dm+d

Unassigned

New Medicines

ViciniumNon-muscle invasive bladder cancer (NMIBC) specifically CIS and/or high-grade Ta or T1 disease, who had previously failed bacillus Calmette-Guérin (BCG) treatment, with or without interferon

Information

Vicinium
New molecular entity
Sesen Bio
Sesen Bio

Development and Regulatory status

None
Filing withdrawn
Not recommended for approval (Negative opinion)
May 22Following meetings with regulators Sensen Bio preps for a new PIII trial [14].
Nov 21Sesen Bio plans to conduct an additional clinical trial for potential resubmission of filings. It expects to hold a Type C meeting with the US FDA to discuss the clinical trial protocol in early 2022 [13].
Aug 21Sensen has withdrawn filing for Vicineum in Europe. The company have paused plans to seek approval in the EU until it has more clarity on the next steps in the US [12].
Aug 21FDA issues a Complete Response Letter to Sesen Bio, stating it cannot approve the BLA for Vicineum in its present form, and recommending additional clinical and statistical data analyses, as well as issues related to the company´s Chemistry, Manufacturing and Controls (CMC) [11].
Mar 21Sesen Bio has submitted its Marketing Authorization Application to the EMA for Vicineum for the treatment of high-risk BCG-unresponsive non-muscle invasive bladder cancer [10].
Dec 20Sesen Bio announces submission of the completed BLA to the US FDA. The BLA is supported by the data from the pivotal PIII VISTA trial. Sesen Bio has also requested for an Priority Review (six-month target PDUFA date) under its existing Fast Track Designation, and expects the decision in early 2021 [8].
Oct 20Sesen Bio successfully completes a pre-submission meeting with the EMA for oportuzumab monatox in Europe for the treatment of patients with high-risk, BCG unresponsive NMIBC. During the meeting, the EMA addressed product-specific, legal, regulatory and scientific topics related to oportuzumab monatox. This successful pre-submission meeting with the EMA follows written notice from the EMA that oportuzumab monatox has received confirmation of eligibility to file an MAA under the agency’s centralised procedure. Confirmation of eligibility was given in response to the submission of a letter of intent, which notified the EMA that the company intended to file an MAA. In addition, EMA reaffirms the company’s intent to complete all necessary pre-submission activities with the EMA by the end of 2020 [8].
Dec 19Sesen have initiated the submission of its Biologics License Application for Vicinium for the treatment of BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) under Rolling Review to the U.S. Food and Drug Administration (FDA) [7].
Aug 18FDA grant Vicinium Fast Track Designation for treatment of BCG-unresponsive high-grade NMIBC [5].
May 18PIII VISTA trial ongoing with an estimated primary completion date of Dec 18. [2-4]

Category

Oportuzumab monatox binds specifically to EpCAM receptors expressed on bladder cancer cells where it delivers cytotoxic Pseudomonas Exotoxin A (ETA), disrupting protein synthesis and leading to cell death.[2,3]
Bladder cancer is the 7th most common cancer in the UK and it is the cause over more than 5,000 deaths in the UK each year. The overall incidence in the UK is 11.4 per 100,000 population. The majority of cases occur in patients aged over 60 years. Men outnumber women by 3:1 but women tend to have a poorer prognosis.[1]
Non-muscle invasive bladder cancer (NMIBC) specifically CIS and/or high-grade Ta or T1 disease, who had previously failed bacillus Calmette-Guérin (BCG) treatment, with or without interferon
Intravesical

