The purpose of this study is to evaluate i) the effect of multiple doses of vosoritide and ii) the effect of the therapeutic dose of vosoritide compared to human growth hormone (hGH), in children with idiopathic short stature (ISS).

开始日期2024-09-01

申办/合作机构

BioMarin Pharmaceutical, Inc.

NCT05849389 / Recruiting临床2期IIT

Vosoritide for Treatment of Short Stature in Girls With Turner Syndrome

Turner syndrome (TS) is characterized by a missing whole or part of the second sex chromosome in a phenotypic female, resulting in short stature due to haploinsufficiency of the short-stature homeobox-containing (SHOX) gene. Growth hormone (GH) is an approved therapy for this condition, although not associated with GH deficiency, and benefits are modest. Vosoritide, a C-type natriuretic peptide (CNP) analog, targets chondrocytes within the growth plate leading to increased cell proliferation and hypertrophy. We hypothesize that patients with TS and short stature will respond to vosoritide treatment leading to increased growth velocity. This study will enroll pre-pubertal girls with TS who are either naïve to GH or have had a poor response to GH therapy. All subjects will be treated with vosoritide for 12 months and will be assessed for safety monitoring and improvement in height outcomes. Annualized growth velocity (AGV) on vosoritide will be compared to AGV in the 6-18 months prior to initiation of vosoritide based on historical data available in the medical record. Subjects with a positive response to therapy will be given the option to continue in the extension phase of the study during which they will continue to receive vosoritide until growth cessation.

开始日期2024-03-01

申办/合作机构

Children's National Research Institute

NCT05813314 / Terminated临床1期

A Phase 1, Randomized, Open-Label, Sponsor-Open, Two-Sequence, Two-Period Crossover Study to Investigate the Bioequivalence of a Single Subcutaneous Dose of BMN 111 Administered Using Either a Vial and Syringe or Injector Pen in Healthy Adult Participants

The purpose of this study is to establish the bioequivalence of a single SC dose of BMN 111 administered using a vial and syringe versus using an injector pen.

开始日期2023-03-15

申办/合作机构

BioMarin Pharmaceutical, Inc.

100 项与伏索利肽相关的临床结果

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100 项与伏索利肽相关的转化医学

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100 项与伏索利肽相关的专利（医药）

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项与伏索利肽相关的文献（医药）

2024-02-09·Deutsches Arzteblatt international

The Treatment of Growth Disorders in Childhood and Adolescence.

Review

作者: Joachim Woelfle ; Dirk Schnabel ; Gerhard Binder

BACKGROUND:

3% of all children are unusually short, and 3% are unusually tall. New approaches have broadened the range of therapeutic options in treating growth disorders.

METHODS:

This review is based on publications retrieved by a selective review of the literature and on the authors' clinical experience.

RESULTS:

Pituitary growth hormone deficiency is treated with recombinant growth hormone. Long-acting preparations of this type became available recently, but their long-term safety and efficacy are still unknown. Vosoritide, a CNP analogue, has also been approved for the treatment of achondroplasia, and severe primary deficiency of insulin-like growth factor 1 (IGF-1) can be treated with recombinant IGF-1. In the treatment of excessively tall stature, new information on the safety of growth-attenuating treatment and an altered perception of above-average height in society have led to a change in management.

CONCLUSION:

There are new options for the treatment of rare causes of short stature, while new information on the safety of treatment strategies for excessive tallness have led to a reconsideration of surgical intervention. There is insufficient evidence on the benefits and risks of supraphysiological GH therapy and of newer treatment options for which there are as yet no robust data on adult height. Therefore, before any treatment is provided, physicians should give patients and their families detailed information and discuss their expectations from treatment and the goals that treatment can be expected to achieve.

2023-11-17·The Lancet. Child & adolescent health

Vosoritide therapy in children with achondroplasia aged 3-59 months: a multinational, randomised, double-blind, placebo-controlled, phase 2 trial.

Article

作者: Ravi Savarirayan ; William R Wilcox ; Paul Harmatz ; John Phillips ; Lynda E Polgreen ; Louise Tofts ; Keiichi Ozono ; Paul Arundel ; Melita Irving ; Carlos A Bacino ; Donald Basel ; Michael B Bober ; Joel Charrow ; Hiroshi Mochizuki ; Yumiko Kotani ; Howard M Saal ; Clare Army ; George Jeha ; Yulan Qi ; Lynn Han ; Elena Fisheleva ; Alice Huntsman-Labed ; Jonathan Day

BACKGROUND:

Vosoritide is a recombinant C-type natriuretic peptide analogue that increases annualised growth velocity in children with achondroplasia aged 5-18 years. We aimed to assess the safety and efficacy of vosoritide in infants and children younger than 5 years.

