Adstiladrin (nadofaragene firadenovec-vncg) / Ferring, FKD Therapies, Royalty - LARVOL DELTA

Advancements in bladder cancer immunotherapy: a focus on intravesical approaches. (PubMed, Front Pharmacol) - "Novel combinations, such as sasanlimab (a PD-1 monoclonal antibody) with BCG, have improved event-free survival in high-risk non-muscle-invasive bladder cancer (NMIBC). Intravesical anti-PD-1/PD-L1 agents like pembrolizumab and nadofaragene firadenovec have demonstrated efficacy and safety in BCG-unresponsive NMIBC, leading to regulatory approval. Additionally, BCG combined with immunostimulatory protein complexes (e.g., N-803) achieved high complete response rates while preserving quality of life...Promising results have also been observed with intravesical oncolytic immunotherapy combined with systemic anti-PD-1 therapy in cisplatin-ineligible MIBC. These advancements underscore the potential of intravesical and systemic immunotherapies to improve bladder cancer outcomes and warrant further investigation."

Journal • Review • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Nadofaragene firadenovec: “The CHMP was updated on the discussions at the CAT. The committee discussed the issues identified in this application”; Muscle invasive bladder cancer (European Medicines Agency) - CHMP Final Minutes of the meeting on 22 - 25 Apr 2025: “The committee adopted the CHMP recommendation and scientific discussion together with the list of questions as adopted by CAT”

CHMP • Bladder Cancer • Oncology

Safety and Efficacy of FE 999326 Administered Intravesically to Japanese Subjects With High-grade, BCG Unresponsive, Non-muscle Invasive Bladder Cancer (NMIBC) (clinicaltrials.gov) - P3 | N=25 | Active, not recruiting | Sponsor: Ferring Pharmaceuticals | Trial primary completion date: Oct 2025 ➔ Nov 2029

Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

ABLE-41: ADSTILADRIN Early Utilization and Outcomes in the Real World Setting (clinicaltrials.gov) - P=N/A | N=400 | Recruiting | Sponsor: Ferring Pharmaceuticals | Trial completion date: Dec 2025 ➔ Dec 2027 | Trial primary completion date: Dec 2025 ➔ Dec 2027

Real-world evidence • Trial completion date • Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Outcomes of Reinduction With Nadofaragene Firadenovec. (PubMed, J Urol) - No abstract available

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

IP02-36 Use of Rectal Diazepam to Prevent Bladder Spasms and Leakage of Medication During Intravesical Administration of Nadofaragene Firadenovec in BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer: Erratum. (PubMed, J Urol) - No abstract available

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Intravesical interferon-α2b gene therapy with nadofaragene firadenovec-vncg: a contemporary review. (PubMed, Future Oncol) - "Today, nadofaragene firadenovec-vncg represents the first-line treatment option for patients with BCG-unresponsive disease as an alternative to cystectomy. Advances in our knowledge of the tumor microenvironment, gene therapy techniques, and tumor biology have contributed to this important discovery, with future studies aimed to optimize the efficacy of this therapy through improved patient selection, disease prognostication, and development of combination strategies."

Journal • Review • Bladder Cancer • Gene Therapies • Genito-urinary Cancer • Oncology • Solid Tumor

ABLE-22: A Trial to Evaluate Intravesical Nadofaragene Firadenovec Alone or in Combination With Chemotherapy or Immunotherapy in Participants With High-grade BCG Unresponsive Non-muscle Invasive Bladder Cancer (clinicaltrials.gov) - P3 | N=250 | Recruiting | Sponsor: Ferring Pharmaceuticals | Trial primary completion date: Dec 2030 ➔ Jun 2028

Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Emerging bladder-sparing treatments for high risk non-muscle invasive bladder cancer. (PubMed, Bladder Cancer) - "Emerging BSTs include immune checkpoint inhibitors like pembrolizumab and novel agents such as nadofaragene firadenovec and nogapendekin alfa inbakicept (IL-15)...Gene therapies and targeted agents like CG0070 and EG-70 are also gaining traction for their innovative mechanisms...Despite advancements, challenges remain in balancing efficacy, safety, and cost-effectiveness within diverse healthcare settings. This narrative review highlights the evolving landscape of BSTs for HR-NMIBC, emphasising the need for robust clinical evidence to refine patient selection and optimise outcomes."

Journal • Review • Bladder Cancer • Gene Therapies • Genito-urinary Cancer • Oncology • Solid Tumor • IL15

Use of Rectal Diazepam to Prevent Bladder Spasms and Leakage of Medication During Intravesical Administration of Nadofaragene Firadenovec for BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer. (PubMed, J Urol) - "Rectal diazepam pretreatment may reduce bladder spasms and improve nadofaragene firadenovec retention during intravesical instillation, thereby enhancing efficacy. Rectal diazepam could improve patient comfort and treatment outcomes, thus warranting further investigation through larger, prospective studies."

