Astellas Pharmaceutical Group (Tokyo Stock Exchange: 4503, President and Chief Executive Officer: Naoki Okamura, "Astellas") announced on August 20 that the Center for Drug Evaluation (CDE) of the China National Drug Administration has approved Vientumab for injection (trade name: Vientumab is indicated for the treatment of locally advanced or metastatic uroepithelial carcinoma (mUC) in adult patients who have previously received platinum-containing chemotherapy and programmed death receptor-1 (PD-1) or programmed death ligand-1 (PD-L1) inhibitors.
Urothelial carcinoma is a serious and common cancer that affects the lower urinary tract (including the bladder and urethra) as well as the upper urinary tract (including the ureters and renal pelvis). In 2022, more than 92,000 patients in China were diagnosed with bladder cancer, of which about 41,000 patients sadly died. Survival rates are particularly poor for patients with advanced or metastatic urothelial cancer, so new treatments are urgently needed to extend patients' lives.
Professor Guo Jun, Director of the Department of Melanoma and Sarcoma and Urologic Oncology, Peking University Cancer Hospital, pointed out: "On August 13, 2024, the National Medical Products Administration (NMPA) officially approved Vientumab for injectable use in adult patients with locally advanced or metastatic uroepithelial carcinoma who have previously received platinum-containing chemotherapy and programmed death receptor-1 (PD-1) or programmed death ligand-1 (PD-L1) inhibitors. The approval is based on a global Phase 3 registration study and a bridging study in the Chinese population. This is a landmark event that marks the accessibility of new antibody-drug conjugate (ADC) therapies for the entire population of UC."
Ahsan Arozullah, MD, MPH, senior vice president and head of oncology area Development at Astellas, said: "We are committed to driving scientific advances that will significantly change the course of cancer care around the world. The approval of Veentumab by the Center for Drug Evaluation (CDE) of the China National Drug Administration provides another treatment option for patients with locally advanced or metastatic urothelial carcinoma in China, and patients are expected to have better treatment outcomes as a result."
Data from the global study EV-301 and its Chinese bridging study EV-203 support CDE's approval of Veentumab. The randomized Phase 3 study EV-301 supports the worldwide registration of Veentumab. The EV-203 study (NCT04995419) is a single-arm, open-label, multicenter phase 2 study in Chinese patients with locally advanced or metastatic uroepithelial carcinoma who have previously been treated with PD-1/PD-L1 inhibitors and platinum-containing chemotherapy. The results showed that EV-203 met its primary endpoint, which was a confirmed objective response rate (ORR) as assessed by an Independent Review Committee (IRC) in patients treated with Veentumab monotherapy compared to historical controls (37.5% [n/N=15/40; 95% confidence interval: 22.7-54.2]) was statistically significant. Efficacy and pharmacokinetic data from the study were consistent with global data, and safety results showed mostly grade 1-2 treatment-related adverse events.
Astellas has already reflected the impact of the approval of Veentumab in China in its financial forecast for fiscal year 2024 (ending March 31, 2025).
About the EV-203 study
The Phase II clinical trial of EV-203 (NCT04995419) is a multicenter, single-arm bridging study conducted in China to evaluate the efficacy, safety, and pharmacokinetics of Veentumab in Chinese patients. The study included a total of 40 patients with locally advanced or metastatic urothelial carcinoma who had previously been treated with platinum-containing chemotherapy and PD-1/PD-L1 inhibitors.
The primary endpoint of the trial was met, and the confirmed objective response rate in patients treated with Veentumab monotherapy was 37.5% as assessed by an independent review board (n/N=15/40, 95% confidence interval [CI] : 22.7-54.2). Of these, 1 patient achieved a complete response (2.5%) and 14 patients achieved a partial response (35%).
No new safety signals were found in the study. The majority of veentumab treatment-related adverse events were grade 1-2, with 2 patients discontinuing treatment due to treatment-related adverse events (acute coronary syndrome and hyperglycemia/rash).
About the EV-301 study
The EV-301 clinical trial (NCT03474107) is a global multicenter, open, randomized Phase III trial designed to evaluate the efficacy of Veentutuzumab compared to chemotherapy (docetaxel, paclitaxel, or vinflunine). Efficacy and safety in the treatment of 608 patients with locally advanced or metastatic urothelial carcinoma who had previously received platinum-containing chemotherapy and PD-1/L1 inhibitors. The primary endpoint was overall survival (OS), and secondary endpoints included progression-free survival (PFS), overall response rate (ORR), duration of response (DOR), and disease control rate (DCR), as well as safety/tolerability and quality of life parameters.
