBC have few treatment options aside from cystectomy, which is the partial or complete removal of the bladder.

“Many of the patients in our clinic are too sick to undergo this procedure, so being part of this program allowed us to offer our patients a much-needed alternative treatment option,” Nabbout said. “Some of our patients also stay informed about the latest medicines and, after hearing about the FDA approval, we received questions about this intravesical gene therapy.” Nabbout explained that the first dosed patient in the program was a 78-year-old man, and he was unresponsive to BCG therapy and was not well enough for cystectomy. “You can imagine how happy we all were to offer him a new treatment option,” Nabbout said.

Nabbout explained that, before starting treatment instillation, he conducted an overall evaluation of the patient to ensure there were no infections or other issues that might impact treatment. For example, bladder spasms during the procedure can affect retention of the liquid preparation in the bladder, causing significant challenges. Urologists who participated in the phase 3 clinical trials recommended administering antispasmodics during instillation as a way to reduce this risk, according to Nabbout.

“For the first patient treated in our clinic, we scheduled the procedure for the afternoon,” he said. “The intravesical gene therapy is stored frozen, at less than or equal to negative 60 °C [ ≤ –76 °F], and an afternoon appointment allows us to confirm with the patient in the morning and then thaw the product for [approximately] 5 to 6 hours prior.”

From the paperwork and ordering to storage, thawing, and instillation, the entire process went smoothly, Nabbout said. The administration of the intravesical gene therapy was similar to BCG instillation, which his practice has significant experience administering.

“Our patient also had been treated with BCG, so from his perspective, the instillation with intravesical gene therapy felt familiar and comfortable,” Nabbout said. “He showed little discomfort with the catheter and in retaining the liquid medication in his bladder.”

Nabbout noted that nadofaragene firadenovec-vncg is a particularly beneficial treatment for patients who are BCG unresponsive and are older and/or frail and cannot undergo cystectomy. For these patients, the intravesical gene therapy option is worthwhile to consider, according to Nabbout.

“For too many years, there has been very few advancements made in the treatment of high-risk BCG-unresponsive NMIBC,” Nabbout said. “With intravesical gene therapy, we now have a welcomed treatment option.”

Editor’s Note: This article features Phillipe Nabbout, MD, a urologist with The Wichita Urology, Group who dosed the first patient with nadofaragene firadenovec-vncg (Adstiladrin; Ferring Pharmaceuticals) in Ferring’s Early Experience Program. Since it was written, Ferring announced on January 16, 2024, that nadofaragene firadenovec-vncg is fully available across the US for health care providers to prescribe for their adult patients with high-risk BCG-unresponsive NMIBC with carcinoma in situ with or without papillary tumors. For more information, see the news release found here.