First FDA-Approved Adenoviral Vector-Based Gene Therapy for Bladder Cancer

Receiving news of a cancer diagnosis is a devastating challenge to face for any patient and their loved ones. Even more so where there are few treatment options the individual can consider. In the case of adults with high-risk non-muscle invasive bladder cancer (NIMBC), immunotherapy drugs like Bacillus Calmette-Guérin (BCG) are a primary method of treatment for boosting the immune system’s capability to fight off cancerous cells. Yet, there are many with high-risk NIMBC who unfortunately fail to respond to BCG therapy, so where else can they turn?

Adstiladrin Becomes First-of-its-Kind Therapy for Bladder Cancer

As of December 16, 2022, Adstiladrin (nadofaragene firadenovec-vncg) from Ferring Pharmaceuticals became the first adenoviral vector-based gene therapy approved for NIMBC by the Food and Drug Administration (FDA). Merck’s pembrolizumab was already approved for this indication back in January 2020, but nadofaragene firadenovec is changing the game as the first recombinant adenovirus offered for bladder cancer patients. When administered, Adstiladrin enters cells to introduce a gene for interferon alpha 2b (IFNα2b) into their DNA but is unable to replicate in human cells. The resulting increase in IFNα2b expression by cancerous bladder cells results in inhibition of their excessive growth.

What is Non-Muscle Invasive Bladder Cancer (NIMBC)?

NIMBC is a type of superficial bladder cancer that grows within the inner lining but has not metastasized into the bladder’s muscle layer. Not only is it the sixth most common form of cancer in the United States, nearly 75% of all new cases of bladder cancer are classified as NIMBC. In the US alone, over 80,000 individuals were estimated to have been diagnosed in 2022. Adstiladrin was granted Priority Review, Breakthrough Therapy, and Fast Track designations by the FDA because its results presented a potential for advancing BCG-unresponsive NIMBC medical care.

Adstiladrin Shows Safe, Effective Clinical Trial Performance

Adstiladrin was found to be both safe and effective in prior phase I and phase II studies, allowing Study CS-003 (NCT02773849) to proceed with enrollment. This phase III, open-label controlled clinical trial studied the antitumor effects of intravesical administration of nadofaragene firadenovec to 157 individuals with NIMBC, 62.4% of whom were also BCG-unresponsive. The treatment was delivered once every three months over the period of 12 months, although it was discontinued for a participant if they experienced intolerable toxicity or cancer recurrence. During the program, 51% of patients demonstrated a complete response (CR), which lasted the full year for 46% of the remaining participants. As with any other cancer therapy, duration of response (DoR) is another key endpoint; Adstiladrin’s efficacy demonstrated a median DoR of 9.7 months. Some of the most common adverse events, at an incidence rate of 10% or more, were chills, fatigue, and bladder spasm. Laboratory abnormalities occurring in greater than 15% of participants included elevated glucose, elevated triglycerides, and hematuria.

What’s Next for Adstiladrin?

The FDA recommends delivering 75 mL of Adstiladrin at a concentration of 3 x 1011 vp/mL to patients once every three months using a urinary catheter to target bladder cancer cells. For full consumer prescribing information, visit the product monograph here. The remaining participants of Study CS-003 will progress through the 60-month safety follow-up period, which will reach completion likely by June 2023. After reaching this critical milestone, Ferrin will pioneer the large-scale commercial production of vector therapy in the field of oncology. Adstiladrin is expected to become available for superficial bladder cancer patients on the market by late 2023.

A Trusted CRO for Oncology Clinical Trials

Vial CRO’s mission as a modern, next-generation contract research organization (CRO) is to support sponsors around the globe with our innovative tech-enabled clinical trial management services. Vial is a global, full-service CRO and a trusted partner for biotech and biopharma companies looking to manage clinical trials across multiple therapeutic areas, including oncology. To learn more about how our CRO’s products and services can help your clinical trial reach its full potential, connect with a team member today!

Contact Us

By submitting, you are agreeing to our terms and privacy policy
This field is for validation purposes and should be left unchanged.