On June 2, the phase I/II clinical trial of GC301 adeno-associated virus (AAV) injection (“GC301 injection”), a gene therapy drug for infantile-onset Pompe disease, were launched at Peking Union Medical College Hospital (PUMCH). GC301 injection, the China-developed gene therapy drug that is globally the first to be approved for clinical trials for treating infantile-onset Pompe disease, holds the potential for treating patients with this disease more effectively.

Pompe disease is a rare lysosomal storage disease that is classified as infantile-onset or late-onset. The infantile-onset form usually appears by age 1, mainly involving skeletal and cardiac muscles. It progresses rapidly, with survival rates at 25.7%, 14.3% and 9.0% at 12, 18, and 24 months of age respectively. In 2006, the U.S. Food and Drug Administration (FDA) approved the use of enzyme replacement therapy with recombinant human alpha-glucosidase (rhGAA) for treating children with infantile-onset Pompe disease. However, this therapy needs to be continued throughout life and its success rate is influenced by a number of factors.

GC301 injection, independently developed by Beijing GeneCradle Pharmaceutical Co., Ltd., is a gene therapy drug with recombinant AAV as the systemically delivered vector carrying GAA gene expression sequence. The results of animal experiments showed that a single intravenous infusion could lead to the wide distribution of GAA in the heart, skeletal muscles, the liver and the nervous system, thereby achieving such purposes as long-term improvement of vitality, continuous removal of accumulated glycogen, and restoration of muscle strength. This drug has received the notification of drug clinical trial approval from the Center for Drug Evaluation, the National Medical Products Administration (CDE-NMPA), and approval from the clinical trial ethics committee of PUMCH, and was filed and publicized on the drug clinical trial registration and announcement platform.

▲Group picture of President Zhang Shuyang, Vice President Wu Peixin, and the rare disease research team and the drug R&D team of PUMCH in March, 2022

The “single-arm, multicenter, open-label phase I/II clinical trial to evaluate the safety and efficacy of GC301 injection for the treatment of patients with infantile-onset Pompe disease” is led by Qiu Zhengqing, Chief Physician of the Department of Pediatrics, and Han Xiaohong, Director of the Clinical Pharmacology Center, PUMCH. Subject recruitment has been initiated.

To support the R&D of innovative drugs for Pompe disease and other rare diseases, especially the early clinical studies of gene therapy drugs, the Clinical Pharmacology Center and the pediatric team of PUMCH have established the platform for immunogenicity evaluation of AAV vector-mediated gene therapy drugs and the platform for drug metabolomics analysis, and have taken the lead in taking on many research projects on rare diseases. Their efforts have laid a solid foundation for research on such fronts as pharmacodynamic biomarker discovery and natural history and pathogenesis of rare diseases.

Written by Gan Dingzhu and Zheng Xin

Picture courtesy of Han Xiaohong

Translated by Liu Haiyan

Edited by Wang Hongyun and Wang Yao