Trial or other data

Oct 20PIII VISTA, no longer recruiting, is due to complete collection of primary outcome data in Dec 20 [9].
May 20Three-months data from the PIII VISTA trial of oportuzumab monatox in 133 patients with high-grade NMIBC, which is either carcinoma in situ (CIS) or papillary with or without CIS demonstrated a complete response rate (CRR) of 40% in the first cohort (n=89) and the median duration of response was 9.4 months (95% CI, 5.1-NE). Of the 3-month CIS responders, 52% remained disease-free for 12 months after starting treatment. The recurrence-free rates of the evaluable papillary patients (n=38) at 3, 6, 12 and 24 months were 71, 58, 50 and 37%, respectively, and the median time to recurrence was 13.2 months (95% CI, 5.6-NE). Overall, responders at 3 months remained radical cystectomy (RC)-free for 34.0 vs. 20.7 months for non-responders (p ≤ 0.001). Moreover, the rate of RC was only 10% (6 of 63) for the 3-month responders versus 32% (18 of 56) for the non-responders. Preliminary overall survival was 96% (95% CI, 92-100) at 2 years [8].
Jan 19PIII VISTA trial primary outcome data finds clinically meaningful complete response rates in evaluable Carcinoma in situ patients at three, six, nine and 12 months of follow-up in the trial [6].
May 18Positive, 3-month data from ongoing PIII VISTA Trial of Vicinium™ for the treatment of pts with high-grade NMIBC who have been previously treated with BCG. The efficacy data being reported are based on 3-month follow-ups from 111 pts with high-grade NMIBC that is either carcinoma in situ (CIS). In cohort 1, 72 pts were evaluable for 3-month data and Vicinium demonstrated a complete response rate of 39%. In evaluable pts in cohort 2 (n=5), treatment with Vicinium demonstrated a complete response rate of 80%. In an analysis assessing pooled CIS patients from cohorts 1 and 2 (n=77), Vicinium treatment resulted in a complete response rate of 42% at 3 months. In cohort 3´s evaluable pts (n=34), treatment with Vicinium demonstrated a 68% recurrence-free rate at 3 months. To date, Vicinium has been well-tolerated in the VISTA Trial and 72% of all adverse events were Grade 1 or 2 (UTI, dysuria, haematuria, pollakiuria, diarrhoea , fatigue, micronutrition urgency, nausea and increased lipase). Only 4% were Grade 3 or 4 with no Grade 5 adverse events; serious adverse events including acute kidney injury or renal failure and cholestatic hepatitis. Twelve-month data are expected by mid-2019.[3]
Mar 18Enrolment in the non-randomised, open label, PIII VISTA trial (n=133 pts in US or Canada) completed in pts with non-muscle invasive bladder cancer (NMIBC) (VB4-845-02-IIIA; NCT02449239). The trial assessed the complete response rate of 30mg intravesicular oportuzumab monatox in pts with NMIBC, specifically CIS and/or high-grade Ta or T1 disease, who had failed BCG treatment +/-interferon. Pts in the trial are to receive locally administered Vicinium twice a week for 6 weeks, followed by once-weekly treatment for another 6 weeks, then treatment every other week for up to 2 years. The defined primary endpoint is the complete response rate. The clinical trial includes three patient cohorts based on histology and time to recurrence after adequate BCG: Cohort 1 (n=87): pts with CIS with or without papillary disease whose cancer recurred within 6 months of their last course of BCG treatment. Cohort 2 (n=6): pts with CIS with or without papillary disease whose cancer recurred after 6 months, but before 11 months, after their last course of BCG treatment. Cohort 3 (n=40): pts with papillary disease without CIS whose cancer recurred within 6 months of their last course of BCG treatment. [2,3]
Jan 09PII trial of VB4845 in 46 pts with locally recurrent, non-invasive Cis (carcinoma in situ) bladder cancer (VB4-845-02-IIA; NCT00462488). Pts were administered VB4 845 (Vicinium™) weekly using intravesical instillation over 6 weeks. After the 6-week induction phase, pts responsive to therapy received up to 3 additional maintenance cycles over a total treatment period of 51 weeks. Data from the trial demonstrated complete response and favourable safety in the treated pts. The interim analysis showed no evidence of disease in 4/12 pts at week 12 and 2/5 pts at week 25. The overall response rate was 95%, where 42% of patients had a complete response, 13% had a partial response, and 40% had stable disease.[2]