Envafolimab, a subcutaneous PD-L1 antibody developed by Simcere Zaiming in collaboration with Alphamab Oncology (9966.HK) and 3D Medicines (1244.HK) in China, has recently been granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) for the treatment of gastric cancer and gastroesophageal junction (GEJ) cancer. This marks the third FDA orphan drug designation for Envafolimab, following previous designations for advanced bile duct cancer and soft tissue sarcoma.
Envafolimab (trade name: Enweida®) is the world’s first commercially available subcutaneous PD-L1 antibody. It was approved in China in November 2021 for the treatment of unresectable or metastatic microsatellite instability–high (MSI-H) or mismatch repair–deficient (dMMR) solid tumors. The drug has demonstrated promising antitumor activity in a Phase II clinical study involving patients with advanced gastric or esophagogastric junction adenocarcinoma. Results published in 2022 in the Chinese Journal of New Drugs showed that Envafolimab in combination with the FOLFOX regimen achieved an objective response rate (ORR) of 60% and a disease control rate (DCR) of 100%, with a favorable safety and tolerability profile. No treatment discontinuations or deaths were attributed to adverse events, supporting its potential as an effective immunotherapy option for gastric cancer.
Gastric cancer and gastroesophageal junction cancer are among the most common malignancies worldwide and remain associated with limited treatment options and poor prognosis for certain patient subgroups. According to projections based on the U.S. SEER database model, an estimated 26,890 new cases and 10,880 deaths occurred in the United States in 2024, with a five-year overall survival rate of less than 40%.
Envafolimab exerts its antitumor effect by blocking the interaction between PD-1 and PD-L1, thereby activating antitumor immune responses. With a molecular weight approximately half that of conventional monoclonal antibodies, it demonstrates enhanced tissue penetration and reaches tumor sites via the lymphatic circulation system. Enweida® also offers notable advantages in terms of convenience and safety, as it does not require intravenous infusion and can be administered in approximately 30 seconds. These characteristics make it particularly suitable for frail or elderly patients, as well as those who experience adverse reactions to intravenous administration. Enweida® is currently being evaluated in multiple clinical studies, including a completed Phase III trial in China for advanced bile duct cancer, with potential expansion into additional indications.
As of December 2025, Enweida® has received three FDA Orphan Drug Designations for the treatment of advanced bile duct cancer, soft tissue sarcoma, and gastric cancer/gastroesophageal junction cancer. In addition, it has been granted Breakthrough Therapy Designation by China’s National Medical Products Administration (NMPA) for the treatment of unresectable or metastatic solid tumors with high tumor mutational burden (TMB-H).