METHODS:

This double-blind, randomised, placebo-controlled, phase 2 trial was done in 16 hospitals across Australia, Japan, the UK, and the USA. Children younger than 60 months with a clinical diagnosis of achondroplasia confirmed by genetic testing and who had completed a baseline growth study or observation period were enrolled into one of three sequential cohorts based on age at screening: 24-59 months (cohort 1); 6-23 months (cohort 2); and 0-5 months (cohort 3). Each cohort included sentinels who received vosoritide to determine appropriate daily drug dose, with the remainder randomly assigned (1:1) within each age stratum (except in Japan, where participants were randomly assigned within each cohort) to receive daily subcutaneous injections of vosoritide (30·0 μg/kg for infants aged 0-23 months; 15·0 μg/kg for children aged 24-59 months) or placebo for 52 weeks. Participants, caregivers, investigators, and the sponsor were masked to treatment assignment. The first primary outcome was safety and tolerability, assessed in all participants who received at least one study dose. The second primary outcome was change in height Z score at 52 weeks from baseline, analysed in all randomly assigned participants. This trial is registered with EudraCT, 2016-003826-18, and ClinicalTrials.gov, NCT03583697.

FINDINGS:

Between May 13, 2018, and March 1, 2021, 75 participants were recruited (37 [49%] females). 11 were assigned as sentinels, whereas 32 were randomly assigned to receive vosoritide and 32 placebo. Two participants discontinued treatment and the study: one in the vosoritide group (death) and one in the placebo group (withdrawal). Adverse events occurred in all 75 (100%) participants (annual rate 204·5 adverse events per patient in the vosoritide group and 73·6 per patient in the placebo group), most of which were transient injection-site reactions and injection-site erythema. Serious adverse events occurred in three (7%) participants in the vosoritide group (decreased oxygen saturation, respiratory syncytial virus bronchiolitis and sudden infant death syndrome, and pneumonia) and six (19%) participants in the placebo group (petit mal epilepsy, autism, gastroenteritis, vomiting and parainfluenza virus infection, respiratory distress, and skull fracture and otitis media). The least-squares mean difference for change from baseline in height Z score between the vosoritide and placebo groups was 0·25 (95% CI -0·02 to 0·53).

INTERPRETATION:

Children with achondroplasia aged 3-59 months receiving vosoritide for 52 weeks had a mild adverse event profile and gain in the change in height Z score from baseline.

FUNDING:

BioMarin Pharmaceutical.

2023-11-01·Intractable & rare diseases research

Vosoritide, a miracle drug, covering unmet need in achondroplasia: A regulatory update.

Article

作者: Simran ; Kirthiga Devi S S ; Sabanis Chetan Dushantrao ; Ramesh Joga ; Sandeep Kumar

Dwarfism is a rare condition characterized by small stature. Achondroplasia is predominantly considered the leading cause of dwarfism. Although the condition is not life-threatening, it dramatically impacts the social life of the patient. The United States Food and Drug Administration (US FDA) first approved the drug Voxzogo (vosoritide) for achondroplasia. The drug also received approval from the European Medicines Agency (EMA) via the centralized procedure. The drug is associated with a decrease in blood pressure, a severe adverse event. However, this adverse event/risk has been overcome by benefits, i.e. fulfilling of unmet medical need. In the United States, the drug received accelerated approval as it satisfied the criteria of rare pediatric disease. This review includes a detailed orphan drug approval process with particular reference to vosoritide, which is considered a milestone for the treatment of achondroplasia.

