FDA Grants Priority Review to Vicineum for High-Risk, BCG-Unresponsive NMIBC


February 17, 2021 - The FDA has accepted and granted a priority review designation to the biologics license application for Vicineum for use in patients with high-risk Bacillus Calmette-Guérin–unresponsive non–muscle invasive bladder cancer.



The FDA has accepted and granted a priority review designation to the biologics license application for Vicineum for use in patients with high-risk Bacillus Calmette-Guérin (BCG)–unresponsive non–muscle invasive bladder cancer (NMIBC), according to an announcement from Sesen Bio, the developer of the drug.1

The regulatory agency will review the application for Vicineum within 6 months, compared with the standard 10 months from the date of the filing. The FDA is not planning to hold an advisory committee meeting to discuss the application; the agency is slated to make its final decision on Vicineum on, or before, August 18, 2021.

“We have been meeting with the FDA regularly for the past 2 years on the application for Vicineum. We understand the FDA’s position and guidance very clearly and have found the review process to be collaborative and engaging,” Thomas Cannell, DVM, president and chief executive officer of Sesen Bio, stated in a press release. “With these critical FDA decisions, we have reached an inflection point for the Company. In addition to a clear regulatory path forward, we have continued to strengthen our balance sheet in preparation for the potential launch of a product we believe represents a significant advancement over available therapies.”

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

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

Results showed that among 89 patients with carcinoma in situ with or without papillary disease that was determined to be refractory or recurred less than 11 months following their last course of BCG, the complete response (CR) rate achieved with Vicineum was 40% (95% CI, 330%-51%) at 3 months. At 6 months, the rate was 28% (95% CI, 19%-39%), whereas it was 21% (95% CI, 13%-31%) and 17% (95% CI, 10%-26%) at 9 months and 12 months, respectively.

Although BCG is an effective option for many patients, tolerability and disease recurrence continue to pose a challenge. If the option does not demonstrate efficacy or the patient can no longer receive it, they are recommended to undergo radical cystectomy. Thus, new options are needed for this population.

The trial completed registration in 2018, with 133 patients enrolled across 3 cohorts based on histology and time to disease recurrence following at least 2 courses of BCG with at least 5 doses in the first course and 2 doses in the second course.

To be eligible for enrollment, patients had to have disease that is refractory or has relapsed after BCG treatment, they had to have a Karnofsky performance status of 60 or greater, and acceptable organ function.3 If patients were pregnant or breastfeeding, had evidence of urethral or upper tract transitional cell carcinoma within the past 2 years, had hydronephrosis, received any intravesicular or other chemotherapy treatment within 2 weeks or an investigational 4 weeks before initial dose of the study treatment, they were excluded.

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

As of the May 29, 2019 data cutoff, the 82 patients with carcinoma in situ with or without papillary disease that was determined to be refractory or recurred within 6 months of their last course of BCG who comprised cohort 1 experienced CR rates of 39%, 26%, 20%, and 17%, at 3 months, 6 months, 9 months, and 12 months, respectively.

Cohort 2 comprised patients with carcinoma in situ with or without papillary disease that was determined to be refractory or recurred after 6 months, but less than or equal to 11 months, following their last course of BCG. Here, the CR rate at 3 months and 6 months was 57%; it was 43% at 9 months and 14% at 12 months.

The median DOR for patients enrolled to cohort 1 was 273 days (95% CI, 122–not applicable [NA]) per the Kaplan–Meier method. Moreover, additional data from an ad-hoc analysis of pooled data for 93 patients in cohorts 1 and 2 showed that among those who experienced a response to treatment at 3 months, 52% achieved a complete response for 12 months or longer following the start of treatment.

High-risk papillary disease was linked with higher rates of progression and recurrence. The median time to disease recurrence in the 40 patients included in cohort 33 was 402 days (95% CI, 170-NA).

Additionally, of all 133 patients who received Vicineum, more than 75% were estimated to continue to be cystectomy free at 2.5 years. Ad-hoc analysis of responders and non-responders for all patient indicated that about 88% of those who responded to treatment were estimated to remain cystectomy free at 3 years.

Ninety percent of all 133 patients who received the agent were estimated to continue to be free of disease progression at 2 years or longer, and 29% of all patients were estimated to remain event free at 12 months. Also, 96% of all patients were estimated to have an OS of 2 years or longer.

Regarding safety, 95% of toxicities experienced by patients across treatment cohorts were grade 1 or 2 in severity. The most frequently reported adverse effects (AEs) associated with treatment included dysuria (14%), hematuria (13%), and urinary tract infection (12%). Toxicities were determined to be manageable and reversible. Only 3% (n = 4) of patients discontinued treatment with Vicineum because of toxicity. Fourteen percent of patients experienced serious AEs (SAEs), irrespective of treatment attribution. Four treatment-associated SAEs were observed in 3 patients and included grade 33 acute kidney injury, grade 2 pyrexia, grade 4 cholestatic hepatitis, and grade 5 renal failure.


  1. Sesen Bio announces FDA acceptance and priority review of its biologics license application for Vicineum. News release. Sesen Bio. February 17, 2021. Accessed February 17, 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 February 17, 2021.
  3. Vicinium treatment for subjects with non-muscle invasive bladder cancer previously treated with BCG. Updated October 14, 2020. Accessed February 17, 2021.
Related Videos
Karl Semaan, MD, MSc
Bradley McGregor, MD, discusses findings from a phase 1b study of abemaciclib  in clear cell renal cell carcinoma.
Toni K. Choueiri, MD
Neil J. Shah, MBBS
Sumanta Kumar Pal, MD, FASCO, chair, Kidney and Bladder Cancer Disease Team; co-director, Kidney Cancer Program; professor, vice chair, Academic Affairs, Department of Medical Oncology & Therapeutics Research, City of Hope
Vivek Subbiah, MD
Marijo Bilusic, MD, PhD
Joshua Linscott, MD
Petros Grivas, MD, PhD
Rohan Garje, MD