New immunotoxin! Vicinium treatment of high-risk BCG non-response bladder cancer (NMIBC) EU regulatory pathway clear, the United States into rolling review!

May 08, 2020 /
BioValley
BIO/ -- SeenBio is a late-stage, clinical biopharmaceutical company focused on developing targeted fusion protein therapies for cancer Recently, the company announced that it had received positive scientific advice from the European Medicines Agency (EMA) Committee on Human Medicine products (CHMP) on the EU regulatory approach to the new targeted immunotoxin Vicinium (oportuzumab monatox, VB4-845) is a next-generation antibody Flavor drug conjugate (ADC), is a humanized cFv immunotoxin that is targeted at epithelial cell adhesion molecule (EpCAM) antigen spree tumor cell surface, by recombinant humanized anti-Humanized Anti-EpCAM antibody cFv and pseudomonocytical exotoxin A conjugated, once bound to cancer cells to express Epapopite will be linked to
the cell Vicinium developed for the treatment of high-risk, non-muscle-immersed bladder cancer (NMIBC) patients who do not respond to BCG In both the United States and the European Union, Vicinwas was granted orphan drug status in 2005 and FDA in August 2018 to be eligible for fast-track treatment of NMIBC that is ineffective for BCG immunotherapy December 2019, Seen Bio initiated a rolling application for Vicinium's Biological Products Licensing (BLA) to the U.S FDA through a rolling review process The FDA's rolling review mechanism allows pharmaceutical companies to submit completed portions of their new drug applications (NDA) or Biological Products Licensing (BLA) to the FDA without having to wait until each section is complete before reviewing the entire NDA or BLA key elements from CHMP's scientific recommendations: (1) CHMP agrees that the company's non-clinical, clinical pharmacology and safety databases are sufficient to support Vicinium's marketing authorization application (MAA), and THAT CHMP does not require additional clinical trials to support MAA submissions to THE MAA (2) CHMP agree that, given the well-known effects of cystomy on patient morbidity and quality of life, a new topical therapy that can prevent the patient from acurable cysytomy will be very meaningful, especially for those with contraindications (3) CHMP provides guidance on additional data analysis that they hope will be included in the MAA, which Seen Bio believes can be fully resolved with a complete Phase III data set (4) Based on the guidance received, Seen Bio expects to submit Vicinium's MAA to EMA in early 2021 and obtain potential approval in early 2022 (5) the company expects to receive scientific advice from CHMP on the Vicinium Chemical, Manufacturing and Control (CMC) program at a later date Seen Bio believes that Vicinium has a significant business opportunity in Europe and expects peak sales in Europe to be significantly higher than peak sales in the United States due to the region's significantly higher incidence of bladder cancer and strong pricing benchmarks Dr Thoma Cannell, President and CEO of Seen Bio, said: "We are pleased to receive positive guidance from CHMP on the Vicinium regulatory approval approach We firmly believe that Vicinium is a highly differentiated candidate for the large number of unmet needs in NMIBC This encouraging development has increased our confidence in bringing Vicinium to the European market, which is a huge opportunity for the company We will continue to work with the European Medicines Agency to through the approval process as quickly as possible "
bladder cancer is a common type of cancer, about 80% of which is NMIBC, i.e cancer cells are located in the bladder or have grown into the bladder cavity, but have not spread to muscles or other tissues NMIBC mainly affects men and is associated with carcinogen exposure Patients have a high recurrence rate after initial surgical excision treatment, and 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 recurrence of the disease If BCG is not effective or the patient needs to receive BCG for a long time, the recommended treatment is a complete removal of the bladder , a locally prescribed Fusion Protein, is a leading candidate for Seen Bio and is being developed to treat high-risk NMIBC The reproducing cFv immunotoxin, which is a humanized cFv immunotoxin targeted by the epithelial cell