Journal • Bladder Cancer • Fatigue • Genito-urinary Cancer • Oncology • Solid Tumor

LUNAR: Low-grade UTUC Treated With Nadofaragene Firadenovec Administered to Renal Pelvis (clinicaltrials.gov) - P1/2 | N=20 | Recruiting | Sponsor: Ferring Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Solid Tumor • Urothelial Cancer

Novel inhibitors of mitochondrial permeability transition pore block platelet procoagulant activity (ISTH 2025) - "The mitochondrial permeability transition pore (mPTP) facilitates PS exposure, but traditional modulators like cyclosporine A (CsA) lack specificity as direct inhibitors. MC63 and TR002 had no effects on platelet aggregation. Western blot demonstrated that MC63 and TR002 enhanced phosphorylation of Bcl-xL and Akt substrates in the presence of calcium, suggesting a role for Bcl-xL stabilization and anti-apoptotic Akt signaling in mediating the effects of MC63 and TR002 on platelet procoagulant activity."

Cardiovascular • Hematological Disorders • Thrombosis • BCL2L1

ABLE-41, a real-world evidence study for bladder cancer patients treated with nadofaragene firadenovec: Baseline patient characteristics and demographics. (ASCO 2025) - P | "Early data from the real-world usage of nadofaragene firadenovec in this study demonstrates patients are older than those in the phase 3 trial but despite having 1 subject with ECOG status > 2, they self-report low levels of pain and limitations on daily living activities. Inclusion of patients outside the FDA label and clinical guidelines may provide unique insights and hypothesis generation."

Clinical • HEOR • Real-world • Real-world evidence • Bladder Cancer • CNS Disorders • Depression • Gene Therapies • Genito-urinary Cancer • Mood Disorders • Oncology • Pain • Psychiatry • Solid Tumor

ABLE-32: A randomized, controlled, phase 3b clinical trial of nadofaragene firadenovec-vncg versus observation in patients with intermediate-risk non–muscle-invasive bladder cancer. (ASCO 2025) - P3 | "Exploratory endpoints include effect on potential biomarkers and health-related quality of life. Final results are expected in 2031."

Clinical • P3 data • Bladder Cancer • Gene Therapies • Genito-urinary Cancer • Oncology • Solid Tumor

ABLE-22: Safety and efficacy evaluation of nadofaragene firadenovec alone or in combination with chemotherapy or immunotherapy—A randomized, open-label, phase 2 study. (ASCO 2025) - P3 | "Bladder-preserving treatment options for patients with BCG-unresponsive NMIBC with CIS ± Ta/T1 include intravesical gene therapy (nadofaragene firadenovec-vncg), intravesical chemotherapy (gemcitabine and docetaxel), and immunotherapy (intravenous pembrolizumab and intravesical nogapendekin alfa inbakicept-pmln). Exploratory endpoints include changes in expression of potential biomarkers in blood and urine. Results from this investigational, randomized, multicenter, open-label study evaluating the safety and efficacy of nadofaragene firadenovec alone or in combination with chemotherapy or immunotherapy are expected July 2028."

Clinical • Combination therapy • IO biomarker • P2 data • Bladder Cancer • Gene Therapies • Genito-urinary Cancer • Oncology • Solid Tumor

ABLE-22: A Trial to Evaluate Intravesical Nadofaragene Firadenovec Alone or in Combination With Chemotherapy or Immunotherapy in Participants With High-grade BCG Unresponsive Non-muscle Invasive Bladder Cancer (clinicaltrials.gov) - P3 | N=250 | Recruiting | Sponsor: Ferring Pharmaceuticals | Phase classification: P2 ➔ P3 | N=150 ➔ 250

Enrollment change • Phase classification • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Real-World Outcomes With Nadofaragene in BCG-Unresponsive NMIBC (Urology Times) - "A recent study by Moyer et al (2025) provides real-world data on the efficacy and safety of nadofaragene firadenovec in patients with BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC). Conducted across 3 Mayo Clinic sites between November 2023 and October 2024, the study included 45 patients, with 29 evaluable for efficacy analysis. The median follow-up was 8.2 months.​..Complete Response / High-Grade Recurrence-Free Survival: At 3 months: 72%; At 6 months: 62%...Cystectomy-Free Survival: At 6 months: 94%; Overall Survival: At 6 months: 100%; Adverse Events: Bladder spasms: 62%...These findings suggest that nadofaragene firadenovec offers promising efficacy and a favorable safety profile for patients with BCG-unresponsive NMIBC....This study contributes valuable real-world evidence to the existing clinical data on nadofaragene firadenovec, supporting its role as a viable treatment option for this patient population."