项与伏索利肽相关的新闻（医药）

2024-03-26

·同写意

埋伏？那些可能被收购的生物制药公司

大会由扬州市人民政府主办，同写意专业策划，以“打造生物医药新质生产力”为主题，邀请众多行业领袖和先锋人物一起取势明道，就如何打造中国医药新质生产力，面向未来创新药如何立项，资本寒冬下的创新药BD与出海，GLP-1&小核酸药物以及抗体药的质量与生产四大主题展开深度研讨，为行业发展提供方向性指引。每年国际大药企都会收购一些处于商业化阶段的生物制药公司，来补充自身的商业化品种，本文根据最新的销售数据，遴选了8家潜在被收购的标的公司。图1 2021年收购金额TOP10标的图2 2022年收购金额TOP10标的图3 2023年收购金额TOP10标的图4 潜在被收购标的（丰硕创投整理）1Argenx基本信息：重点品种Vyvgart在2023年的净销售额为11.91亿美元，该司2023年产品净销售额为11.91亿美元，最新市值为238.8亿美元。 Vyvgart：在2021年12月17日获得FDA批准，成为当时第一个也是唯一一个获批的FcRn阻滞剂，用于治疗AChR抗体阳性的成人全身性重症肌无力（gMG）。ADAPT试验结果发表在《柳叶刀神经病学》上。2Harmony Biosciences基本信息：重点品种Wakix在2023年的净销售额为5.82亿美元，该司2023年产品净销售额为5.82亿美元，最新市值为18.91亿美元。Wakix：在2019年8月14日获得FDA批准，成为当时第一个也是唯一一个获批用于治疗成人日间过度嗜睡（EDS）的发作性睡病且未被美国缉毒局（EDA）列为受控物质的治疗方法。在2020年10月13日新增第二项适应症，用于治疗成人猝倒症的发作性睡病。Wakix是一种选择性H3受体拮抗剂/反向激动剂。3Alnylam基本信息：重点品种Amvuttra在2023年的净销售额为5.58亿美元，该司2023年产品净销售额为12.41亿美元，最新市值为184.52亿美元。Amvuttra：在2022年6月13日获得FDA批准，成为当时第一个也是唯一一个，每三个月一次皮下注射可逆转神经病变损伤的疗法，用于治疗成人hATTR淀粉样变性多发性神经病。Amvuttra是一种siRNA，靶向突变型和野生型TTR的mRNA。4BioMarin基本信息：重点品种Voxzogo在2023年的净销售额为4.70亿美元，该司2023年总营收为24.19亿美元，最新市值为160.62亿美元。Voxzogo：在2021年8月27日获得欧盟批准，成为当时欧洲第一个治疗儿童软骨发育不全的药物。Voxzogo是一种修饰的C型利钠肽，通过下调FGFR3信号转导，从而促进软骨内骨形成。5Intra-Cellular Therapies基本信息：重点品种Caplyta在2023年的净销售额为4.62亿美元，该司2023年产品净销售额为4.62亿美元，最新市值为66.82亿美元。Caplyta：在2019年12月23日获得FDA批准，作为一种新型抗精神病药物，用于治疗成人精神分裂症。2021年12月17日新增适应症，成为唯一一种治疗成人I型或II型双相情感障碍（双向抑郁症）相关抑郁发作的药物，可作为单一疗法以及锂或丙戊酸的辅助疗法。Caplyta可能的作用机制为中枢血清素5-HT2A受体的拮抗剂和中枢突触后多巴胺D2受体的拮抗剂。6Sarepta Therapeutics基本信息：重点品种ELEVIDYS在2023年（只销售了2个季度）的净销售额为2.00亿美元，该司2023年产品净销售额为11.45亿美元，最新市值为119.7亿美元。ELEVIDYS：在2023年6月22日获得FDA批准，成为当时第一个也是唯一一个用于治疗杜氏肌营养不良症（DMD）的基因疗法。ELEVIDYS是一种基于AAV的基因疗法。7爵士制药基本信息：重点品种Xywav在2023年的净销售额为12.73亿美元，该司2023年产品净销售额为37.37亿美元，最新市值为75.94亿美元。Xywav：在2020年7月21日获得FDA批准，迎来当时近15年来治疗EDS/猝倒症的发作性睡病的第一个新治疗方案。2021年8月12日新增适应症，成为当时第一个也是唯一一个治疗特发性嗜睡症（IH）的药物。Xywav是一种含有羟丁酸钙、镁、钾和钠的口服溶液，受美国DEA管制。 8Immunocore基本信息：重点品种Kimmtrak在2023年的净销售额为2.39亿美元，该司2023年产品净销售额为2.39亿美元，最新市值为31.64亿美元。Kimmtrak：在2022年1月25日获得FDA批准，成为当时第一个也是唯一一个治疗不可切除或转移性葡萄膜黑色素瘤（mUM）的疗法，是第一个获批的TCR疗法，是第一个获批治疗实体瘤的T细胞衔接器。IMCgp100-202试验结果发表在《新英格兰医学杂志》上。Kimmtrak是一种双特异性蛋白，由抗CD3效应子融合TCR（针对gp100）组成。更多优质内容，欢迎关注↓↓↓

并购siRNA信使RNA上市批准

2024-03-17

·动脉网

激进基金巨头豪掷10亿美元，百傲万里因何成为热门标的？

2023年11月，全球最大激进对冲基金之一的Elliott investment Management（以下简称为Elliott）向生物技术公司BioMarin Pharmaceutical（百傲万里，以下简称BioMarin）注资超10亿美元，双方签订了合作与信息共享协议。路透社报道发布当天，公司股价上涨了约12%。BioMarin成立于1997年，总部位于美国加利福尼亚州，是一家开发针对罕见疾病治疗方法的生物制药公司。1999年7月在纳斯达克上市，成功完成IPO，共获6730万美元。而就在获Elliott投资当月，BioMarin刚刚宣布任命罗氏旗下基因泰克前CEO Alexander Hardy为公司新CEO。RBC Capital Markets的分析师Luca Issi认为，从BioMarin的业务执行情况而言，该笔大额投资的获得可被预估，但选取在新CEO刚刚上任的投资时间节点出乎意料。自2013年GEN编制生物制药领域TOP10并购名单起，BioMarin就连续霸榜。Fiercebiotech发布了“2022年生物制药领域可能被并购的TOP10目标名单”，BioMarin也位列其中。Biomarin还曾与罗氏、安进、吉利德等生物医药巨头传出“绯闻”，是名副其实的十大热门标的之一。具超30年从业经验，基因泰克前CEO就任BioMarin原CEO JJ Bienaimé在任职18年后退休卸任。新任CEO Alexander本科毕业于剑桥大学，具有密歇根大学罗斯商学院的工商管理硕士学位。同时，他也是美国药品研究与制造商协会（PhRMA）董事会成员。在医疗和生物技术行业，Alexander拥有30多年的从业经验，其中包括在基因泰克和罗氏工作的近20年。自2019年起，Alexander担任罗氏集团旗下基因泰克公司首席执行官。在这一“寒冬”时期，他参与了10种创新药物的成功上市，并带领公司在肿瘤学、神经科学、血友病和眼科等多个治疗领域取得了突破进展。在此之前，Alexander在罗氏和基因泰克也担任要职，包括全球产品战略负责人、亚太区负责人和后期产品组合委员会联合主席等，主要负责动态调整处于后期开发阶段的产品的开发战略，以及就内外部候选分子与研究和合作机构进行沟通。在加入基因泰克和罗氏之前，他还曾任职于诺华、Patho Genesis和葛兰素史克。Alexander Hardy（图源：BioMarin官网）Alexander在任职时提到，他能够看到BioMarin 的巨大潜力，对未来ROCTAVIAN™、VOXZOGO®等产品组合及其背后早期药物管线价值的释放十分有信心。2023财年总收入近25亿美元，第四季度收入同比增长20%除去Alexander加入的可能性因素，公司的财务状况无疑是吸引Elliott入股的重要决定因素。根据BioMarin的财务数据显示，2023年公司总收入为24.2亿美元（年同比增长15%，按固定汇率计算年同比增长20%），预计2024年总收入将实现两位数增长。图源：BioMarin官网具体分析，2023年第四季度的总收入为6.462亿美元，与2022年同期相比增长了20%。图源：BioMarin官网总收入的增长主要归因于软骨发育不全药物VOXZOGO®的销售量的增长。因为在美国食品和药物管理局（FDA）10月份批准VOXZOGO®用于所有年龄段的生长板开放儿童治疗后，5岁以下美国儿童的处方量增加。销售额增长的另一个原因是VIMIZIM®产品收入增加（政府大额订单），但由于失去市场独占权，仿制药竞争激烈，KUVAN®产品收入减少，故部分抵消了这一增长。也正是仿制药原因，公司在2022年6月与国家卫健委进行沟通，不再就KUVAN®（商品名“科望”）进口药品注册证进行再注册。据NMPA官网数据，科望的药品注册证书于2023年3月31日过期。与2022年同期相比，2023年第四季度的GAAP净收入增加了20万美元，达到2040万美元。图源：BioMarin官网净利润增加的主要原因是收入增加，以及公司在2022年第四季度宣布的组织重新设计相关的遣散费用的减少。但由于支持早期研究和临床活动的研发（R&D）项目支出增加，资产减值费用、公司治理和领导层过渡费用、支持ROCTAVIAN™商业化推出的费用有关的销售和行政（SG&A）费用增加等，部分抵消了上述增长。近20条药物管线，罕见病领域上市8款产品在研管线的规模是衡量创新药企发展趋势的重要指标，而研发药物产品的市场空间为公司收入增长提供路径。BioMarin在肌肉骨骼与代谢、非肿瘤血液学、心血管和中枢神经系统等治疗领域广泛布局，具有近20条药物管线。 BioMarin药物管线图（图源：BioMarin官网）除在分析财报时提到的BioMarin的部分产品外，在成立至今的超25年里，公司专注于罕见病领域共上市了8款产品，分别是ROCTAVIAN™、VOXZOGO®、PALYNZIQ®、BRINEURA®、VIMIZIM®、KUVAN®、NAGLAZYME®和ALDURAZYME®。以下，将重点介绍前两个产品。· ROCTAVIAN™（valoctocogene roxaparvovec-rvox）ROCTAVIAN™是一种基因疗法，适用于治疗经FDA批准的测试检测出无腺相关病毒血清型5(AAV5)抗体的重度A型血友病成人患者（先天性因子VIII(FVIII)缺乏症，FVIII活性小于1IU/dL）。ROCTAVIAN™使用AAV5病毒载体（经改良不含病毒DNA)递送表达凝血因子VIII。 ROCTAVIAN™（图源：BioMarin官网）血友病是一种由基因突变导致的遗传性疾病，目前的治疗方法主要是注射重组或血源性凝血因子制剂。但终身治疗的成本极大，且可能会产生抗体，阻碍治疗的有效性。而基因疗法则不同，它能够取代突变基因的功能，使严重A型血友病患者能够自己产生FVIII，帮助血液凝固，从源头上预防或减少出血的发生。患者可能只需要接受一次治疗，肝细胞就可以持续表达凝血因子VIII，从而不再需要长期接受预防性凝血因子注射。2022年8月欧盟委员会（EC）批准了BioMarin的A型血友病革命性疗法ROCTAVIAN™上市，这也是全球首个A型血友病基因疗法。2023年6月，ROCTAVIAN™获得FDA批准上市。· VOXZOGO®VOXZOGO®是首个也是唯一一个获准用于提高软骨发育不全和生长板开放儿童线性生长的疗法，是一种每天注射一次的C型钠尿肽（CNP）类似物。使用VOXZOGO®的儿童需要定期接受检查，根据身体发育情况调整剂量，在确认其不再有生长潜力、生长板闭合时停止使用。 VOXZOGO®（图源：BioMarin官网）2021年8月，VOXZOGO®获准在欧盟上市，用于两岁及以上患有开放性生长板软骨发育不全的患者。同年11月，FDA加速批准了VOXZOGO®在美国用于5岁及以上患有开放生长板的软骨发育不全患者，并授予BioMarin与VOXZOGO®的加速批准有关的罕见儿科疾病优先审查凭证（PRV），以表彰该公司在罕见病新药研发方面做出的突出贡献。2023年10月，FDA批准VOXZOGO®注射剂的补充新药申请(sNDA），将适应症扩大至所有年龄的开放生长板的儿童。在美国和欧盟，VOXZOGO®均被授予了治疗软骨发育不全症的孤儿药资格（ODD）。VOXZOGO®的2022年预计销售额为0.9-1.15亿美元，而实际销售额达到1.691亿美元；VOXZOGO®的2023年预计销售额为3.3-3.8亿美元，2023年的最终销售额达4.7亿美元，远超预计销售额，并且出现了由于需求大增而产能不足的情况。BioMarin无疑具有开发First in class及Best in class自研管线的能力和优势。BioMarin总裁兼首席执行官Alexander Hardy表示，2024年公司打算利用VOXZOGO®的机会，继续为ROCTAVIAN™建立全球准入渠道，审慎地优先考虑最具潜在影响力的研发候选项目。2021年12月，我国生物技术新锐九天生物与BioMarin达成合作，共同研究和开发基于腺相关病毒(AAV)的新型基因疗法用于治疗遗传性心血管疾病。九天生物作为在基因治疗领域尤其是新型病毒载体的“领头羊”，具有全方位整合的AAV基因治疗研发与生产体系。“一劳永逸”的基因疗法更依赖CDMO不同于传统小分子和大分子药物，细胞和基因疗法（Cell and Gene Therapy,CGT）具有相对差异化的治疗思路。基因疗法被看作是一种“一劳永逸”的革命性疗法，主要应用于肿瘤及各种遗传性罕见病治疗领域。它在治疗成本和治疗效果上远超传统疗法，是生物医药领域最具前景的发展方向之一。根据ASGCT（美国基因与细胞治疗年会）的统计，截至2024年Q4，全球在研CGT管线达到3951个，呈逐季度上升趋势。在基因疗法、RNA疗法和细胞疗法中，基因疗法管线占比最大，高达53%。按类别划分的在研疗法图（图源：ASGCT官网）根据沙利文测算，全球CGT疗法的市场规模有望在2025年达到305.4亿美元，对应2020-2025年CAGR高达71.2%。2023年12月，FDA发布了题为《细胞和基因治疗产品效力保证》的指导草案，草案中也提到了CGT产品快速临床开发不断增长的趋势。CGT对患者方而言具有“药到病除”的优势，但对创新药企而言具有生产成本高、工艺流程复杂和制备周期长的劣势，因此CGT行业对CDMO的依赖程度较高。据J.P.Morgan统计，与传统生物制剂相比，CGT具有更高的外包渗透率（预计超过65%）。全球基因治疗领域的CDMO如下图。基因治疗CDMO产业图谱（数据来源：动脉橙产业智库）据动脉橙产业智库不完全统计，2009年-2023年，全球基因治疗领域一级市场共产生565笔融资交易，累计融资额约242.69亿美元。2023年，我国基因治疗药物研发领域的多个项目获大额融资，基因疗法的“魅力”已被发现，潜力尚待突破。基因治疗药物研发领域融资金额排名TOP5项目（图片来源：《2023创新药及供应链年度创新白皮书》）近期推荐声明：动脉网所刊载内容之知识产权为动脉网及相关权利人专属所有或持有。未经许可，禁止进行转载、摘编、复制及建立镜像等任何使用。动脉网，未来医疗服务平台

高管变更并购IPO财报

2024-03-12

·BioSpace

New Data to be Presented for BioMarin's VOXZOGO® (vosoritide) in Children with Hypochondroplasia and Achondroplasia at the American College of Medical Genetics and Genomics (ACMG) Annual Clinical Genetics Meeting

Investigator-Sponsored Phase 2 Study Demonstrated Positive Results for VOXZOGO in Children with Hypochondroplasia New Analyses Highlight VOXZOGO 7-year Data and Improvement on Quality of Life in Children with Achondroplasia SAN RAFAEL, Calif., March 12, 2024 /PRNewswire/ -- BioMarin Pharmaceutical Inc. (Nasdaq: BMRN) announced that positive early results from an investigator-sponsored Phase 2 study of VOXZOGO® (vosoritide) in children with hypochondroplasia, will be presented at the 2024 American College of Medical Genetics and Genomics (ACMG) Annual Clinical Genetics Meeting in Toronto, Canada, March 12-16, 2024. Researchers will also present data from Phase 2 and Phase 3 studies of the medicine in children with achondroplasia, including results that demonstrate VOXZOGO's positive impact on quality of life. Results in Hypochondroplasia Andrew Dauber, M.D., will present positive results from his investigator-sponsored Phase 2 study of VOXZOGO in children with hypochondroplasia. The annualized growth velocity (AGV) increased from 5.12 cm/year during the observation period to 6.93 cm/year during the treatment period (mean difference: 1.81 cm/year, p<0.0001). No new safety signals were reported. "We are encouraged by preliminary results from the first study evaluating VOXZOGO in children with hypochondroplasia, suggesting the medicine has the potential to impact growth outcomes for this group of patients," said Dr. Dauber, who is the lead study author and Chief of Endocrinology at Children's National Hospital in Washington, D.C. "There are currently no approved medicines for children with hypochondroplasia, so we look forward to gathering additional data to deepen our understanding of VOXZOGO in hypochondroplasia and other growth-related conditions." In late 2023, BioMarin launched the pivotal clinical trial program studying the safety and efficacy of VOXZOGO in children with hypochondroplasia. A multinational observational study in children with hypochondroplasia (111-902) is currently recruiting participants, and the company plans to enter the treatment phase (Phase 3 trial) later this year. New Data Highlights VOXZOGO Long-Term Efficacy, Safety and Quality of Life in Achondroplasia 7-year Phase 2 Results in Achondroplasia Data from two studies of VOXZOGO in children ≥5 years of age with achondroplasia demonstrated a sustained improvement in AGV for each year that the participants were treated. In the Phase 2 study with more than 7 years of follow up, the mean increase in growth across each year of age up to 16 years compared with untreated participants was 1.63 cm/year for boys and 1.33 cm/year for girls. Separate cross-sectional comparative analysis assessing increase in height over a 7-year period showed an additional height gain of 11.03 cm with use of VOXZOGO compared to matched untreated children over the same period. 4-year Phase 3 Results in Achondroplasia The same analyses were produced for the Phase 3 trial in which children with achondroplasia have a mean treatment follow-up of 4 years. The mean increase in growth across each year of age up to 17 years was 1.73 cm/year for boys and 1.46 cm/year for girls. A separate cross-sectional comparative analysis assessing increase in height over a 3-year period showed an additional height gain of 5.75 cm with use of VOXZOGO compared to matched untreated children over the same period. 3-year Phase 3 Quality of Life Results in Achondroplasia Results from a separate analysis of the Phase 3 study showed that VOXZOGO improved health-related quality of life (HRQoL) among children with achondroplasia, particularly those associated with physical activities. After 3 years, the mean increase in Quality of Life in Short Stature Youth (QoLISSY) physical domain score was 6.0 as reported by caregivers and 6.3 as reported by children. These improvements were even more pronounced in children who grew more (for those with ≥ 1 SD increase in height z-score, the mean increase in physical domain score was 11.4 as reported by caregivers and 8.5 as reported by children). "The clinical results at ACMG reinforce the long-term benefit we are seeing in children treated with VOXZOGO, with a meaningful median height gain of more than 11 cm in children with achondroplasia following 7 years of treatment," said Hank Fuchs, M.D., president of Worldwide Research and Development at BioMarin. "We are particularly encouraged by new data demonstrating the potential impact height gains from VOXZOGO can have on quality of life, an outcome of incredible importance for children and families impacted by achondroplasia." "Achondroplasia can have a negative effect on a child's quality of life, including physical, social and emotional aspects," said Melita Irving, M.D., study investigator and consultant clinical geneticist at Guy's and St. Thomas' NHS Foundation Trust in London. "Our studies showed that increasing height with long-term administration of VOXZOGO can result in meaningful improvements in quality-of-life measures for children with achondroplasia." BioMarin's full list of presentations at ACMG includes: BioMarin Poster Presentations Persistence of Growth-Promoting Effects in Children with Achondroplasia Up to 7 Years: Update from a Phase 2 Extension Study with Vosoritide Poster #: P144 Friday, March 15, 2024, 10:30 a.m. – 12 p.m. ET Persistent Growth-Promoting Effects of Vosoritide in Children with Achondroplasia for Up to 4 Years: Update from Phase 3 Extension Study Poster #: P139 Thursday, March 14, 2024, 10:30 a.m. – 12 p.m. ET Persistent Growth-Promoting Effects of Vosoritide in Children with Achondroplasia is Accompanied by Improvement in Physical Aspects of Quality of Life Poster #: P141 Thursday, March 14, 2024, 10:30 a.m. – 12 p.m. ET Persistence of Growth-Promoting Effects in Infants and Toddlers with Achondroplasia: Results from a Phase 2 Extension Study with Vosoritide Poster #: P131 Thursday, March 14, 2024, 10:30 a.m. – 12 p.m. ET Exploring the Landscape of Phenylketonuria Education and Learning Needs of Genetics Trainees Poster #: P049 Thursday, March 14, 2024, 10:30 a.m. – 12 p.m. ET Reduction of Blood Phenylalanine in Participants Enrolled in OPAL, an Observational Study, Mirror Findings from the U.S.-based PRISM Population Poster #: P034 Friday, March 15, 2024, 10:30 a.m. – 12 p.m. ET Investigator-Sponsored Oral Presentation Vosoritide Increases Growth Velocity in Hypochondroplasia: Phase 2 Trial Results Oral Session: O03 Thursday, March 14, 2024, 1:30 – 3 p.m. ET About VOXZOGO In children with achondroplasia, endochondral bone growth, an essential process by which bone tissue is created, is negatively regulated due to a gain of function mutation in FGFR3. VOXZOGO, a C-type natriuretic peptide (CNP) analog, acts as a positive regulator of the signaling pathway downstream of FGFR3 to promote endochondral bone growth. VOXZOGO is approved in the U.S. and indicated to increase linear growth in children with achondroplasia with open epiphyses. This indication is approved under accelerated approval based on an improvement in annualized growth velocity. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trial(s). To fulfill this post-marketing requirement, BioMarin intends to use the ongoing open-label extension studies compared to available natural history. Patient Support Accessing VOXZOGO To reach a BioMarin RareConnections® Case Manager, please call, toll-free, 1-833-VOXZOGO (1-833-869-9646) or e-mail VOXZOGOSupport@biomarin-rareconnections.com. For more information about VOXZOGO, please visit . For additional information regarding this product, please contact BioMarin Medical Information at medinfo@bmrn.com. About Achondroplasia Achondroplasia, the most common form of skeletal dysplasia leading to disproportionate short stature in humans, is characterized by slowing of endochondral ossification, which results in disproportionate short stature and disordered architecture in the long bones, spine, face, and base of the skull. This condition is caused by a change in the FGFR3 gene, a negative regulator of bone growth. More than 80% of children with achondroplasia have parents of average stature and have the condition as the result of a spontaneous gene mutation. The worldwide incidence rate of achondroplasia is about one in 25,000 live births. VOXZOGO is being tested in children whose growth plates are still "open," typically those under 18 years of age. Approximately 25% of people with achondroplasia fall into this category. VOXZOGO U.S. Important Safety Information What is VOXZOGO used for? VOXZOGO is a prescription medicine used to increase linear growth in children with achondroplasia and open growth plates (epiphyses). VOXZOGO is approved under accelerated approval based on an improvement in annualized growth velocity. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials. What is the most important safety information about VOXZOGO? VOXZOGO may cause serious side effects including a temporary decrease in blood pressure in some patients. To reduce the risk of a decrease in blood pressure and associated symptoms (dizziness, feeling tired, or nausea), patients should eat a meal and drink 8 to 10 ounces of fluid within 1 hour before receiving VOXZOGO. What are the most common side effects of VOXZOGO? The most common side effects of VOXZOGO include injection site reactions (including redness, itching, swelling, bruising, rash, hives, and injection site pain), high levels of blood alkaline phosphatase shown in blood tests, vomiting, joint pain, decreased blood pressure, and stomachache. These are not all the possible side effects of VOXZOGO. Ask your healthcare provider for medical advice about side effects, and about any side effects that bother the patient or that do not go away. How is VOXZOGO taken? VOXZOGO is taken daily as an injection given under the skin, administered by a caregiver after a healthcare provider determines the caregiver is able to administer VOXZOGO. Do not try to inject VOXZOGO until you have been shown the right