China’s National Medical Products Administration (NMPA) has officially approved Padcev (enfortumab vedotin) for the treatment of adult patients with locally advanced or metastatic urothelial cancer (la/mUC) who have previously undergone platinum-based chemotherapy and PD-1 or PD-L1 inhibitor therapies. This decision, made by the Center for Drug Evaluation (CDE) within the NMPA, marks an important milestone, offering a new therapeutic option for patients with advanced stages of urothelial cancer in China.
Approval Supported by Global EV-301 and China EV-203 Trials Demonstrating Improved Survival and Response Rates
Addressing a Critical Need in Urothelial Cancer Treatment
Urothelial cancer is an aggressive malignancy that affects both the lower and upper urinary tracts, including the bladder, urethra, ureter, and renal pelvis.
In 2022 alone, over 92,000 new cases of bladder cancer were diagnosed in China, with approximately 41,000 deaths resulting from the disease.
The survival outlook for patients with locally advanced or metastatic urothelial cancer remains poor, underscoring the urgent need for new treatments that can extend life expectancy.
Data Supporting the Approval
The NMPA’s approval of enfortumab vedotin is underpinned by robust data from the global EV-301 trial and the China-specific EV-203 trial. The EV-203 trial served as a bridging study to the EV-301 trial, a Phase 3 randomized study that has contributed to the global approval of enfortumab vedotin. EV-203 was a Phase 2, single-arm, open-label study involving Chinese patients with locally advanced or metastatic urothelial cancer who had previously received a PD-1/PD-L1 inhibitor and platinum-based chemotherapy.
The results demonstrated a statistically significant objective response rate (ORR) of 37.5%, as verified by an independent review committee, aligning with historical controls.
The efficacy, pharmacokinetics, and safety data from the EV-203 trial were consistent with the global data, with the majority of treatment-related adverse events being mild to moderate (grades 1–2).
Insights from the EV-203 Trial
The China EV-203 trial was specifically designed to assess the efficacy, safety, and pharmacokinetics of enfortumab vedotin in a Chinese population. A total of 40 patients with la/mUC were enrolled in the study.
The trial’s primary endpoint was the confirmed objective response rate (ORR), which was achieved in 37.5% of patients.
This included one patient who experienced a complete response and 14 patients who had partial responses. The safety profile was consistent with previous studies, with no new safety concerns identified. Most adverse events were mild to moderate, and two patients discontinued treatment due to adverse effects, including acute coronary syndrome and hyperglycemia accompanied by rash.
Global Context from the EV-301 Trial
The EV-301 trial was a large, Phase 3, open-label, randomized study that compared enfortumab vedotin with the physician’s choice of chemotherapy (docetaxel, paclitaxel, or vinflunine) in patients with la/mUC who had previously been treated with a PD-1/PD-L1 inhibitor and platinum-based chemotherapy. The primary endpoint was overall survival, with secondary endpoints including progression-free survival, overall response rate, duration of response, and disease control rate. Safety, tolerability, and quality-of-life assessments were also key components of the trial.
Results from EV-301 revealed a significant improvement in median overall survival for patients treated with enfortumab vedotin compared to those receiving chemotherapy (12.88 months vs. 8.97 months). Additionally, progression-free survival was longer in the enfortumab vedotin group (5.55 months) compared to the chemotherapy group (3.71 months).
The incidence of treatment-related adverse events was similar between the two groups, with 93.9% of patients in the enfortumab vedotin group and 91.8% in the chemotherapy group experiencing such events. The rate of severe adverse events (grade 3 or higher) was also comparable, occurring in 51.4% of patients treated with enfortumab vedotin and 49.8% of those receiving chemotherapy.
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