Nadofaragene Firadenovec Now Fully Available for BCG-Unresponsive NMIBC

Illustration of human bladder © reineg - stock.adobe.com

• Nadofaragene firadenovec (Adstiladrin) is the first and only intravesical gene therapy to be approved by the FDA for adult patients with non-muscle invasive bladder cancer (NMIBC) who no longer respond to standard therapy.
• The therapy is now fully available across the United States and can be prescribed by healthcare providers to their patients with NMIBC with carcinoma in situ (CIS) with or without papillary tumors.
• The real-world evidence study titled ABLE-41 U.S. (NCT06026332) is evaluating nadofaragene firadenovec and currently enrolling patients.

Nadofaragene firadenovec-vncg is now fully available for adult patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive NMIBC with CIS with or without papillary tumors across the United States.¹

In December 2022, nadofaragene firadenovec was approved by the FDA based on findings from Study CS-003 (NCT02773849), an open-label, multicenter, single-arm, phase 3 trial in which nadofaragene firadenovec-vncg was effective and demonstrated a favorable risk profile.^2,3

In the study of 157 patients with high-risk BCG-unresponsive NMIBC with CIS with or without papillary tumors, complete responses (CRs) to the single intravesical 75 mL dose of nadofaragene firadenovec (3 × 1011 viral particles per mL) were reached in 51% (95% CI, 41%-61%) of patients with carcinoma in situCIS with or without concomitant high-grade Ta or T1 disease within 3 months. With this result, the primary end point of the study was met. Further, the median duration of response (DOR) was 9.7 months with nadofaragene firadenovec, and 46% of the patients who had a CR were high-grade recurrence-free at 12 months.⁴

Safety results showed that the most common grade 3/4 drug-related adverse event, which was seen in 2 patients, was micturition. Both of these events were grade 3, and no treatment-related deaths were seen during the study.

“From the day we received FDA approval, Ferring has been committed to making [nadofaragene firadenovec] available to every appropriate high-risk NMIBC patient quickly and responsibly, working collaboratively with the bladder cancer community to inform our approach,” said Bipin Dalmia, senior vice president, global head, uro-oncology franchise at Ferring Pharmaceuticals, in a press release.¹ “With our significant manufacturing investments, we have achieved full product supply ahead of schedule. We are therefore ending our [nadofaragene firadenovec] Early Experience Program and look forward to bringing this novel therapy to every patient who needs it.”

The ADSTILADRIN Early Experience Program was initiated by Ferring Pharmaceuticals in September 2023. The program included a mix of trial sites that participated in the phase 3 study of nadofaragene firadenovec, as well as community clinics with the highest number of appropriate patients with NMIBC. The temporary program can now be ended as full supply of the product is available ahead of schedule. This will dramatically increase patient access to the agent.

Further, the non-interventional ADSTILADRIN in BLadder CancEr” (ABLE-41) U.S. Real World Evidence (RWE) Study is evaluating early utilization, experiences, and outcomes of nadofaragene firadenovec in the routine care setting. The multicenter, prospective trial is ongoing and has an estimated enrollment of 800 patients aged 18 years and older.⁵

To be eligible for the study, patients must have been prescribed and scheduled treatment with nadofaragene firadenovec per physician discretion or have received the first instillation of nadofaragene firadenovecof the agent per physician discretion after September 5, 2023, but prior to site activation.

The primary end points of the trial include whether a patient with CIS achieves CR at the first evaluation from first nadofaragene firadenovec instillation or not, and whether or not they achieve a CR any time within 1 year of their first nadofaragene firadenovec instillation.

“[Nadofaragene firadenovec] represents an effective alternative therapy for patients with NMIBC who, historically, had very few options once they no longer responded to standard BCG therapy,” said Andrea Maddox-Smith, chief executive officer of the Bladder Cancer Advocacy Network, BCAN, in a press release.¹ “Increasing access to this innovative therapy offers the potential of what patients need most – safe, effective treatment options that bring hope.”

REFERENCES:

1. Ferring announces full availability of ADSTILADRIN® (nadofaragene firadenovec-vncg) in the U.S. News release. Ferring Pharmaceuticals. January 16, 2024. Accessed January 16, 2024. http://tinyurl.com/7dy6nmd9

2. Ferring receives approval from U.S. FDA for Adstiladrin for high-risk, BCG-unresponsive non-muscle invasive bladder cancer. News release. Ferring Pharmaceuticals. December 16, 2022. Accessed January 16, 2024. https://bit.ly/3YxyWdY

3. FDA Approves first gene therapy for the treatment of high-risk, non-muscle-invasive bladder cancer. News release. FDA.gov. December 16, 2022. Accessed January 16, 2024. https://bit.ly/3HNUI7t

4. Boorjian SA, Alemozaffar M, Konety BR, et al. Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial. Lancet Oncol. 2021;22(1):107-117. doi:10.1016/S1470-2045(20)30540-4

5. ADSTILADRIN early utilization and outcomes in the real world setting in the united states (ABLE-41). ClinicalTrials.gov. Updated January 15, 2024. Accessed January 16, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT06026332