和誉医药在2024年美国定量药理学大会展示匹米替尼模型引导的剂量选择研究结果

和誉医药在此次ACoP大会上展示的壁报核心要点如下：

摘要编号：M-082

标题：综合药代动力学、安全性和有效性信息的模型以引导匹米替尼剂量选择

研究目的：

匹米替尼是一种口服、高活性、高选择性CSF-1R小分子抑制剂，对c-Kit和PDGFR的抑制作用极小，匹米替尼目前正在开发用于腱鞘巨细胞瘤（TGCT）患者的治疗，TGCT是一种罕见的局部侵袭性肿瘤，主要由CSF-1基因过表达引起^[1]。 本分析的目的是开发匹米替尼的群体药代动力学（popPK）模型，同时确定显著影响匹米替尼PK行为的内在/外在因素。 此外，还进行了暴露效应分析以描述匹米替尼暴露量与有效性/安全性终点之间的关系，以支持在TGCT患者的后续临床开发中的选择合适的剂量。

结论：

研究表征了匹米替尼群体药代动力学行为以及暴露和有效性/安全性终点的关系。 这些模型被用于确定匹米替尼的最佳剂量，研究结果支持50 mg QD做为匹米替尼在全球开发和治疗TGCT的推荐剂量。

ACoP 2024 ——Abbisko Therapeutics presents results on model-informed dose selection for pimicotinib (ABSK021) 

Nov 13, 2024, Abbisko Therapeutics (HKEX: 02256)  presented model-informed dose selection results for its self-discovered, orally available, highly selective, and potent small-molecule CSF-1R inhibitor, pimicotinib (ABSK021)，for the treatment of Tenosynovial Giant Cell Tumor (TGCT) at the American Conference on Pharmacometrics (ACoP) 2024. The study integrated drug pharmacokinetics, safety, and efficacy data to guide model-informed dose selection. These results support 50 mg QD as the recommended dose of pimicotinib for the global development and treatment of TGCT.

Key data points from the poster presented by Abbisko at this ACoP 2024 meeting include:

Poster number：M-082

Title：Integration of Pharmacokinetics, safety, and Efficacy into model-informed Dose Selection for Pimicotinib

Objectives:

Pimicotinib, an oral, highly potent and selective small-molecule antagonist of CSF-1R with minimum inhibition of c-Kit and PDGFR, is currently being developed for patients with Tenosynovial Giant Cell Tumor (TGCT), a rare type of locally aggressive neoplasm primarily caused by the overexpression of the CSF-1 gene^[1]. The objective of this analysis was to develop a population PK (popPK) model and concurrently identify intrinsic/extrinsic factors that significantly influence pimicotinib’s PK profile. Additionally, an exposure-response (E-R) analysis was performed to depict the relationship between pimicotinib exposure and efficacy/safety endpoints to support the selection of appropriate doses in subsequent clinical development in patients with TGCT.

Conclusions:

The study characterized pimicotinib popPK and E-R relationships and their association with efficacy and safety. These models were used to identify optimal dose selection for pimicotinib, supporting 50 mg QD as the recommended dose of pimicotinib for the global development and treatment of TGCT.

Reference：

1. Cannarile MA, et al. J Immunother Cancer. 2017; 5(1):53.