Ferring Pharmaceuticals is broadening the clinical development of nadofaragene firadenovec (ADSTILADRIN®) to address various stages and types of urothelial cancer. This includes initiating new studies in intermediate-risk non-muscle invasive bladder cancer (NMIBC) and low-grade upper tract urothelial cancer (UTUC), alongside ongoing research in high-risk Bacillus Calmette-Guérin (BCG)-unresponsive NMIBC.
These efforts aim to provide more treatment options and improve outcomes for patients with these challenging conditions.
Clinical Trials Expansion
Ferring has activated sites for the ABLE-22 and ABLE-32 trials, and initiated the LUNAR trial to investigate nadofaragene firadenovec in different urothelial cancer settings.
- ABLE-22 (NCT06545955): This Phase 2 trial is designed for high-risk BCG-unresponsive NMIBC. It will evaluate nadofaragene firadenovec as a monotherapy and in combination with chemotherapy (gemcitabine and docetaxel) or an immune checkpoint inhibitor (pembrolizumab). A key feature of this trial is the option for re-induction with a second dose of nadofaragene firadenovec for patients who do not achieve a complete response after the initial treatment.
- ABLE-32 (NCT06510374): This Phase 3B trial is focused on intermediate-risk NMIBC (IR NMIBC), a space where there are currently no FDA-approved treatment options. The trial will assess the efficacy and safety of nadofaragene firadenovec compared to observation following transurethral resection of bladder tumor (TURBT). The primary endpoint is recurrence-free survival (RFS).
- LUNAR (NCT06668493): This Phase 1-2 trial is evaluating the safety, tolerability, and efficacy of nadofaragene firadenovec in patients with low-grade UTUC (LG UTUC). The treatment will be administered directly to the renal pelvis. The trial includes a safety lead-in period for the first six patients.
Rationale for the Studies
The expansion of the nadofaragene firadenovec clinical trial program is driven by the need for more effective and organ-sparing treatments for NMIBC and UTUC. According to Joern Jakobsen, M.D., Ph.D., Vice President and Head of Global Research and Medical for Uro-Oncology and Urology at Ferring Pharmaceuticals, this expansion is "key to understanding how ADSTILADRIN may be able to help even more patients."
The decision to formalize the collection of re-induction data in the ABLE-22 trial reflects a commitment to exploring strategies that could potentially offer more patients the opportunity to preserve their bladder and avoid radical surgery.
About Nadofaragene Firadenovec
Nadofaragene firadenovec (ADSTILADRIN®) is the first and only FDA-approved intravesical non-replicating gene therapy for the treatment of adult patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors. It works by delivering the gene for interferon alfa-2b directly into the cells of the bladder wall, turning them into interferon microfactories that enhance the body’s natural defenses against cancer.
Disease Burden and Current Treatment Landscape
NMIBC is a common form of bladder cancer, accounting for approximately 75% of bladder cancer cases. In the United States, bladder cancer is the sixth most common cancer, with an estimated 83,190 new cases expected in 2024. While intravesical BCG is the first-line standard of care for high-risk NMIBC, a significant proportion of patients do not respond to BCG therapy or experience recurrence or progression of their disease. For these patients, treatment options are limited, and cystectomy is often recommended.
UTUC accounts for about 10% of all urothelial cancers. Low-grade tumors comprise all low-risk and some high-risk tumors in UTUC, with management goals including treatment of visible tumors and preservation of the urinary tract. There is an estimated total incidence of just over 7,000 new UTUC cases each year in the U.S., and the prevalence appears to be increasing.
