New target immunotoxin! Vicinium initiated rolling submission for the treatment of high-risk BCG unresponsive non muscle invasive bladder cancer (NMIBC)!

December 29, 2019 / Biogen / -- sesen bio is a biopharmaceutical company in the late clinical stage, focusing on the development of targeted fusion protein therapy for cancer Recently, the company announced that it has started rolling submission of biocinium (oportuzumab monatox) biological product license application (BLA) to the U.S Food and Drug Administration (FDA), which is a next generation antibody drug conjugate (ADC) for the treatment of non muscle invasive bladder cancer (NMIBC) that does not respond to BCG In 2018, the FDA awarded vicinium fast track design Rolling reviews allow pharmaceutical companies to submit completed parts of their new drug application (NDA) or biological product licensing application (BLA) to FDA without waiting for each part to be completed before reviewing the entire NDA or bla Currently, sesen bio has submitted completed non clinical and clinical modules, partially completed chemical, manufacturing and control (CMC) modules After the final completion of the CMC module, the company expects to complete the BLA submission in 2020 If FDA accepts bla, the company plans to apply for priority review Dr Thomas Cannell, President and CEO of sesen bio, said: "at present, there are still significant unmet medical needs in NMIBC treatment, which is further complicated by the continuous shortage of BCG vaccine Launching vicinium BLA rolling submission marks a great achievement of sesen bio and an important step forward in helping to save and restore the lives of cancer patients " Bladder cancer is the sixth most common cancer in the United States, about 80% of which is NMIBC, that is, cancer cells are located in the bladder or have grown into the bladder cavity, but have not spread to muscle or other tissues NMIBC mainly affects men and is related to carcinogen exposure The recurrence rate after initial surgical resection is very high, more than 60% of patients will receive BCG immunotherapy Although BCG is effective in many patients, tolerance problems have been observed and many patients experience relapses If BCG is ineffective or patients need to receive BCG for a long time, the recommended treatment is radical cystectomy Vicinium, a locally administered fusion protein, is a leading candidate product of sesen bio and is being developed for the treatment of high-risk NMIBC Vicinium is a human scFv immunotoxin targeting the epithelial cell adhesion molecule (EpCAM) antigen on the surface of tumor cells It is formed by the coupling of recombinant human anti EpCAM antibody scFv and Pseudomonas exotoxin A once combined with EpCAM expressed by cancer cells, it will be internalized into the cytoplasm and induce apoptosis Vicinium is composed of a stable gene engineering peptide chain to ensure that exotoxin A remains attached until internalized by cancer cells, so as to reduce the risk of toxicity to healthy tissues and improve safety Preclinical studies have shown that EpCAM is overexpressed in NMIBC cells, but rarely or not in normal bladder cells In the United States and the European Union, vicinium was granted orphan drug qualification in 2005 and fast track qualification by FDA in August 2018, which was used to treat NMIBC that was not effective for BCG immunotherapy In August this year, sesen bio released the updated primary and secondary endpoint data of Vista (nct02449239), a phase III clinical study of vicinium in the treatment of bladder cancer The updated 12-month data further supports the strong benefits and risks of vicinium in the treatment of high-risk, BCG unresponsive, non muscle invasive bladder cancer (NMIBC) patients These data are also the basis for the company to submit BLA to the US FDA Vista is a single arm, 24-month, open label, multicenter phase III study that is evaluating vicinium as a single drug therapy for high-risk, unresponsive NMIBC patients treated with intravesical administration of BCG immunotherapy A total of 133 patients with advanced NMIBC carcinoma in situ (CIS) or papillary carcinoma (with or without CIS) were enrolled in the study These patients were treated with BCG In the study, patients entered three cohorts (cohort 1: refractory or relapsed CIS within 6 months of BCG treatment; cohort 2: relapsed CIS within 6-11 months of BCG treatment; cohort 3: refractory or relapsed papillary carcinoma [without CIS] within 6 months of BCG treatment) according to the time of disease recurrence after histology and adequate BCG treatment (at least 2 courses of BCG, at least 5 doses in the first course and at least 2 doses in the second course) In the study, patients were treated with vicinium twice a week for six weeks, then once a week for six weeks, and then once every other week for two years By the end of May 29, 2019, the primary and secondary endpoint data were updated as follows: (1) complete remission rates: 39%, 26%, 20%, 17% and 57%, 57%, 43%, 14% at 3, 6, 9, and 12-month time points for queues 1 and 2; 40%, 28%, 21%, 17% at 3, 6, 9, and 12-month time points for queues 1 and 2 (2) Duration of remission: the median time of queue 1 was 273 days; the summary analysis of all CIS patients in queue 1 and queue 2 showed that 52% of the patients who achieved complete remission at the time point of 3 months had the duration of complete remission ≥ 12 months after the start of treatment (3) Relapse time: high risk papillomas NMIBC is associated with higher progression and relapse rate, so relapse time is a key secondary end point for high risk papillomas NMIBC patients, and the median relapse time for cohort 3 patients is 402 days (4) Time of cystectomy: according to FDA guidelines, the goal of non responsive NMIBC therapy is to avoid cystectomy, so the time of cystectomy is a key secondary end point The results show that by using Kaplan Meier method, it is estimated that more than 75% of patients will still remain without cystectomy in 2.5 years, and 88% of respondents will remain without cystectomy in 3 years (5) Progression free survival: Kaplan Meier method was used to analyze the progression free survival of 90% patients ≥ 2 years (6) Event free survival: using Kaplan Meier method, 29% patients maintained event free survival at 12 months (7) Total survival time: using Kaplan Meier method, 96% patients had a total survival time ≥ 2 years (8) Safety: vicinium continued to show good tolerance, 95% of adverse events were level 1 or level 2 The most common treatment-related adverse events were dysuria (14%), hematuria (13%) and urinary tract infection (12%), all of which were consistent with the characteristics of bladder cancer patients and the use of catheters for treatment, and controllable and reversible Source: sesen bio initiates rolling submission of BLA for vicinium to FDA