—Key trials found that compared with platinum-containing chemotherapy, combination therapy with enfortumab vedotin and pembrolizumab significantly prolonged overall survival and progression-free survival—
—If approved, enfortumab vedotin and pembrolizumab will replace current first-line standard chemotherapy for locally advanced or metastatic urothelial cancer, making it the first combination treatment plan to replace chemotherapy in China—
TOKYO, March 28, 2024/PRNewswire/ -- Astellas Pharmaceuticals Group (TSE: 4503, President and CEO: Naoki Okamura, “Astellas”) announced today that the China National Drug Administration (NMPA) Drug Evaluation Center (CDE) has accepted enfortumab vedotin in combination with pembrolizumab (pembrolizumab) for first-line treatment of previously untreated adult patients with locally advanced or metastatic urothelial carcinoma (LA/MUC) Supplemental Biologics License Application (SBLA). If approved, the combination of enfortumab vedotin and pembrolizumab may change the current treatment model and become the first combination therapy to replace platinum-containing chemotherapy, which is currently the first-line standard treatment for LA/Muc.
Urothelial carcinoma (UC) includes cancer of the lower urinary tract (bladder and urethra) and upper urinary tract (ureter and pelvis), with lower urinary tract cancer accounting for 90% to 95% of all urothelial cancer cases.[i], [ii]There are about 614,000 new cases of bladder cancer worldwide every year, and about 220,000 patients die of bladder cancer.[iii]It is estimated that in 2022, about 93,000 patients in China were diagnosed with bladder cancer, and about 41,000 patients died.[iv]
Senior Vice President and Head of Oncology Development at Astellas, MD, Master of Public HealthAhsan Arozullah
“Locally advanced or metastatic urothelial cancer is a life-threatening disease. Nearly half of confirmed patients die in China. The Drug Evaluation Center (CDE) accepted the license application for enfortumab vedotin and pembrolizumab as a complementary biologic, marking another step in our journey to provide this patient group with urgently needed and innovative treatment options.”
EV-302Professor Guo Jun, the main researcher in China, director of the Department of Melanoma and Urological Oncology at Peking University Cancer Hospital, and Vice Chairman and Secretary General of the Chinese Society of Clinical Oncology
The current first-line treatment strategy for advanced urothelial cancer in China is still platinum-containing chemotherapy, and there are no other approved first-line treatment options. However, the efficiency and progression-free survival of this first-line treatment plan, which mainly focuses on chemotherapy, need to be further improved, so clinically, there is an urgent need for first-line breakthrough treatment plans to further improve patients' prognosis. Global data from the EV-302 study established enfortumab vedotin combined with pembrolizumab as the first platinum-free chemotherapy first-line regimen. Compared with chemotherapy, this treatment plan can achieve clinically significant improvements in efficiency, nearly double the median progression-free survival period, and significantly prolong the survival of patients with advanced urothelial cancer.
Professor Huang Jian, Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou
Global research data on EV-302 confirm the remarkable efficacy and safety of enfortumab vedotin combined with pembrolizumab compared to chemotherapy in patients with advanced urothelial cancer. It is the first combination treatment plan superior to platinum-containing chemotherapy in the past 20-30 years, and is expected to become a new first-line standard treatment for advanced urothelial cancer. We hope to get approval from the regulatory authorities as soon as possible at home to benefit more Chinese patients as soon as possible.
The combined drug therapy SBLA for first-line treatment is based on the results of a phase 3 clinical trial EV-302 (also known as KEYNOTE-A39). The study found that combination therapy can improve overall survival (OS) and progression-free survival (PFS) in patients with previously untreated locally advanced or metastatic urothelial cancer (LA/muc), and the results are statistically significant and clinically significant. Safety results were consistent with previously reported combination therapy results, and no new safety issues were identified.
The NMPA is also reviewing enfortumab vedotin for the treatment of locally advanced or metastatic urothelial carcinoma (LA/muc) patients who have previously received PD-1/L1 and platinum-containing chemotherapy.
European Medicines Agency Committee for Medicines for Human Use (CHMP) and JapanWelfarelaborprovinces(MHLW) A combination therapy with enfortumab vedotin and pembrolizumab is also being reviewed. The US Food and Drug Administration (FDA) approved this combination therapy in December 2023.
Black box warning: severe skin reaction
- Enfortumab vedotin can cause serious and fatal skin adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). These skin adverse effects mainly occur during the first cycle of treatment, but may also occur in subsequent cycles.
- Monitor patients' skin reactions closely.
- For suspected SJS or TEN or severe skin reactions, discontinue enfortumab vedotin immediately and consider referral to professional care.
- Enfortumab vedotin should be permanently discontinued in patients with confirmed SJS or TEN, or grade 4 or recurrent grade 3 skin reactions.
Astellas cautionary statement
The statements in this press release relating to current plans, estimates, strategies and beliefs, and other non-historical facts are forward-looking statements about Astellas's future performance. These statements are based on management's current assumptions and beliefs, combined with currently available information, and involve known and unknown risks and uncertainties. Many factors may cause actual results to differ materially from those discussed in the forward-looking statements. These factors include, but are not limited to: (i) changes in general economic conditions and laws and regulations relating to the pharmaceutical market, (ii) currency exchange rate fluctuations, (iii) delays in new product launches, (iv) Astellas's inability to effectively sell existing and new products, (v) Astellas's inability to continue to effectively research and develop products accepted by customers in a competitive market, and (vi) infringement of Astellas intellectual property rights by third parties.
Information on pharmaceuticals (including products currently under development) contained in this press release does not constitute advertising or medical advice.
[i] Leow JJ, Liu Z, Tan TW, Lee YM, Yeo EK, Chong YL. Optimal Management of Upper Tract Urothelial Infections: Current Investigations. Onco Targets Ther. 2020; 13:1-15.
[ii] Petros FG. Epidemiology, clinical presentation, and evaluation of upper-tract urothelial carcinoma. Transl Androl Urol. 2020; 9 (4) :1794-8.
[iii] International Agency for Research on Cancer. Cancer Today: Globocan 2022 fact sheet (01-2024). 30-bladder-fact-sheet.pdf (who.int)
[iv] International Agency for Research on Cancer (IARC). Factual Fact Sheet. Lyon, France. 2022 (02-2024). Available at: 160-china-fact-sheet.pdf (who.int)