Real-world evidence • Bladder Cancer

Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer, a study with 5-year follow-up: a plain language summary. (PubMed, Future Oncol) - No abstract available

Journal • Bladder Cancer • Gene Therapies • Genito-urinary Cancer • Oncology • Solid Tumor

Matching-Adjusted Indirect Comparisons (MAIC) of TAR-200 vs FDA Approved Novel Agents in Bacillus Calmette-Guerin (BCG) Unresponsive High-Risk (HR) Non-Muscle Invasive Bladder Cancer (NMIBC) with Carcinoma in Situ (CIS) (ISPOR 2025) - "OBJECTIVES: FDA has approved pembrolizumab (pembro), nadofaragene firadenovec-vncg (nadofaragene), and nogapendekin alfa inbakicept-pmln (NAI) + BCG for the treatment of patients with BCG-unresponsive HR NMIBC with CIS. TAR-200 demonstrated statistically significant clinical benefit in CR rate at any time over FDA approved novel agents in BCG-unresponsive HR NMIBC with CIS and at first disease assessment compared to NAI + BCG. Further analyses will be conducted once additional follow-up is available for TAR-200."

Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

ABLE-32: Trial of Nadofaragene Firadenovec vs. Observation in Participants With Intermediate Risk Non-Muscle Invasive Bladder Cancer (clinicaltrials.gov) - P3 | N=454 | Recruiting | Sponsor: Ferring Pharmaceuticals | Trial completion date: Jun 2031 ➔ Mar 2030 | Trial primary completion date: Aug 2028 ➔ Mar 2030

Trial completion date • Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

ABLE-22: A Trial to Evaluate Intravesical Nadofaragene Firadenovec Alone or in Combination With Chemotherapy or Immunotherapy in Participants With High-grade BCG Unresponsive Non-muscle Invasive Bladder Cancer (clinicaltrials.gov) - P2 | N=150 | Recruiting | Sponsor: Ferring Pharmaceuticals | Trial completion date: Jul 2028 ➔ Dec 2030 | Trial primary completion date: Jul 2026 ➔ Dec 2030

Trial completion date • Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Current State of Bladder Preservation in High Grade Non-Muscle Invasive Bladder Cancer and Localized Muscle Invasive Bladder Cancer. (PubMed, Curr Oncol Rep) - "Approved novel therapies, including systemic pembrolizumab and intravesical agents such as nadofaragene, nogapendekin alfa inbakicept, and cretostimogene grenadenorepvec, have shown promising results for BCG-unresponsive NMIBC patients. Promising novel therapies, such as immunotherapy, recombinant intravesical therapies, and antibody-drug conjugates are emerging as potential alternatives. These therapies aim to achieve good oncological outcomes while maintaining quality of life, providing an alternative to the decades long standard of care."

Journal • Review • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Intravesical instillation of a TME engineering viral vector increases survival in an orthotropic bladder cancer model (AACR 2025) - "Non-muscle invasive urinary bladder cancer is currently treated with bacillus Calmette-Guérin (BCG) instillations followed by nadofaragene firadenovec-vncg for BCG refractory patients...We hypothesize that LOAd703, the human equivalent to Adm703, may be an interesting option for these patients...In conclusion, TME gene engineering with TMZ-CD40L and 4-1BBL increased survival of mice with orthotopic bladder cancer. Further studies investigating Adm703's effect on the immune system are planned."

Preclinical • Viral vector • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • CD40LG

U.S. FDA Approves Second Drug Product Manufacturing Facility for ADSTILADRIN (nadofaragene firadenovec-vncg) (Businesswire) - "Ferring Pharmaceuticals announced today the U.S. Food and Drug Administration (FDA) approved a state-of-the-art drug product manufacturing hub in Parsippany, NJ, for its intravesical non-replicating gene therapy ADSTILADRIN (nadofaragene firadenovec-vncg). The approval expands Ferring’s manufacturing capabilities to three cutting-edge sites dedicated to bringing ADSTILADRIN to patients and secures a final $200 million payment from Royalty Pharma (Nasdaq: RPRX) as part of a royalty-based financing agreement announced in 2023....'This expansion and diversification of our manufacturing footprint will further ensure stable and sustainable supply of ADSTILADRIN to meet the anticipated growth in global demand.'"

Commercial • Bladder Cancer

Final Five-Year Analysis of Phase 3 Data With ADSTILADRIN (nadofaragene firadenovec-vncg) Shows Durable Bladder Preservation and Consistent Long-Term Safety in BCG-unresponsive NMIBC (Businesswire) - P3 | N=157 | NCT02773849 | Sponsor: Ferring Pharmaceuticals | "Ferring Pharmaceuticals today announced the final 60-month follow-up data from the Phase 3 study of ADSTILADRIN (nadofaragene firadenovec-vncg) were presented at the American Urological Association (AUA) 2024 Annual Meeting....Median follow-up was 50.8 months (IQR 39.1-60.0), with 26.8% receiving five instillations and 7.6% receiving treatment for 57 months. Among patients who were high-grade recurrence free (HGRF) at Month 3, 13 patients were followed and remained HGRF at month 57....The overall survival at 60 months was 76.3% in the CIS cohort and 85.9% in the PD cohort. The cystectomy-free survival rate at Month 60 was 43.2.% and 58.7% in the CIS and PD cohorts, respectively. Clinical progression to muscle invasion was rare in the trial population and seen in only 3.3% of all patients (four with CIS and one with Ta/T1) over the five-year follow-up period."

P3 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor