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DNA based therapy with diphtheria toxin-A BC-819: a phase 2b marker lesion trial in patients with intermediate risk nonmuscle invasive bladder cancer

J Urol. 2014 Jun;191(6):1697-702.

J Urol. 2014 Jun;191(6):1697-702.



H19 is a paternally imprinted oncofetal gene expressed in various embryonic tissues and in 85% of bladder tumors but suppressed in the adult healthy bladder. BC-819 is a DNA plasmid that carries the gene for diphtheria toxin-A under regulation of the H19 promoter sequence. We assessed the efficacy and toxicity of intravesical BC-819 instillations to prevent tumor recurrence and ablate a marker lesion in a phase 2b trial.


A total of 47 patients with recurrent, multiple nonmuscle invasive bladder tumors in whom prior intravesical therapy had failed underwent transurethral resection of all except 1 marker tumor. Patients expressing H19 received a 6-week induction course of intravesical BC-819. Patients who achieved a complete response (absent new tumors at 3 months) were given 3 maintenance courses of 3-weekly instillations every 3 months.


All patients were evaluable for adverse effects and 39 were evaluable for efficacy. Complete tumor ablation was achieved in 33% of patients and in 64% there were no new tumors at 3 months. Median time to recurrence was 11.3 months in all cases but significantly longer (22.1 months) when analyzed by response status at 3 months. Adverse events were mild. The study was limited by the small number of patients.


BC-819 prevented new tumor growth in two-thirds of the patients and ablated a third of the marker lesions. Prolonged time to recurrence was observed in responding patients. These results along with the good safety profile make BC-819 a potential medication for bladder cancer.

Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.


carcinoma; diphtheria toxin; plasmids; urinary bladder; urothelium

Comment from Maria Ribal: BC-819 is a plasmid comprised of the H19 gene regulatory sequences that drive the expression of Diphtheria Toxin A (DTA). It is being tested in phase II studies as intravesical therapy for bladder cancer, as well as in advanced ovarian and pancreatic cancers directly injected into the tumour.

In a current scenario where endovesical therapies are limited, the proposal of new alternatives could help us to manage non muscle invasive bladder cancer in a better way. Further research is warranted in this field of special interest.