“暂时连接”(TransCon)技术在罕见内分泌疾病治疗中的研究进展

doi:10.5246/jcps.2026.01.001

摘要/Abstract

摘要：

遗传性甲状旁腺功能减退症(HP)、软骨发育不全(ACH)及原发性生长激素缺乏症(GHD)已于2023年被列入中国《第二批罕见病目录》。目前, 针对部分罕见内分泌疾病的最优治疗方案已开展了大量研究, 其中长效治疗制剂的开发被认为是改善疗效、提升患者依从性的关键策略, 尤其是在每日皮下注射带来显著负担的背景下。然而, 针对“暂时连接”(Transient Conjugation, TransCon)技术在此类疾病治疗中潜力的研究仍较为有限。该技术通过将活性药物转化为前药形式, 从而延长其半衰期并降低给药频率, 在改善罕见内分泌疾病治疗模式方面具有广阔前景。本研究为首次系统综述TransCon技术在HP、ACH与GHD中的研究进展, 内容涵盖其药代动力学特征、疗效、安全性、耐受性及患者报告结果, 并与传统治疗进行比较, 旨在为相关疾病的制剂研发与临床治疗提供参考依据。

关键词: 暂时连接技术, 前药, 长效制剂, 罕见内分泌疾病

Abstract:

Genetic hypoparathyroidism (HP), achondroplasia (ACH), and primary growth hormone deficiency (GHD) are listed as rare diseases in the second List of Rare Diseases in China in 2023. Numerous studies have explored optimal therapies for certain rare endocrine diseases, and the development of long-acting therapeutic agents has been considered a key strategy for improving treatment outcomes, especially given the challenges associated with daily subcutaneous injections. However, limited attention has been given to the potential of "transient conjugation" (TransCon) technology, a platform designed to convert drugs into prodrug forms, thereby extending their half-lives and reducing dosing frequency, which demonstrates promise as a more convenient treatment option for these conditions. This is the first study to review the research progress of TransCon technology in the treatment of HP, ACH, and GHD, focusing on its pharmacokinetic properties, efficacy, safety, tolerability, and patient-reported outcomes in comparison with conventional therapies, in order to provide a reference for formulation development and clinical management of these rare endocrine diseases.

Key words: TransCon, Prodrug, Long-acting, Rare endocrine diseases

Supporting:

刘清扬, 徐天宇, 杜佳毅, 唐彦. “暂时连接”(TransCon)技术在罕见内分泌疾病治疗中的研究进展[J]. 中国药学(英文版), 2026, 35(1): 1-15.

Qingyang Liu, Tianyu Xu, Jiayi Du, Yan Tang. Advances in “transient conjugation” (TransCon) technology for treating rare endocrine diseases[J]. Journal of Chinese Pharmaceutical Sciences, 2026, 35(1): 1-15.

图/表 4

Table 1. Overview of the clinical development progress of TransCon products.

Figure 1. The structure of TransCon PTH and the mechanism of drug release after subcutaneous injection. Created with BioRender.com.

Figure 2. The mechanism of drug release after subcutaneous injection of TransCon CNP. Created with BioRender.com.

Figure 3. Structure of TransCon GH and the mechanism of gradual drug release following subcutaneous administration. Created with BioRender.com.

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