On the afternoon of July 11, 2025, XH-02 injection, a proprietary mRNA drug developed by PUMCH, was successfully administered to the first adult patient with hypoparathyroidism (HP). XH-02 injection is the world's first mRNA drug for adult hypoparathyroidism, developed by the nucleic acid therapy research team led by Zhang Shuyang, President of PUMCH. The drug is currently undergoing investigator-initiated trials (IIT). Following the first patient's dosing, no adverse reactions were observed, early pharmacodynamic indicators showed promising signals, and the patient was discharged on July 13.
HP is a disorder characterized by hypocalcemia and hyperphosphatemia resulting from insufficient secretion and/or inadequate effects of parathyroid hormone (PTH), which leads to corresponding symptoms. The most common cause is removal or damage to the parathyroid glands during neck surgery. Other causes include autoimmune diseases, hereditary conditions, and rare infiltrative diseases such as hemochromatosis, Wilson's disease and its metastases. Currently, HP treatment primarily involves calcium and active vitamin D supplementation, but these conventional therapies can only partially correct hypocalcemia and related symptoms without fundamentally addressing the underlying cause or effectively improving patients' quality of life. Replacement therapy represents the most pathophysiologically sound targeted treatment for this condition. However, existing PTH preparations are all peptide-based drugs with short half-lives, which makes it difficult to maintain stable PTH levels in blood. They continue to present challenges such as calcium fluctuations and inadequate urinary calcium control, rendering them unsuitable for HP treatment.
The XH-02 injection developed by the PUMCH research team is a nucleic acid drug. Guo Dan and Li Xiaogang, Director and Assistant Researcher of the Biobank respectively, explain that nucleic acid drugs are therapeutic macromolecular compounds based on nucleic acids (DNA or RNA) that deliver mRNA encoding specific proteins into human cells for treatment. With advantages including precise targeting, high specificity, favorable safety profiles, and shorter development timelines, they can address targets that conventional drugs cannot reach.
Chief Physician Dr. Qin Yan and Attending Physician Dr. Ai Sanxi from the Department of Nephrology explain that XH-02 injection is a targeted physiological PTH replacement therapy. Through sustained-release expression, it mimics the body's natural PTH secretion process to the greatest extent possible, thereby maintaining stable physiological PTH levels to correct hypocalcemia and hyperphosphatemia while reducing urinary calcium excretion and lowering the risk of chronic kidney complications.
Under rigorous evaluation and close monitoring by the research team, the first patient received XH-02 injection on the afternoon of July 11 at the clinical research ward of the National Infrastructure for Translational Medicine (PUMCH). According to Dr. Wang Ou, Chief Physician of Endocrinology, the administration went smoothly with excellent patient tolerance and no adverse reactions observed. Early pharmacodynamic indicators have shown promising results, and the team continues to closely monitor relevant biomarkers and clinical symptoms.
In recent years, supported by the National Infrastructure for Translational Medicine (PUMCH) and the National High Level Hospital Clinical Research Funding, PUMCH's multidisciplinary teams have addressed pressing clinical needs by conducting mRNA therapy proof-of-concept studies and IITs for protein replacement therapies that target both rare and common diseases. These tangible and impactful research outcomes have established a comprehensive innovation framework and model with PUMCH's distinctive approach that spans "basic research - technology development - outcome translation - clinical application".
Written by Guo Dan and Chen Xiao