Clinical Data: A Linear Path to Approval Based on FDA Guidance

Since the introduction of BCG as the standard of care for the adjuvant therapy of NMIBC, there has been minimal progress in the development of new agents for this condition. In 2018, the FDA published guidance for drug development for NMIBC, based largely on cumulative advancements in the understanding of the clinical course of this disease, and on discussions with experts in the field (click here for link). Our early clinical development program has been carried out in accordance with these recommendations. The aim has been to demonstrate that inodiftagene vixteplasmid (BC-819) has objective activity against established bladder cancer as a foundation for designing registrational trials.

We have undertaken three clinical trials to date in bladder cancer. The first, a phase 1/2 dose-escalation trial, and the second, a phase 2 monotherapy study, are complete. The third trial, a phase 2 trial of BC-819 administered as induction therapy with BCG, has completed enrollment and follow-up is ongoing. The major findings of the trials are summarized here:

The FDA is clear in its guidance that it expects the demonstration of activity against active tumors. In our phase 1/2 and phase 2 trials, we employed a marker lesion design. Patients underwent complete resection of all existing tumors except a single marker tumor. After 12 weeks of BC-819 administration the response of the tumor was assessed. Complete responses were observed in 17/57 patients (30%) in the two studies, demonstrating activity against established cancer. These results are shown below:

Left: baseline papillary tumor
Right: 3 weeks following 6th instillation of BC-819: necrosis


After responses, the durability of remission is the most important clinical parameter in patients undergoing adjuvant therapy after resection. In the two monotherapy trials, 12-month recurrence-free rates are 46% (26/57), and 24-month recurrence-free rates 33% (19/57). The results compare favorably with historical 24-month experience for treatment of BCG-unresponsive disease with investigational therapies of approximately 20% (ref. 1). Data from the phase 2 combination study showed recurrence free survival of 68% and 54% at 12 and 24 months.


  1. Jarow et al., J. Urology, 2014