Nadofaragene firadenovec
- Generic Name
- Nadofaragene firadenovec
- Brand Names
- Adstiladrin
- Drug Type
- Biotech
- CAS Number
- 1823059-12-6
- Unique Ingredient Identifier
- 0OOS09O1FH
- Background
Nadofaragene firadenovec (nadofaragene firadenovec-vncg) is a recombinant non-replicating adenovirus serotype 5 vector containing a transgene encoding human interferon alfa-2b (IFNα2b). It was approved by the FDA on December 2022 for the treatment of high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors. It is the first gene therapy approved by the FDA for the treatment of bladder cancer.
BCG-unresponsive NMIBC has a high recurrence and is notably difficult to treat. Most patients with this condition undergo radical cystectomy since other non-surgical treatments are far less effective. The use of nadofaragene firadenovec provides a therapeutic alternative to patients seeking non-surgical alternatives for the treatment of BCG-unresponsive NMIBC. Nadofaragene firadenovec is formulated with an excipient (Syn-3) that facilitates gene transfer across the urothelium and promotes the transduction of IFNα2b. The localized expression of this gene induces anti-tumor effects. Nadofaragene firadenovec also has a manageable adverse event profile. Compared to pembrolizumab, a smaller proportion of patients experienced grade 3-4 adverse events (4% vs 12.7%).
- Indication
Nadofaragene firadenovec is indicated for the treatment of adult patients with high-risk Bacillus CalmetteGuérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors.
- Associated Conditions
- High risk BCG-unresponsive non-muscle invasive bladder cancer
FDA Approves Ferring Pharmaceuticals' New Manufacturing Facility for Bladder Cancer Gene Therapy ADSTILADRIN
• The FDA has approved Ferring Pharmaceuticals' new drug product manufacturing hub in Parsippany, NJ, for production of ADSTILADRIN, the first FDA-approved intravesical gene therapy for high-risk BCG-unresponsive bladder cancer.
• The approval expands Ferring's manufacturing capabilities to three sites dedicated to ADSTILADRIN production, triggering a final $200 million payment from Royalty Pharma as part of a financing agreement announced in 2023.
• The 12,000 square foot state-of-the-art facility features renewable energy solutions and specialized technology to ensure stable supply for growing global demand, reinforcing Ferring's commitment to uro-oncology treatment innovation.
Nadofaragene Firadenovec Shows 75% Complete Response Rate in Japanese Phase 3 Trial for BCG-Unresponsive Bladder Cancer
• Nadofaragene firadenovec demonstrated a 75% complete response rate at 3 months in Japanese patients with high-risk BCG-unresponsive non-muscle invasive bladder cancer with carcinoma in situ, according to new Phase 3 trial data.
• The gene therapy showed a favorable safety profile with 84.2% of treatment-related adverse events being Grade 1 and 15.8% Grade 2, with no Grade 3 or higher events reported in the Japanese patient population.
• These results appear higher than previously reported in US trials and align with recent Mayo Clinic real-world data showing a 79% complete response rate, potentially establishing nadofaragene as a new standard of care for patients who would otherwise face bladder removal.
Novel BCMA-Directed CAR T-Cell Therapy Shows Promising Efficacy in Relapsed/Refractory Multiple Myeloma and AL Amyloidosis
• A second-generation BCMA-directed CAR T-cell therapy, MDC-CAR-BCMA001, demonstrated remarkable efficacy in patients with relapsed/refractory multiple myeloma and AL amyloidosis, achieving a 5/6 overall response rate with 4 complete responses.
• The novel therapy showed a favorable safety profile with manageable toxicity, including low incidence of severe cytokine release syndrome and no neurotoxicity, even in patients with significant organ dysfunction.
• These promising results have prompted further investigation through ongoing clinical trials, including CARLOTTA001 (NCT05836896) and the CLEAR AL trial, potentially offering new hope for difficult-to-treat hematologic malignancies.
BCG Shortage Continues to Shape Bladder Cancer Treatment Landscape Despite New Therapy Approvals
• The recent FDA approval of nogapendekin alfa inbakicept plus BCG for BCG-unresponsive bladder cancer faces implementation challenges due to ongoing BCG supply shortages across U.S. healthcare facilities.
• Healthcare providers are adapting treatment strategies through split-dose BCG regimens and exploring alternative therapies, including nadofaragene firadenovec which offers convenient quarterly dosing schedules.
• Novel diagnostic tools, including AI-powered pathology analysis and urinary cell-free DNA testing, are emerging as promising approaches for improving treatment selection and monitoring in bladder cancer.
ImmunityBio's Anktiva Pursues European and UK Approval for BCG-Unresponsive Bladder Cancer
• ImmunityBio's Anktiva, combined with BCG, seeks approval in the EU and UK for treating BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS).
