Qilu Pharma Inks $35M Deal with Sesen Bio to Bring Bladder Cancer Therapy Vicineum to Greater China

August 02, 2020 /Bio ValleyBIOON/ -- Qilu Pharmaceutical and U.S.-based Sesen Bio recently entered into an exclusive licensing agreement, granting Qilu Pharmaceutical the exclusive rights to develop and commercialize Sesen Bio’s investigational new drug Vicineum (oportuzumab monatox, VB4-845) in the Greater China region (Mainland China, Hong Kong, Macau, and Taiwan). Vicineum is being developed for the treatment of Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) as well as other types of cancer. The total value of this collaboration transaction amounts to USD 35 million.For details on the collaboration and the Vicineum project, please refer to: July 2020 Business Update Presentation）

Under the terms of the agreement, Sesen Bio grants Qilu Pharmaceutical an exclusive license to develop and commercialize Vicineum in the Greater China region. Sesen Bio will receive a $12 million upfront payment and is eligible for $23 million in technology transfer and regulatory milestone payments. Upon commercialization of Vicineum in the Greater China region, Sesen Bio is also entitled to royalties based on net sales in the Greater China region.

Sesen Bio will retain full development and commercialization rights for Vicineum in the treatment of NMIBC in the United States and all other regions worldwide, excluding Greater China. The terms of the agreement also include the transfer of Vicineum’s manufacturing technology to Qilu Pharmaceutical. Qilu Pharmaceutical’s world-class manufacturing expertise represents an opportunity to scale up production in the future to meet the anticipated substantial global demand for Vicineum in the treatment of NMIBC.

Vicineum isNext-Generation Antibody-Drug Conjugates (ADCs), a fusion protein for local administration, is based onTumorA humanized scFv immunotoxin targeting the epithelial cell adhesion molecule (EpCAM) antigen on the cell surface, composed of a recombinant humanized anti-EpCAM antibody scFv conjugated with Pseudomonas exotoxin A. Upon binding to EpCAM expressed on cancer cells, it is internalized into the cytoplasm, inducingApoptosis。

Vicineum consists of a stable genetically engineered peptide chain to ensure that exotoxin A remains attached until it is internalized by cancer cells, thereby reducing the risk of toxicity to healthy tissues and improving safety. Preclinical studies have confirmed that EpCAM is overexpressed in NMIBC cells but barely expressed in normal bladder cells. Vicineum was granted orphan drug status in both the United States and the European Union in 2005, and in August 2018, it wasFDAGranted Fast Track designation for the treatment of BCG-unresponsive NMIBC.

Bladder cancer is a common malignancy, with approximately 80% of cases classified as non-muscle-invasive bladder cancer (NMIBC), meaning the cancer cells are confined to the inner lining of the bladder or have grown into the bladder lumen but have not yet invaded the muscle layer or other tissues. NMIBC predominantly affects males and is associated with exposure to carcinogens. The recurrence rate after initial surgical resection is high, with over 60% of patients undergoing Bacillus Calmette-Guérin (BCG) immunotherapy. Although BCG is effective in many patients, issues with tolerance have been observed, and many patients experience disease recurrence. If BCG therapy fails or if long-term BCG treatment is required, radical cystectomy is the recommended therapeutic approach.

In December 2019, Sesen Bio initiated the rolling submission of its Biologics License Application (BLA) for Vicinium to the U.S. FDA through the rolling review process. The FDA’s rolling review mechanism allows pharmaceutical companies to submit completed sections of their New Drug Application (NDA) or Biologics License Application (BLA) to theFDA, without having to wait until each section is completed before reviewing the entire NDA or BLA. In May 2020, Sesen Bio received positive scientific advice from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) regarding the EU regulatory pathway for Vicineum.

The efficacy of Vicinium in treating BCG-unresponsive non-muscle-invasive bladder cancer (NMIBC) has been confirmed in the Phase III VISTA study (NCT02449239). In August 2019, Sesen Bio announced the data for the primary and secondary endpoints of this study. The updated 12-month data further supported the strong benefit-risk profile of Vicinium in patients with high-risk BCG-unresponsive NMIBC, which also formed part of the company’s submission to the U.S.FDAThe basis for submitting a BLA.

Bladder Cancer - (Image source: medscape.com)

VISTA is a single-arm, 24-month, open-label, multicenter Phase III study evaluating vicinium as a monotherapy administered via intravesical instillation for the treatment of patients with high-risk, BCG-unresponsive non-muscle-invasive bladder cancer (NMIBC). The study enrolled a total of 133 patients with high-grade NMIBC, including carcinoma in situ (CIS) or papillary carcinoma (with or without CIS), who had previously received BCG therapy. Patients were stratified into three cohorts based on histology and time to disease recurrence following adequate BCG therapy (defined as at least two courses of BCG, with the first course comprising at least five doses and the second course at least two doses): Cohort 1 included patients with refractory or recurrent CIS within 6 months of BCG therapy; Cohort 2 included patients with recurrent CIS occurring 6–11 months after BCG therapy; and Cohort 3 included patients with refractory or recurrent papillary carcinoma (without CIS) within 6 months of BCG therapy. In the study, patients received locally administered vicinium twice weekly for 6 weeks, followed by once weekly for 6 weeks, and then every other week for 2 years.

As of the data cutoff date of May 29, 2019, the primary and secondary endpoint data were updated as follows: (1)Complete Response Rate:The rates for Cohort 1 and Cohort 2 at 3, 6, 9, and 12 months were 39%, 26%, 20%, and 17%, and 57%, 57%, 43%, and 14%, respectively; the pooled data for Cohort 1 and Cohort 2 showed rates of 40%, 28%, 21%, and 17% at 3, 6, 9, and 12 months, respectively. (2)Duration of Response:The median time for Cohort 1 was 273 days; a pooled analysis of all CIS patients in Cohorts 1 and 2 showed that among patients who achieved complete remission at the 3-month time point, 52% maintained complete remission for ≥12 months after treatment initiation. (3)Time to Disease Recurrence:High-risk papillary NMIBC is associated with higher rates of progression and recurrence; therefore, time to disease recurrence is a key secondary endpoint for patients with high-risk papillary NMIBC. The median time to disease recurrence in patients in Cohort 3 was 402 days. (4)Time of Cystectomy:FDAThe guidelines state that the treatment goal for BCG-unresponsive NMIBC is to avoid cystectomy; therefore, time to cystectomy is a key secondary endpoint. The results, analyzed using the Kaplan-Meier method, estimated that >75% of patients remained cystectomy-free at 2.5 years, and 88% of responders remained cystectomy-free at 3 years. (5)Progression-Free Survival:Kaplan-Meier analysis showed that the progression-free survival was ≥2 years in 90% of patients. (6)Event-Free Survival:Kaplan-Meier analysis showed that 29% of patients remained event-free at 12 months. (7)Overall Survival:Kaplan-Meier analysis showed that the overall survival was ≥2 years in 96% of patients. (8)Safety:Vicinium continued to demonstrate favorable tolerability, with 95% of adverse events being Grade 1 or 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 catheter-based treatment, and were manageable and reversible. (Bioon.com)

Original Source: Qilu Pharmaceutical, Sesen Bio