FDA Talks Lead to Voluntary Pause on Development of Vicineum for NMIBC

The development of vicineum for the treatment of patients with high-risk, Bacillus Calmette-Guerin-unresponsive non–muscle invasive bladder cancer has been voluntarily paused.

A voluntary pause has been placed on the development of vicineum for the treatment of patients with high-risk, Bacillus Calmette-Guerin (BCG)-unresponsive non–muscle invasive bladder cancer (NMIBC), according to a press release by Sesen Bio.1

Vicineum is a locally administered, recombinant fusion protein which works to block protein synthesis to mediate tumor cell death. It is currently being investigated across several solid tumor types.

The basis of the decision comes from thorough reassessment of vicineum, including the incremental development timeline and associated costs for an additional phase 3 clinical trial, following recent discussions with the FDA.

"We have had 4 productive meetings with the FDA since August 2021 and we believe we have a full understanding of the FDA’s evolving position and guidance on the following variables: accelerated versus standard approval, single-arm vs randomized controlled trials, comparative versus non-comparative efficacy end points, and adequate versus less-than-adequate BCG patient populations," said Thomas Cannell, MD, president and chief executive officer of Sesen Bio, in the press release. "We have also recently observed an evolution of the current treatment paradigm in NMIBC, with substantial uptake of intravesical chemotherapy (monotherapy and combination therapy) during the ongoing BCG shortage. In assessing the impact of the regulatory and commercial landscape, we have made the decision to pause the clinical development of vicineum."

Previously, a phase 3 study (NCT02449239) of vicineum was completed. The trial included 134 patients with histologically-confirmed non-muscle-invasive urothelial carcinoma of the bladder, those who had refractory disease after adequate BCG treatment, adequate organ function, and who had received adequate BCG treatment.2

In the single-arm study, patients received 30 mg of vicineum in 50 ml of saline, twice a week for a total of 6 weeks followed by the administration of vicineum once a week for 6 weeks. Following the 12-week induction period, patients were administered maintenance vicineum in 50 ml of saline administered once weekly every other week up to 104 weeks.

The primary end point of the study was complete response rate up to 24 months with secondary end points including recurrence rate, event-free survival, number of patients with adverse events (AEs) as a measure of tolerability, changes in echocardiogram, changes in vital signs from baseline, changes in laboratory or physical examination, complete response rate, time to cystectomy, time to disease recurrence, time to progression, progression-free survival (PFS), and overall survival (OS).

Findings revealed that at 3 months, the complete response rate of the evaluable carcinoma in situ (CIS) patients (n = 89) was 40%. The median DoR was 9.4 months (95% CI, 5.1-not evaluable [NE]). Of the patients who responded, 52% remained disease-free for 12 months following the start of treatment. Further, the overall survival rate at 2 years was 96% (95% CI, 92%-100%).

In regard to safety, the majority of the observed AEs were grades 1 and 2, and severe AEs included grade 4 cholestatic hepatitis, grade 5 renal failure, grade 3 acute kidney injury, and grade 2 pyrexia. Only 3% of patients discontinued treatment due to AEs.

Previously, Sesen Bio completed the follow-up stage of a phase 3 clinical trial in the US for the treatment of BCG-unresponsive NMIBC. In February 2021, the FDA accepted a biologics license application (BLA) for vicineum as treatment of BCG-unresponsive NMIBC, granted priority review for the BLA and also set a Prescription Drug User Fee Act (PDUFA) date of August 18, 2021.

The Company also received a complete response letter from the FDA regarding its BLA for vicineum on August 13, 2021 and rejected the request for approval of vicineum as treatment for patients with NMIBC.

With the pause, Sesen Bio continues to assess potential alternatives and intends to seek a partner to aid in further development of vicineum. The activity of vicineum in BCG-unresponsive NMIBC is also being explored at the United States National Cancer Institute in combination with the immune checkpoint inhibitor, durvalumab (Imfinzi).

"We continue to believe that vicineum has benefits for patients and healthcare providers that can be maximized through a company with larger infrastructure, and as such, we intend to find a partner that can execute further development to realize the full potential of vicineum. We now turn our primary focus to the careful assessment of strategic alternatives, which we hope to have completed by the end of the year," added Cannell, in the press release.

References:
  1. Sesen bio announces strategic decision to pause clinical development of vicineum™ in the US. News release. Sesen Bio. July 18, 2022. Accessed July 18, 2022. https://yhoo.it/3Pi1za2
  2. Shore N, O’Donnell M, Keane T, et al. PD03-02 Phase 3 results of Vicinium in bcg-unresponsive non-muscle invasive bladder cancer. J Urol. 2020; 203(suppl 4). doi: 10.1097/JU.0000000000000823.02