• The MAAs submitted to the EMA and MHRA are supported by Phase 2/3 QUILT-3.032 trial data, demonstrating a 71% complete response rate in patients with NMIBC with CIS.
• Regulatory assessments by both agencies are anticipated to conclude by Q4 2025, potentially leading to approval in Europe and the UK by 2026, expanding global access.
• ImmunityBio also plans to submit a supplemental BLA to the FDA in 2025, seeking approval for Anktiva in patients with BCG-unresponsive NMIBC in the papillary indication.
J&J Seeks FDA Approval for TAR-200 in BCG-Unresponsive Non-Muscle Invasive Bladder Cancer
• Johnson & Johnson has initiated a New Drug Application (NDA) submission to the FDA for TAR-200.
• TAR-200 is intended for patients with Bacillus Calmette-Guérin (BCG)-unresponsive high-risk non-muscle-invasive bladder cancer (HR-NMIBC).
• Phase 2b SunRISe-1 study data showed an 83.5% complete response rate with TAR-200 monotherapy.
• The FDA is reviewing the application under the Real-Time Oncology Review (RTOR) program to expedite potential approval.
FDA Approves ImmunityBio's Bladder Cancer Drug After Second Review
The FDA has approved ImmunityBio's Anktiva, a treatment for non-muscle invasive bladder cancer (NMIBC) that did not respond to BCG vaccine alone, marking the company's first commercial-stage product. This decision comes after initial rejection due to manufacturing quality issues.
Verastem's Avutometinib and Defactinib Combination Receives FDA Priority Review for Recurrent KRAS Mutant Low-Grade Serous Ovarian Cancer
• The FDA has granted Priority Review to Verastem Oncology's NDA for avutometinib combined with defactinib for recurrent KRAS mutant low-grade serous ovarian cancer (LGSOC).
• The PDUFA target action date is set for June 30, 2025, with the FDA indicating that an advisory committee meeting is not currently planned.
• The NDA is supported by Phase 2 RAMP 201 trial data, demonstrating substantial overall response rates and durable responses in patients with recurrent KRAS mutant LGSOC.
• If approved, this combination therapy would be the first FDA-approved treatment specifically for adults with recurrent KRAS mutant LGSOC, addressing a significant unmet need.
FDA Approvals in 2024: Advancing Treatment Paradigms in Solid Tumors and Hematologic Malignancies
• The FDA granted over 65 approvals in 2024, significantly impacting treatment paradigms across various cancers, including breast, gynecologic, skin, and genitourinary malignancies.
• Several tumor-agnostic approvals, such as fam-trastuzumab deruxtecan-nxki (Enhertu) for HER2-positive solid tumors and repotrectinib (Augtyro) for NTRK fusion-positive tumors, marked advancements in precision medicine.
• Immunotherapies like nivolumab (Opdivo) and pembrolizumab (Keytruda) received multiple approvals, including combinations with chemotherapy for urothelial and endometrial carcinomas, improving patient outcomes.
• Targeted therapies like vorasidenib (Voranigo) for low-grade glioma and selpercatinib (Retevmo) for RET-mutated thyroid cancers addressed unmet needs and demonstrated high efficacy and tolerability.
Nadofaragene Firadenovec Shows Promise in BCG-Unresponsive Bladder Cancer, Reducing Cystectomy Rates
• Phase 3 trial data reveals that approximately two-thirds of patients achieving a complete response with nadofaragene firadenovec remained cystectomy-free at 60 months.
• Among patients undergoing cystectomy post-nadofaragene, a minority (about 6 out of 37) exhibited muscle-invasive bladder cancer, indicating potential in delaying progression.
• Nadofaragene firadenovec can be considered as a viable option for treating patients with BCG-unresponsive non-muscle-invasive bladder cancer.
• The study followed patients for up to 60 months to assess long-term outcomes and the need for radical cystectomy.
Durvalumab Gains Priority Review for Muscle-Invasive Bladder Cancer Treatment
• The FDA has granted priority review to durvalumab (Imfinzi) for muscle-invasive bladder cancer (MIBC), potentially expediting its approval.
• Phase 3 NIAGARA trial data supports the application, showing a 32% reduction in disease progression or recurrence with perioperative durvalumab.
• The Imfinzi regimen also demonstrated a 25% reduction in the risk of death, offering a significant survival benefit.
• Regulatory decisions are anticipated in the second quarter of 2025, with potential implications for MIBC treatment standards.
Real-World Data and Ongoing Trials Highlight Efficacy of Nadofaragene Firadenovec in Bladder Cancer
• Real-world data presented at the 2025 ASCO Genitourinary Cancers Symposium indicates nadofaragene firadenovec demonstrates positive efficacy and safety outcomes in treating NMIBC.