The EV-301 study showed that median overall survival was longer in the veentumab group than in chemotherapy (12.88 and 8.97 months, respectively; Risk ratio: 0.70; 95% confidence interval: 0.56 to 0.89; p=0.001), the progression-free survival was also longer than that in the chemotherapy group (5.55 months vs. 3.71 months, respectively; Hazard ratio: 0.62; 95% confidence interval: 0.51 to 0.75; P<0.001). The incidence of treatment-related adverse events was similar between the two groups (93.9% in the veentumab group and 91.8% in the chemotherapy group). The incidence of grade 3 and above adverse events was also similar in both groups (51.4% and 49.8%, respectively). The results were published in the New England Journal of Medicine.
About bladder cancer and urothelial cancer
Urothelial cancer, or bladder cancer, originates in urothelial cells, which are found in the urethra, bladder, ureter, renal pelvis, and some other organs. Urothelial carcinoma accounts for 90% of all bladder cancer cases and may also occur in the renal pelvis, ureter and urethra. If bladder cancer has spread to surrounding organs or muscles, it is called locally advanced disease. If the tumor has spread to other parts of the body, it is called metastatic disease. About 12% of cases have locally advanced or metastatic urothelial carcinoma at diagnosis.
In China, the incidence of bladder cancer ranked 11th among all cancers in 2022, with more than 92,000 new cases estimated that year. The five-year prevalence of bladder cancer in China is estimated at 2.5 per 100,000 cases, or 276,102 cases. Continuous treatment and monitoring make bladder cancer one of the most expensive cancers to treat, with the highest costs compared to other malignancies.
About Bexoft (generic name Vientumab for injection)
Veentumab is a first-of-its-kind antibody-drug conjugate (ADC) that targets the Nectin-4 protein, which is expressed on the cell surface and is highly expressed in bladder cancer. Non-clinical studies have shown that by binding to cells expressing the Nectin-4 protein, the anti-tumor component monomethyloratatin E (MMAE) is internalized and released into cells, causing cell proliferation arrest (cell cycle arrest) and programmed cell death (apoptosis), thereby exerting its anticancer activity.
Ongoing research
The EV-302 clinical trial (NCT04223856) is an open-label, randomized, controlled Phase 3 clinical trial designed to evaluate the combination of veentutuzumab and pabolizumab compared to platinum-containing chemotherapy. Efficacy in patients with untreated locally advanced or metastatic urothelial carcinoma (la/mUC) suitable for cisplatin or carboplatin therapy is not limited by PD-L1 expression.
The EV-103 clinical trial (NCT03288545) is an ongoing multi-cohort, open-label, multi-center phase 1b/2 clinical trial. To investigate the efficacy of veentuzumab alone or in combination with pabolizumab and/or chemotherapy in the treatment of first - or second-line locally advanced or metastatic urothelial carcinoma and in patients with myoinvasive bladder cancer (MIBC).
The EV-104 trial (NCT05014139) is a Phase 1 study designed to explore the feasibility of using Veentumab in patients with non-myoinvasive bladder cancer (NMIBC). The study was divided into two parts, evaluating dose escalation and dose extension of veentumab as postoperative monotherapy.
Studies of the combination of Vientumab and pabolizumab in different stages of uroepithelial cancer, including two Phase 3 trials EV-304 (NCT04700124, also known as the KEYNOTE-B15 trial) and EV-303 (NCT03924895, also known as the KEYNOTE-905 trial), Both were targeted at muscular invasive bladder cancer.
The EV-202 trial (NCT04225117) is an ongoing, multi-cohort, open-label, multicenter phase 2 clinical trial investigating the efficacy of Veentumab alone in previously treated patients with advanced solid tumors. The trial also included a cohort studying the combination of veentuzumab and pabolizumab in previously untreated relapsed and metastatic head and neck squamous cell carcinoma.
About Astellas
Astellas Pharmaceutical Group is a global pharmaceutical company with operations in more than 70 countries and regions. The company is pursuing a "Focus Area Approach" to address unmet medical needs by focusing on physiological mechanisms and treatments to identify opportunities for continued development of new drugs. At the same time, the company is looking beyond prescription drugs to create Rx+® medical solutions by combining expertise and knowledge with cutting-edge technology from external partners in different fields. Through these efforts, Astellas is committed to being at the forefront of the ever-changing healthcare industry, translating scientific advances into value for patients. More detailed information, please visit the website https://www.astellas.com/en.
About Astellas' partnership with Pfizer
Astellas and Pfizer jointly develop and commercialize Veentumab on a 50:50 basis worldwide. In the United States, Astellas and Pfizer jointly promote PADCEV® (enfortumab vedotin-ejfv). Pfizer is responsible for the commercialization and registration of the product in the Americas (excluding the United States). Astellas is responsible for the commercialization and registration of the product outside the Americas.