Patients with Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer in Europe may soon have a new bladder-sparing treatment option after the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) backed conditional approval of Adstiladrin (nadofaragene firadenovec, Ferring Pharmaceuticals), a gene therapy, as monotherapy for adults with carcinoma in situ, with or without papillary tumors. 

For clinicians, the significance is straightforward: Once BCG fails, treatment options are limited, recurrence and progression are common, and many patients ultimately face radical cystectomy. The positive CHMP opinion followed assessment by the Committee for Advanced Therapies.

How the Therapy Works 

Nadofaragene firadenovec is a nonreplicating, recombinant type 5 adenovirus vector-based gene therapy that contains the human interferon alfa-2b transgene. After intravesical administration, viral particles enter tumor cells and bladder urothelium, leading to interferon alfa-2b protein expression that activates an antitumor immune response.

Clinical Data 

The CHMP’s recommendation was based on evidence from a single-arm, multicenter study that showed a 53.4% complete response rate (median duration of response, 9.7 months) in the target population of 103 patients. 

Long-term follow-up data from a phase 3 trial also supported durability and safety. The study enrolled 157 patients, of whom 151 were included in efficacy analyses. At 60 months, nadofaragene firadenovec allowed bladder preservation in nearly half of patients, with cystectomy-free survival of 49% in the overall population. Median follow-up was 50.8 months.

Administration and Safety 

If authorized by the European Commission, the therapy will be available as a 3 × 10¹¹ viral particles/mL intravesical suspension. Treatment must be started and administered in clinical centers under the supervision of physicians experienced in managing patients with non-muscle invasive bladder cancer.

The most common side effects were instillation site discharge, bladder spasm, micturition urgency, hematuria, dysuria, urinary tract infection, lower urinary tract pain, pollakiuria, fatigue, pyrexia, chills, headache, and diarrhea. 

Long-term safety data were reassuring. Most adverse events were grade 1 or 2, with 3.8% of patients reporting grade 3 events and no patients experiencing grades 4 or 5 study drug-related adverse events. No new safety signals emerged with extended follow-up, and no deaths were attributed to the study drug.

What Happens Next 

Detailed prescribing recommendations will be described in the summary of product characteristics, which will be published on the European Medicines Agency website in all official European Union languages after marketing authorization is granted by the European Commission. 

Because the CHMP backed conditional authorization, the manufacturer will still be required to provide additional clinical data.