A randomized, double-blind, parallel-group, active-controlled comparative study to evaluate the efficacy, safety, pharmacokinetics, and immunogenicity of LY06006 compared with EU-Prolia in postmenopausal women with osteoporosis

开始日期2023-05-25

申办/合作机构

山东博安生物技术股份有限公司

NCT04859569 / Recruiting临床3期

A Phase III Study Comparing Efficacy and Safety of LY01011 and Xgeva®(Denosumab) in Patients With Bone Metastases From Solid Tumors

This is a multicenter，randomized, double-blind, active-controlled, parallel-group study comparing efficacy and safety of LY01011 (recombinant anti-RANKL human monoclonal antibody injection) and Xgeva® in patients with bone metastases from solid tumors.

开始日期2021-04-30

申办/合作机构

绿叶制药

CTR20210226 / Completed临床3期

比较重组抗RANKL全人单克隆抗体注射液（LY01011）与Xgeva®（地舒单抗注射液）治疗实体瘤骨转移患者有效性和安全性的随机、双盲、平行、阳性药对照、多中心临床研究

以第13周尿肌酐校正的尿I型胶原交联N端肽（uNTx/uCr）距基线值变化的自然对数值为主要终点指标，比较LY01011与Xgeva®治疗实体瘤骨转移患者有效性的相似性

开始日期2021-04-26

申办/合作机构

山东博安生物技术股份有限公司

100 项与地舒单抗生物类似药 (山东博安生物) 相关的临床结果

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100 项与地舒单抗生物类似药 (山东博安生物) 相关的转化医学

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100 项与地舒单抗生物类似药 (山东博安生物) 相关的专利（医药）

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项与地舒单抗生物类似药 (山东博安生物) 相关的文献（医药）

2023-10-01·Journal of bone oncology

A randomized trial comparing LY01011, biosimilar candidate, with the reference product denosumab (Xgeva®) in healthy Chinese subjects.

Article

作者: Dou, Changlin ; Ding, Yanhua ; Liu, Yusi ; Guo, Shuren

Background:

Complications of bone metastases such as skeletal-related events lead to the impaired functional status and quality of life including death in patients with bone metastasis from solid tumors. Denosumab (XGEVA®) is indicated for the prevention of skeletal-related events in bone metastasis patients with solid tumors. The biosimilar product LY01011, a fully human anti-receptor activator of nuclear factor kappa-B ligand monoclonal antibody, was developed to be compared with the reference product denosumab.

Material and methods:

A randomized, double-blind, single-dose, parallel-controlled phase 1 study was conducted in healthy Chinese subjects. A total of 168 enrolled subjects were randomly assigned in a 1:1 ratio to receive a single 120 mg dose of LY01011 (n = 85) or denosumab (n = 83) subcutaneously. The primary pharmacokinetic (PK) parameters, including maximum plasma concentration (C_max) and area under the concentration-time curve from time zero to last quantifiable concentration (AUC_0→t), were collected and measured for evaluation. Other secondary PK parameters included AUC_{0- ∞}, T_max, CL/F, λ_z, t_1/2, V_d/F, etc. Pharmacodynamics (PD), safety and immunogenicity profiles were also accounted for data analysis.

Results:

The geometric mean ratios (GMRs) of LY01011 and denosumab for the primary PK parameters such as C_max and AUC_0→t were 98.13% and 100.32%. The 90% confidence intervals (CIs) were all within the acceptance range of 80%-125%. The GMRs of the PD parameters including AUEC_0→t and E_max were 98.71% and 99.80%, which fell within the pre-defined acceptance range of 80%-125%. The results also demonstrated PK similarity even if Cmax and AUC_0→∞ had been used as primary endpoints. Safety profiles were tolerable and similar between groups. 4 (4.7%) and 2 (2.4%) subjects had experienced Grade 3 or above treatment-emergent adverse events (TEAEs) in LY01011 group and denosumab group. 3 subjects were reported to have serious adverse events (SAEs). None of the Grade 3 or above TEAEs and SAEs were related to the study drug, LY01011. No subject was tested anti-drug antibody (ADA) positive in both groups prior to the study drug administration. Following the study drug administration, only one subject in denosumab group was tested ADA positive, whereas no subject with ADA positive was reported in LY01011 group. No neutralizing antibody (Nab) was detected in either group throughout the study.

Conclusions:

The study demonstrated PK and PD similarity of LY01011, a denosumab biosimilar, to denosumab in healthy Chinese subjects, with comparable safety and immunogenicity profiles.

2023-01-01·Journal of Orthopaedic Translation

Denosumab biosimilar (LY06006) in Chinese postmenopausal osteoporotic women: A randomized, double-blind, placebo-controlled, multicenter phase III study

Article

作者: Wang, Guang ; Hong, Dun ; Wang, Chuansuo ; Wang, Xinjia ; Cheng, Zhifeng ; Liu, Yonghua ; Xue, Qingyun ; Shang, Xianwen ; Xiao, Xinhua ; Fu, Liujun ; Shen, Lin ; Yang, Tao ; Zhang, Xiaomei ; Zhou, Huimin ; Li, Yukun ; Guo, Shuren ; Zhang, Xinchao ; Liu, Lijun ; Cheng, Jinluo ; You, Li ; Zhang, Shimin ; Tang, Xin ; Hua, Fei ; Zhang, Hao ; Deng, Chunying ; Huo, Yanan ; Xiao, Jianzhong ; Cheng, Xigao ; Shen, Jie ; Dong, Jin ; Zhang, Yawei ; Wang, Li ; Jiang, Chengyan ; Lei, Chen ; Guan, Xiaoling ; Gu, Jiemei ; Zhang, Panjun ; Hu, Ling ; Chen, Jianting ; Du, Xiaohong ; Ding, Yue ; Xu, Youjia ; Yuan, Lingqing ; Li, Qifu ; Xu, Jin ; Pan, Tianrong ; Li, Lixin ; Wang, Kai ; Yao, Qi ; Zhang, Zhenlin ; Zhang, Ying ; Liu, Wei

Objectives:

This study assessed the efficacy, safety, pharmacokinetics (PK), and immunogenicity profiles of a denosumab biosimilar (LY06006) in Chinese postmenopausal osteoporotic women with a high risk of fracture.

Methods:

In this multicenter, randomized, double-blind, placebo-controlled, phase 3 trial, 448 postmenopausal women aged 50-85 years with osteoporosis were enrolled at 49 centers in China and were randomly assigned (3:1) to receive 60 mg of the denosumab biosimilar (LY06006) or placebo subcutaneously every 6 months for 1 year. Lumbar spine bone mineral density (BMD) change was the primary endpoint.

Results:

Of the 448 randomized patients, 409 (LY06006, n = 311; placebo, n = 98) completed the study. All 448 (100.0%) subjects were included in the intent-to-treat (ITT) trial, 427 (95.3%) were included in the full analysis set (FAS), 408 (91.1%) were included in the per protocol set (PPS), 446 (99.6%) were included in the safety set (SS), and 336 (75.0%) were included in the pharmacokinetics concentration set (PKCs). For the primary endpoint, a 4.71% (95% CI, 3.81%, 5.60%) treatment difference in percent change in lumbar spine BMD from baseline to month 12 was observed in the LY06006 group compared with the placebo group (P < 0.0001). For the secondary endpoints, LY06006 was associated with increased lumbar spine BMD levels measured at month 6, BMD levels at the femoral neck, total hip, and trochanter measured at months 6 and 12 and reduced serum C-terminal telopeptide of type 1 collagen (CTX) and procollagen type 1 N-peptide (P1NP) levels at months 1, 6, and 12. Safety analysis was based on the safety analysis set (SS), and 264 (78.6%) subjects in the LY06006 group and 83 (75.5%) in the placebo group experienced adverse events (AEs). Most events were mild or moderate and not related to the study drugs.

Conclusion:

In postmenopausal women with a high risk of fracture, LY06006 increased the BMD and decreased bone resorption; thus, LY06006 might be an effective treatment for osteoporosis. LY06006 was generally safe and well tolerated without unexpected adverse reactions, similar to the reference drug Prolia®. The characteristics of effectiveness and safety were similar to those reported in previous studies.

The translational potential of this article:

In this multi-center, randomized, double-blind, placebo-controlled phase 3 study, LY06006 showed substantially efficacy to increase BMD and well tolerance without unexpected adverse reactions, which is comparable to the reference drug Prolia ®. The presented results are encouraging and can offer some valuable evidence for the clinical practice.

2022-10-03·Expert Opinion on Investigational Drugs

Pharmacokinetics, pharmacodynamics, safety, and immunogenicity of a biosimilar of denosumab (LY06006): a randomized, double-blind, single-dose, parallel-controlled clinical study in healthy Chinese subjects

Article

作者: Wu, Qian ; Huang, Jie ; Yang, Guoping ; Chen, Honghui ; Xiang, Yuxia ; Yang, Xiaoyan ; Dou, Changlin ; Yang, Shuang ; Wang, Siyi ; Wu, Shuting

OBJECTIVES:

To compare the pharmacokinetics (PK), pharmacodynamics (PD), safety, and immunogenicity of LY06006 (denosumab biosimilar) and denosumab in healthy Chinese adult male subjects.

METHODS:

In this randomized, double-blind, parallel-controlled, single-dose, comparative biosimilar study, a total of 168 subjects received 60 mg of LY06006 or denosumab by subcutaneous (SC) abdominal injections in a 1:1 ratio with a follow-up period of 168 days.

RESULTS:

After a single SC abdominal injection of 60 mg LY06006/denosumab, the geometric mean ratio of the main pharmacokinetic parameters, C_max and AUC_0-∞, of the two drugs were 97.57% and 104.27%, respectively; the geometric mean ratio of the main pharmacodynamic parameters AUEC_0-t and E_max, were 101.00% and 99.64%, respectively, and the 90% confidence interval was observed to be within 80-125%. The subjects in the test group (LY06006) and control group (denosumab) were all negative for anti-drug antibody (ADA). The incidence and severity of treatment-emergent adverse events (TEAEs)were similar for both groups, and no grade 3 or higher TEAEs occurred in either group.

CONCLUSIONS:

This study demonstrated that LY06006 and denosumab have similar characteristics and bioequivalence in pharmacokinetics. Moreover, they had similar pharmacodynamic profiles, safety, and immunogenicity.

CLINICAL TRIAL REGISTRATION:

www.clinicaltrials.gov identifier is NCT04973722.

项与地舒单抗生物类似药 (山东博安生物) 相关的新闻（医药）

2024-04-30

·医药魔方

齐鲁制药「地舒单抗」生物类似药获批上市，治疗骨巨细胞瘤

4月30日，齐鲁制药的靶向抗肿瘤药物鲁达欣®（地舒单抗注射液）正式获得上市许可批准，用于治疗不可手术切除或者手术切除可能导致严重功能障碍的骨巨细胞瘤，包括成人和骨骼发育成熟(定义为至少1处成熟长骨且体重≥45kg)的青少年患者。地舒单抗是一款IgG2全人源化单克隆抗体，可阻止核因子κB受体活化因子配体（RANKL）激活破骨细胞及其前体表面的受体RANK，阻断RANKL/RANK相互作用可抑制破骨细胞形成、功能和存活，从而减少骨吸收，增加骨皮质和骨小梁的骨量和强度。原研地舒单抗由安进开发上市，根据规格和适应症分为两个不同的品牌，分别为：Xgeva（安加维，70 mg/ml）和Prolia（普罗力，60 mg/ml）。其中Xgeva用于治疗癌症相关骨病，Prolia用于治疗骨质疏松。目前，国内开发地舒单抗生物类似药的企业有15家，其中博安生物的博优倍已于2022年11月获批上市，是全球首个上市的Prolia生物类似药；迈威生物的迈利舒也于2023年3月获批上市，是全球第2款上市的Prolia生物类似药；随后2023年10月，齐鲁制药的Prolia生物类似药鲁可欣也获批上市。2024年4月，迈威生物的迈卫健获批上市，是国内首款获批上市的安加维生物类似药。Copyright © 2024 PHARMCUBE. All Rights Reserved.欢迎转发分享及合理引用，引用时请在显要位置标明文章来源；如需转载，请给微信公众号后台留言或发送消息，并注明公众号名称及ID。免责申明：本微信文章中的信息仅供一般参考之用，不可直接作为决策内容，医药魔方不对任何主体因使用本文内容而导致的任何损失承担责任。

生物类似药上市批准

2024-04-14

·药渡

不想输的Biotech：借钱也要把临床做下去

现金流危机，几乎是当下笼罩在所有中小Biotech身上的共同阴影。作为自身造血能力欠缺的Biotech，如果难以从资本市场拿到足够的股权融资把研发做下去，就如同让战士端起没有子弹的机枪去冲锋，一切宏大叙事都彻底无从谈起。结局大抵有两种：幸运者卖身给大药企，大树底下好乘凉；不幸者现金彻底耗尽，关门大吉。更多的Biotech，既没有被大药企看中，也暂时没有到山穷水尽的地步，只能选择各种方式自救。借钱推进临床研发，于是也成为一种方式。2024年4月12日，港股上市的Biotech公司博安生物发布公告，公司与中国金谷国际信托有限责任公司订立一项贷款融资协议，由后者作为资金出借方，向博安生物提供人民币3亿元的定期贷款融资。同时，博安生物的控股股东，同意以博安生物7438万股的H股，作为公司偿还融资贷款的担保。按照最新的港股二级市场交易价格，该笔股份对应的价值约7.8亿港币，因此该笔贷款的质押率在50%左右。博安生物表示，拟将该融资的所得款项用于其产品管线的临床开发、商业化生产线的扩张、应付款项的结清及短期贷款的偿还。以股权形式融来的资金，如果研发成功则收益共享，一旦临床失败则风险共担；但是以债权形式融来的资金，即使研发失败，也要偿还本金，因此对于Biotech企业来说，债券融资并不常用。敢于选择这个路径，除了近期港股二级市场的融资可能性确实微乎其微以外，博安生物相对确定的基本面，也是一大因素。这是一家有6亿多收入的Biotech公司。2024年3月，博安生物发布2023年财报，公司实现营业收入6.2亿元人民币，同比增长20%，当期经营性现金流流入和流出基本达到持平，并于2023年下半年首次实现扭亏为盈。博安生物的主要收入，来源于两款生物类似药：博优诺（贝伐珠单抗，肿瘤领域）和博优倍（地舒单抗，骨松领域），二者均被纳入新版国家医保目录。但是博安生物仍然没有实现全年盈利，2023年仍然亏损1.2亿元。更为严峻的是，公司账上现金不多了，根据2023年财报数据显示，公司账上现金以及现金等价物仅剩2亿人民币，但是仍然有数量不菲的研发管线在推进之中。在生物类似药领域，博安生物还有六款产品接近商业化：BA1102（地舒单抗，肿瘤领域）、BA5101（度拉糖肽）、BA9101（阿柏西普）、BA1104（纳武利尤单抗）、BA1104（纳武利尤单抗）、BA6101（地舒单抗，骨松领域）。其中BA1102在国内已处于上市申请（BLA）审评阶段，BA5101为全球首个完成Ⅲ期临床试验的度易达生物类似药，目前已经处于BLA准备阶段，而BA1104则为国内首个开展Ⅲ期临床试验的欧狄沃生物类似药。接近商业化，也就是还没有商业化，无论是完成上市申请流程，还是此后的商业化启动，都是需要继续往里投资金的。除了生物类似药，博安生物还有一堆创新药管线，大都处于临床I期或者临床II期：BA2101（长效抗IL-4Rα单抗）进入Ⅱ期临床阶段；BA1202（抗CEA/CD3双抗）处于Ⅰ期临床阶段，为国内首个进入临床的、靶向CEA和CD3的创新双抗；BA1106（非IL-2阻断型抗CD25抗体）处于Ⅰ期临床阶段，是国内首个进入临床的、用于治疗实体瘤的抗CD25创新抗体；BA1301（抗Claudin18.2 ADC）和BA1105（抗Claudin18.2单抗）均处于Ⅰ期临床阶段。如此众多的研发管线，2亿元的现金，无异于杯水车薪，但是这么多接近商业化的管线，无论如何也不可能放弃，于是举债经营成为一个选项。如果后续生物类似药的商业化进程顺利，公司的正向现金流进一步增加，举债经营的风险是可控的。但是后续还有众多处于早期临床阶段的创新药管线，每一个都是吞金巨兽，可能只能寄希望于成功的对外BD授权了。免责声明“药渡”公众号所转载该篇文章来源于其他公众号平台，主要目的在于分享行业相关知识，传递当前最新资讯。图片、文章版权均属于原作者所有，如有侵权，请及时告知，我们会在24小时内删除相关信息。微信公众号的推送规则又双叒叕改啦，如果您不点个“在看”或者没设为"星标"，我们可能就消散在茫茫文海之中~点这里，千万不要错过药渡的最新消息哦！