adhesion molecule (EpCAM) antigen on the surface of tumor cells, is formed by recombinant humanized anti-EpCAM antibody cFv and pseudo-monocytobacteria exotoxin A, once the EpCAM expressed by the cancer cells is internalized into the cytoplasm, inducing cell apoptosis consists of a stable chain of genetically engineered vicinpeptides to ensure that the topical toxin A remains attached until it is internalized by cancer cells, thereby reducing the risk of toxicity to healthy tissue and improving safety Preclinical studies have shown that EpCAM is overexpressed in NMIBC cells and rarely or not in normal bladder cells In both the United States and the European Union, Vicinwas was granted orphan drug status in 2005 and by the FDA in August 2018 to be eligible for fast-track treatment of NMIBC for BCG immunotherapy The Mechanism of Action In August 2019, Seen Bio published preliminary primary and secondary endpoint data for the updated Phase III clinical study VISTA (NCT02449239) for the treatment of bladder cancer The updated 12-month data further supports the strong benefit risk stoain for Vicinium treatment of patients with high risk, BCG non-responsive, non-muscular leachate bladder cancer (NMIBC), which is the basis for the company's submission of BLA to the
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, BCG immunotherapy-free NMIBC patients without response A total of 133 patients with high-level NMIBC in situ cancer (CIS) or papilloma (accompanying or not accompanied cIS) were in the study group who had been treated with BCG In the study, patients followed histology and adequate BCG treatment (at least 2 courses of BCG, at least 5 doses of the first course of treatment, at least 2 doses of the second course) and the recurrence time of the disease into 3 queues (queue 1: BCG treatment within 6 months difficult to treat or relapse CIS; queue 2: BCG treatment within 6 to 11 months recurrent CIS; queue 3: BCG treatment within 6 months difficult to treat or relapse papilloma (No CIS) In the study, patients received local administration of the drug, the local drug, the vicinium, twice a week for 6 weeks, followed by a weekly treatment for 6 weeks, followed by treatment every other week for 2 years By the end of the data deadline of 29 May 2019, the primary and secondary endpoint data were updated as follows: (1) full mitigation rates : queues 1 and 2 are 39% at 3 months, 6 months, 9 months, 12 months, 2 6%, 20%, 17% and 57%, 57%, 43%, 14%, and queues 1 and 2 aggregates show 40%, 28%, 21%, 17% at 3 months, 6 months, 9 months, 12 months (2) the duration of the remission was : the median time of queue 1 was 273 days, and a summary analysis of all CIS patients in queue 1 and queue 2 showed that 52% of patients who achieved full remission at the 3-month time point had a total remission duration of 12 months (3) the recurrence time of the disease was : high-risk papilloma NMIBC was associated with higher progression and recurrence rate, so the recurrence time was a key secondary endpoint for patients with high-risk papilloma NMIBC, and the median disease recurrence time of patients in queue 3 was 402 days (4) Bladder excision time : FDA guidelines indicate that BCG non-responsive NMIBC treatment goal is to avoid bladder excision, so the cystomy time is a key secondary endpoint, the results show that using the Kaplan-Meier method analysis, estimated that 75% of patients remain bladder untorescarmy for 2.5 years, 88% of respondents remain bladder untoresusd for 3 years (5) no progression survival : using the Kaplan-Meier method, 90% of patients had no progression survival of 2 years (6) event-free survival : using the Kaplan-Meier method, 29% of patients remained event-free at the 12-month point (7) total survival : using the Kaplan-Meier method analysis, 96% of patients total survival period of 2 years (8) safety : vicinium continues to exhibit good tolerance, with 95% of adverse events being Level 1 or 2 The most common treatment-related adverse events were urination difficulty (14%), hematuria (13%) and urinary tract infections (12%), all of which were consistent with the characteristics of patients with bladder cancer and treated with catheters, and were controllable and reversible (BioValleyBioon.com) original source: SeenBio Report Poitive Interaction with EMA on Regulatory Pathway for Vicin