• The ABLE-32 phase 3B trial is underway to assess nadofaragene firadenovec in intermediate-risk NMIBC patients, addressing the unmet need for FDA-approved treatments.
• Additional trials, including ABLE-22 and LUNAR, are exploring nadofaragene firadenovec as a monotherapy, in combination with other treatments, and in low-grade upper tract urothelial carcinoma.
• Nadofaragene firadenovec, the first FDA-approved intravesical gene therapy, offers a novel approach by turning bladder wall cells into interferon microfactories to fight cancer.
Ferring Advances Nadofaragene Firadenovec Clinical Program in Urothelial Cancers
• Ferring Pharmaceuticals is expanding the clinical trial program for nadofaragene firadenovec, an intravesical gene therapy, to include intermediate-risk NMIBC and low-grade UTUC.
• A Phase 2 trial (ABLE-22) will evaluate nadofaragene firadenovec alone or with chemotherapy/immunotherapy in high-risk BCG-unresponsive NMIBC, including re-induction for non-responders.
• The Phase 3B ABLE-32 trial will assess nadofaragene firadenovec in intermediate-risk NMIBC, an area with no FDA-approved treatments, using recurrence-free survival as the primary endpoint.
• The LUNAR trial is initiated to study nadofaragene firadenovec in patients with low-grade upper tract urothelial cancer (UTUC), addressing a significant unmet need.
Detalimogene Voraplasmid and Gemcitabine Combinations Show Promise in Bladder Cancer Trials
• Detalimogene voraplasmid (EG-70) shows a 71% any-time complete response rate in BCG-unresponsive NMIBC patients with carcinoma in situ in the LEGEND trial.
• Gemcitabine and docetaxel combination demonstrates a 92% complete response rate at 12 months in BCG-naive, high-risk NMIBC patients.
• Gemcitabine-BCG combination shows a 94% complete response rate at 6 months in BCG-exposed NMIBC, suggesting enhanced efficacy and safety.
• Studies highlight the potential of novel intravesical therapies to improve outcomes and reduce the need for radical cystectomy in bladder cancer.
Novel Agents Show Promise in BCG-Unresponsive NMIBC Treatment
• TAR-200 monotherapy demonstrated an 83.5% complete response rate in the SunRISe-1 trial, with an estimated 12-month duration of response rate of 65.7%.
• Pembrolizumab monotherapy in the KEYNOTE-057 trial achieved a 41% complete response rate at 3 months in high-risk NMIBC patients without carcinoma in situ.
• Nadofaragene firadenovec-vncg showed a 53.4% complete response rate at 3 months and 45.5% at 1 year in a phase 3 trial for BCG-unresponsive NMIBC.
• Nogapendekin alfa inbakicept-pmln plus BCG achieved a 71% complete response rate at any time, with a median follow-up of 23.9 months in the QUILT-3.032 trial.
Ferring Expands Adstiladrin Production Capacity with New Facility in Finland
• Ferring is expanding its manufacturing capabilities with a new 25,000 square meter facility in Finland to produce the drug substance for Adstiladrin.
• The expansion follows FDA approval of Ferring's scale-up process in June 2023 and a partnership with SK pharmteco to further increase manufacturing capacity.
• Adstiladrin, an adenovirus vector-based gene therapy, received FDA approval in 2022 as the first gene therapy for bladder cancer, administered via catheter directly into the bladder.
• Ferring is also nearing completion of a fill/finish plant in Parsippany, New Jersey, focused on final drug product manufacturing, with larger-scale production expected in the coming years.
FDA Approves ImmunityBio's Anktiva for Bladder Cancer Treatment
• The FDA has approved Anktiva, an immunotherapy agent developed by ImmunityBio, for bladder cancer patients who do not respond to standard Bacillus Calmette-Guerin (BCG) therapy.
• Clinical trials showed that Anktiva, used in conjunction with BCG, resulted in a 55% successful response rate at three months and 45% after one year in a group of patients.
• Anktiva mimics a type of cell that stimulates the immune system to produce memory killer T cells, which recognize and attack bladder cancer cells, offering a new treatment option.
• Experts note that while Anktiva presents a promising alternative, the current worldwide shortage of BCG could potentially limit the number of patients who can receive the treatment.
FDA Approves Nadofaragene Firadenovec for High-risk Non-Muscle Invasive Bladder Cancer
The FDA has approved nadofaragene firadenovec-vncg (Adstiladrin) as the first gene therapy for adult patients with high-risk Bacillus Calmette-Guérin (BCG)–unresponsive non–muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), offering a new treatment option beyond bladder removal surgery.
Drug Development Updates
Stay informed with timely notifications on clinical trials, regulatory changes, and research advancements related to this medication.
© Copyright 2025. All Rights Reserved by MedPath