财报临床3期生物类似药

2024-04-14

·Pharma CMC

质押7438.7万股H股，博安生物贷款融资3亿元！用于临床开发与扩大生产

4月12日，博安生物发布公告，公司与中国金谷国际信托有限责任公司（「贷款人」）订立一项贷款融资，据此，贷款人同意向本公司提供人民币300,000,000元的定期贷款（「融资」）。博安生物控股股东山东绿叶制药有限公司，同意以贷款人为受益人质押博安生物74,387,153股H股，作为偿还融资贷款的担保。博安生物拟将该融资的所得款项用于（其中包括）为其产品管线的临床开发、其商业化生产线的扩张、应付款项的结清及短期贷款的偿还提供资金。据此前博安生物发布的年报显示，博安生物2023年的营业收入同比增长20%，达到人民币618.1百万元。同时，销售、研发及管理费用的三项费用总额同比下降23%。当期亏损下降至人民币119.4百万元，同比大幅收窄64%。经营性现金流流入和流出基本达到持平；2023年下半年首次实现扭亏为盈。截至2023年12月31日，博安生物拥有博优诺®（贝伐珠单抗注射液）、博优倍（®BA6101，地舒单抗注射液）2款商业化产品，以及多款处于开发阶段的候选药物，其研发团队约为300人。来源：博安生物公告

临床1期引进/卖出财报

100 项与地舒单抗生物类似药 (山东博安生物) 相关的药物交易

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外链

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研发状态

适应症	最高研发状态	国家/地区	公司
骨转移癌	申请上市	-	绿叶制药更多
实体瘤	临床3期	中国更多	山东博安生物技术股份有限公司更多
骨巨细胞瘤	临床3期	中国更多	Luye Pharma AG 更多
骨质疏松症	临床1期	-	Luye Pharma AG 更多
骨癌	无进展	中国更多	山东博安生物技术股份有限公司更多

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04859569 (ASCO2023) 人工标引	临床3期	实体瘤	850	LY01011	壓淵顧鬱壓鑰衊簾築廠(網壓淵選築遞膚簾鬱選) = 簾鹽構淵觸選觸繭夢夢糧壓襯憲積醖襯餘築鹹 (齋遞壓築廠觸範壓餘構 ) 更多	相似	2023-05-31
				LY01011+denosumab	壓淵顧鬱壓鑰衊簾築廠(網壓淵選築遞膚簾鬱選) = 艱鹹襯醖壓繭憲鹹獵廠糧壓襯憲積醖襯餘築鹹 (齋遞壓築廠觸範壓餘構 ) 更多
NCT05060406 (Pubmed) 人工标引	临床3期	骨质疏松性骨折	409	LY06006	蓋窪醖網顧壓糧襯窪夢(鏇範襯糧製壓觸範艱壓): difference = 4.71 (95% CI, 3.81 ~ 5.60), P-Value = <0.0001	积极	2022-10-29
				Placebo
NCT04973722 (Pubmed) 人工标引	临床1期	-	168	LY06006	餘衊顧壓夢鹹遞膚襯窪(願膚衊鬱壓鑰繭衊醖觸) = 觸築獵構鑰觸膚觸繭淵觸餘壓遞選鑰廠艱鬱窪 (廠鬱繭鹽廠壓鹹醖鹹艱 ) 更多	积极	2022-08-31
				denosumab	-