Clinical and Translational Science 发表HLX14临床I期研究数据

HLX14为复宏汉霖按照中国、欧盟和美国等生物类似药相关法规自主开发的地舒单抗生物类似药。复宏汉霖已于2022年与Organon达成授权许可和供应合作，授予其对包括HLX14在内的两款候选生物类似药在除中国以外的全球区域进行独家商业化的权益，协议覆盖美国、欧盟、加拿大等市场。2024年4月，HLX14用于治疗骨折高风险的绝经后妇女的骨质疏松症的国际多中心临床III期对照研究（NCT05352516）达到主要研究终点。基于一系列的头对头比对研究，HLX14的上市申请于2024年相继获得美国食品药品监督管理局（FDA）、欧洲药品管理局（EMA）和加拿大卫生部（Health Canda）受理。

NCT04534582研究是一项在中国健康成年男性受试者中开展的两阶段I期临床试验。第一阶段为开放标签、随机、平行对照、单次给药、双臂研究。主要研究目的为比较HLX14和欧盟市售的原研地舒单抗（PROLIA）在皮下给药后的药物代谢动力学参数，以进一步为第二部分临床研究方案设计提供依据。次要研究目的为比较HLX14与欧盟市售的原研地舒单抗（PROLIA）的药效学、安全性、耐受性和免疫原性。第二阶段是一项双盲、随机、平行对照、单次给药、四臂研究，主要目的为比较HLX14与美国、欧盟及中国市售的原研地舒单抗（参照药）的药物代谢动力学特征的相似性，次要目的为比较HLX14与参照药的药效学、安全性、耐受性和免疫原性。主要研究终点为AUC_0–t、C_max和AUC_0–inf。

研究数据显示，HLX14与美国、欧盟及中国市售的原研地舒单抗在药物代谢动力学特征和药效学具有高度相似性。第二阶段中，对于所有3个主要研究终点，HLX14和参照药的几何平均均值比（GMRs）均接近1，且其90%置信区间（CIs）均落在预设的等效性界值区间（0.8~1.25）范围内（AUC_0–t，0.91-1.13；C_max，0.91-1.13；AUC_0–inf，0.91-1.12）。

安全性与耐受性方面，HLX14相比参照药或市售其它地舒单抗生物类似药，未发现新的安全性信号。所有受试者均发生了治疗相关不良事件（TEAEs），其中大多数为1–2级。

HLX14有望为全球患者提供一种新的治疗选择，进一步丰富复宏汉霖在全球市场的产品布局。未来，复宏汉霖将持续以临床需求为导向，为全球患者提供更多可负担、疗效更好的治疗方案。

Clinical and Translational Science Publishes Phase 1 Clinical Results of Henlius’ HLX14

Recently, results from the phase 1 clinical study (NCT04534582) of Henlius’ denosumab biosimilar candidate HLX14 (a recombinant anti-RANKL human monoclonal antibody injection) was published in Clinical and Translational Science (IF 3.1). The results of this study suggest that HLX14 had highly similar pharmacokinetic (PK) and pharmacodynamics (PD), as well as comparable safety, tolerability, and immunogenicity to the US-, EU-, and China-sourced reference denosumab (Prolia^®). This study met all the pre-specified primary endpoints.

Henlius independently developed denosumab biosimilar candidate HLX14 in accordance with the NMPA, EMA, FDA, and other international biosimilar guidelines. In 2022, Henlius entered into a license and supply agreement with Organon for the exclusive commercialization rights to two biosimilar candidates, including HLX14. The agreement covers markets such as the United States, the European Union, and Canada. An exception from the agreement is China. In April 2024, the international multicenter phase 3 comparative clinical trial for HLX14 in postmenopausal women with osteoporosis at high risk for fracture met the primary endpoints. Based on a series of head-to-head comparison studies, the marketing applications of HLX14 have been accepted by the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), and Health Canada in 2024.

NCT04534582 is a two-part phase 1 clinical study in Chinese healthy adult male subjects. Part 1 is an open-label, randomised, parallel-controlled, single-dose, two-arm pilot study with the primary objective to compare the PK parameters of HLX14 and EU-sourced denosumab to provide further basis for the study design of part 2. The secondary objective of part 1 is to compare the PD, safety, tolerability, and immunogenicity of HLX14 and EU-sourced denosumab. Part 2 is a double-blind, randomised, parallel-controlled, single-dose, four-arm study with the primary objective to compare the PK similarity of HLX14 with US-, EU-, and China-sourced denosumab ("reference drug"). The secondary objective of Part 2 is to compare PD, safety, tolerability, and immunogenicity between HLX14 and the reference drugs. The primary study endpoints included AUC_0–t, C_max, and AUC_0–inf.

The results of this study suggest that HLX14 is highly similar to the originator denosumab from different sources in PK and PD characteristics. In Part 2, in pairwise comparisons of HLX14 to the reference drugs, the resulting geometric mean ratios (GMRs) were all close to 1 for all three primary endpoints, and their 90% CIs all fell entirely within the pre-specified similarity margins of 0.80 to 1.25 (AUC_0–t， 0.91–1.13; C_max, 0.91–1.13; AUC_0–inf, 0.91–1.12).

In terms of safety and tolerability,  no new safety signal was identified in the HLX14 group as compared to the denosumab groups in the study, or to other denosumab biosimilars. Although all participants experienced treatment-related adverse events (TEAEs), most were grade 1–2.

HLX14 is expected to serve as an additional  treatment option for patients worldwide and further enriches Henlius’ product portfolio in the global market. In the future, Henlius will continue to focus on clinical needs and provide more affordable and effective treatment options for patients worldwide.

媒体：PR@Henlius.com

投资者：IR@Henlius.com