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FDA approves novel bladder cancer gene therapy treatment

The first gene therapy for treating a form of bladder cancer has been given the nod by the US Food & Drug Administration (FDA), after successful results from a multicentre clinical study, providing an alternative to those who previously had limited treatment options other than bladder removal surgery.

Medpage Today reports that the adenoviral vector-based product adofaragene firadenovec (Adstiladrin) is specifically for high-risk bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC), indicated for adult patients with carcinoma in situ (CIS) with or without papillary tumours.

Approval was based on results from from the study of 157 patients with high-risk BCG-unresponsive NMIBC, 98 of whom had BCG-unresponsive CIS with or without papillary tumours and could be evaluated for response.

“Patients with BCG-unresponsive NMIBC have historically had limited treatment options other than bladder removal surgery,” said lead investigator Dr Stephen Boorjian of the Mayo Clinic in Minnesota. This approval is “a significant advance in the current treatment landscape and provides a novel treatment option for patients”.

In the study, patients received nadofaragene firadenovec once every three months for up to 12 months, or until unacceptable toxicity to therapy or recurrent high-grade NMIBC. The complete response (CR) rate was 51% at three months, with about half of these responding patients remaining in CR for at least one year. The median duration of response was 9.7 months.

“This approval provides healthcare professionals with an innovative treatment option for patients with high-risk non-muscle-invasive bladder cancer that is unresponsive to BCG therapy,” said Dr Peter Marks, director of the FDA’s Centre for Biologics Evaluation and Research.

Nadofaragene firadenovec is a non-replicating adenovirus vector-based therapy containing the interferon alfa-2b gene. As described by developer Ferring Pharmaceuticals, the vector enters the cells of the bladder wall and releases the interferon alfa-2b gene.

“The internal gene/DNA machinery of the cells ‘picks up’ the gene and translates its DNA sequence, resulting in the cells secreting high quantities of interferon alfa-2b protein, a naturally occurring protein the body uses to fight cancer,” said the company.

The product is administered three-monthly into the bladder via a urinary catheter, and is not indicated for people who are immunosuppressed or immune-deficient.

Ferring expects nadofaragene firadenovec to be commercially available in the US in the second half of 2023.

Study details

ADSTILADRIN (=INSTILADRIN) in Patients With High Grade, Bacillus Calmette-Guerin (BCG) Unresponsive Non-Muscle Invasive Bladder Cancer (NMIBC)

Stephen Boorjian, Society of Urologic Oncology Clinical Trials Consortium

Published on National Library of Medicine website on 5 December 2022


Previous multi-dose Phase I and Phase II clinical studies have demonstrated that ADSTILADRIN is a safe and effective treatment for BCG-refractory and recurrent NMIBC. This Phase III study is designed to expand those observations using a high dose of ADSTILADRIN in patients that are "BCG Unresponsive" which refers to patients with high-grade NMIBC who are unlikely to benefit from and should not receive further intravesical BCG.


Recombinant IFN alpha2b has pleiotropic effects that contribute to antitumor activity in Non-Muscle Invasive Bladder Cancer (NMIBC). ADSTILADRIN is a non-replicating adenovirus vector harboring the human IFN alpha2b gene. When combined with the excipient Syn3, intravesical administration of the rAd-IFN results in transduction of the virus into the epithelial cell lining in the bladder. The IFN alpha2b gene is incorporated into the cellular DNA resulting in the synthesis and expression of large amounts of IFN alpha2b protein. Clinical studies have confirmed that IFN alpha2b protein can be measured in the urine of patients treated with ADSTILADRIN within 24 hours after dosing.


NIH article – ADSTILADRIN (=INSTILADRIN) in Patients With High Grade, Bacillus Calmette-Guerin (BCG) Unresponsive Non-Muscle Invasive Bladder Cancer (NMIBC) (Open access)


MedPage Today article – FDA Approves First Gene Therapy for Non-Muscle-Invasive Bladder Cancer (Open access)


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FDA approves Merck’s Ketruda — first new treatment for bladder cancer in 20 years


New immunotherapy prolongs bladder cancer and melanoma patients’ lives


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