BLA for Vicineum in High-Risk, BCG-Unresponsive NMIBC Remains on Track for Regulatory Decision


A Late-Cycle Meeting was held to discuss the biologics license application for Vicineum as a potential option for patients with Bacillus Calmette-Guérin–unresponsive non-muscle invasive bladder cancer.

Bladder Cancer

The late-stage clinical company Sesen Bio recently participated in a Late-Cycle Meeting with the FDA to discuss the biologics license application (BLA) for Vicineum as a potential option for patients with Bacillus Calmette-Guérin (BCG)–unresponsive non–muscle invasive bladder cancer (NMIBC) for which the agent is anticipated to decide on by August 18, 2021.1

During the meeting, both parties discussed remaining questions pertaining to inspection of manufacturing facilities, product quality information requests, and additional information on the chemistry, manufacturing, and controls. They agreed upon a timeline for submission of any supporting information.

No Discipline Review letters have been administered, and the regulatory agency confirmed that no Advisory Committee meeting is planned at this time. Moreover, to date, no issues associated with risk management have been raised. Although both parties discussed required clinical trial and manufacturing post-marketing commitments, the agency did not determine any post-marketing requirements to be necessary at this time.

The FDA will continue to review the BLA, which is on track for a decision by the target Prescription Drug User Fee Act date.

“We are very pleased with the outcome of the Late-Cycle Meeting and continue to feel encouraged by the level of engagement from the FDA in our ongoing discussions regarding the BLA for Vicineum,” Thomas Cannell, DVM, president and chief executive officer of Sesen Bio, stated in a press release. “We understand the FDA’s position on the remaining review items and anticipate a successful resolution of these matters prior to the target PDUFA date. We remain focused on the patient and bringing a differentiated product to market that has the potential to improve patient outcomes while reducing overall healthcare costs.”

Vicineum is a recombinant fusion protein that was developed to target epithelial cell adhesion molecule–specific antigens on the surface of tumor cells to deliver Pseudomonas Exotoxin A, which is a strong inhibitor of protein synthesis.

The product is being explored as a treatment for patients with NMIBC who had previously received BCG, the current standard of care, as part of the open-label, multicenter, single-arm, phase 3 VISTA trial(NCT024492339).2

The trial enrolled patients with disease that was refractory or relapsed following BCG treatment. Patients needed to have a Karnofsky performance status of 60 or higher and acceptable organ function.3 Patients who were pregnant or breastfeeding, had evidence of urethral tract transitional cell carcinoma within the 2 years before treatment, had hydronephrosis, received any intravesicular or other chemotherapy treatment within 2 weeks or an investigational agent 4 weeks before the initial dose of the study drug, were excluded.

The primary efficacy end points of the trial comprised complete response (CR) rate and duration of response (DOR) for patients in cohort 1, and secondary end points included time to disease recurrence for those in cohort 3, and time to cystectomy, progression-free survival, event-free survival, and overall survival (OS) for patients across all cohorts.

Among 89 patients with carcinoma in situ, with or without papillary disease that was refractory or recurred less than 11 months after their last course of BCG, Vicineum was found to elicit a CR rate of 40% (95% CI, 33%-51%) at 3 months. At 6 months, 9 months, and 12 months, the CR rates achieved with the product were 28% (95% CI, 19%-39%), 21% (95% CI, 13%-31%), and 17% (95% CI, 10%-26%), respectively.

Cohort 1 was comprised of patients who had carcinoma in situ with or without papillary disease that was refractory or recurred within 6 months of their last course of BCG (n = 82), and these patients experienced CR rates of 39%, 26%, 20%, and 17% with Vicineum at 3 months, 6 months, 9 months, and 12 months, respectively.

Cohort 2 included those with carcinoma in situ with or without papillary disease that was refractory or recurred after 6 months, but less than or equal to 11 months, after their last course of BCG. At 3 months, the CR rate with the agent was 57% in this subgroup; at 6 months, 9 months, and 12 months, these rates were 57%, 43%, and 14%, respectively.

Patients in cohort 1 experienced a median DOR of 273 days (95% CI, 122–not applicable [NA]) per the Kaplan-Meier method. Additional information collected from an ad-hoc analysis of pooled data for 93 patients in either cohort 1 or 2 demonstrated that among those who responded to Vicineum at 3 months, 52% experienced a CR for 12 months or longer after treatment initiation.

Additional insights from the trial indicated that patients with high-risk papillary disease experienced higher rates of disease progression and recurrence, and the median time to recurrence in 40 patients included in cohort 3 was 402 days (95% CI, 170–NA).

Of all patients who received the product (n = 133) over 75% of patients were estimated to continue to be cystectomy free at 2.5 years. Eighty-eight percent of responders were estimated to remain cystectomy free at 3 years, according to data from an ad-hoc analysis that looked at responders vs non-responders on the trial. Additionally, 90% of all patients given Vicineum are estimated to be progression free at 2 years or longer, and 29% were estimated to remain event free at 1 year. Lastly, 96% of patients were estimated to experience an OS of 2 years or longer.

The majority of adverse effects (AE) reported by patients across the cohorts analyzed on the trial were low grade. The toxicities that were most reported included dysuria (14%), hematuria (13%), and urinary tract infection (12%). AEs were noted to be manageable and reversible.

Toxicity resulted in only 4 patients discontinuing treatment with Vicineum. Fourteen percent of patients reported serious AEs (SAEs), irrespective of treatment attribution. Specifically, 4 SAEs occurred in 3 patients, and they were grade 3 acute kidney injury, grade 2 pyrexia, grade 4 cholestatic hepatitis, and grade 5 renal failure.


  1. Sesen Bio announces productive Late-Cycle Meeting with the FDA for Vicineum. News release. Sesen Bio. July 14, 2021. Accessed July 16, 2021.
  2. Sesen Bio reports positive, preliminary data update from phase 3 VISTA trial for high-risk non-muscle invasive bladder cancer. News release. Sensen Bio. August 8, 2019. Accessed July 16, 2021.
  3. Vicinium treatment for subjects with non-muscle invasive bladder cancer previously treated with BCG. Updated October 14, 2020. Accessed July 16, 2021.
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