way by your healthcare provider. VOXZOGO is supplied with Instructions for Use that describe the steps for preparing, injecting, and disposing VOXZOGO. Caregivers should review the Instructions for Use for guidance and any time they receive a refill of VOXZOGO in case any changes have been made. Inject VOXZOGO 1 time every day, at about the same time each day. If a dose of VOXZOGO is missed, it can be given within 12 hours from the missed dose. After 12 hours, skip the missed dose and administer the next daily dose as usual. The dose of VOXZOGO is based on body weight. Your healthcare provider will adjust the dose based on changes in weight following regular check-ups. Your healthcare provider will monitor the patient's growth and tell you when to stop taking VOXZOGO if they determine the patient is no longer able to grow. Stop administering VOXZOGO if instructed by your healthcare provider. What should you tell the doctor before or during taking VOXZOGO? Tell your doctor about all of the patient's medical conditions including If the patient has heart disease (cardiac or vascular disease), or if the patient is on blood pressure medicine (anti-hypertensive medicine). If the patient has kidney problems or renal impairment. If the patient is pregnant or plans to become pregnant. It is not known if VOXZOGO will harm the unborn baby. If the patient is breastfeeding or plans to breastfeed. It is not known if VOXZOGO passes into breast milk. Tell your doctor about all of the medicines the patient takes, including prescription and over-the-counter medicines, vitamins, and herbal supplements. You may report side effects to BioMarin at 1-866-906-6100. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit , or call 1-800-FDA-1088. Please see additional safety information in the full Prescribing Information and Patient Information. About BioMarin Founded in 1997, BioMarin is a global biotechnology company dedicated to transforming lives through genetic discovery. The company develops and commercializes targeted therapies that address the root cause of the genetic conditions. BioMarin's unparalleled research and development capabilities have resulted in eight transformational commercial therapies for patients with rare genetic disorders. The company's distinctive approach to drug discovery has produced a diverse pipeline of commercial, clinical, and pre-clinical candidates that address a significant unmet medical need, have well-understood biology, and provide an opportunity to be first-to-market or offer a substantial benefit over existing treatment options. For additional information, please visit . Forward-Looking Statements This press release contains forward-looking statements about the business prospects of BioMarin Pharmaceutical Inc. (BioMarin), including without limitation, statements about: data to be presented at the 2024 American College of Medical Genetics and Genomics Annual Clinical Genetics Meeting, including the six poster presentations and the investor-sponsored oral presentation; the development of BioMarin's VOXZOGO program generally; the potential benefits of VOXZOGO for children with achondroplasia, including the duration of such benefits, potential improvement in annualized growth velocity (AGV), and potential improvement in health-related quality of life; the potential efficacy of VOXZOGO for children with hypochondroplasia, including potential to impact growth outcomes; and the continued clinical development of VOXZOGO, including BioMarin's plans for launching the treatment phase of the Phase 3 trial studying the safety and efficacy of VOXZOGO in children with hypochondroplasia. These forward-looking statements are predictions and involve risks and uncertainties such that actual results may differ materially from these statements. These risks and uncertainties include, among others: results and timing of current and planned preclinical studies and clinical trials of VOXZOGO; any potential adverse events observed in the continuing monitoring of the patients in the clinical trials; the content and timing of decisions by the U.S. Food and Drug Administration, the European Medicines Agency, the European Commission and other regulatory authorities; and those factors detailed in BioMarin's filings with the Securities and Exchange Commission, including, without limitation, the factors contained under the caption "Risk Factors" in BioMarin's Annual Report on Form 10-K for the year ended December 31, 2023 as such factors may be updated by any subsequent reports. Stockholders are urged not to place undue reliance on forward-looking statements, which speak only as of the date hereof. BioMarin is under no obligation, and expressly disclaims any obligation to update or alter any forward-looking statement, whether as a result of new information, future events or otherwise. BioMarin® and VOXZOGO® are registered trademarks of BioMarin Pharmaceutical Inc. Company Codes: NASDAQ-NMS:BMRN

临床结果临床2期临床3期上市批准

100 项与伏索利肽相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11190	伏索利肽	-	DB11928

研发状态

适应症	最高研发状态	国家/地区	公司
软骨发育不全	批准上市	日本更多	BioMarin Pharmaceutical Japan K.K. 更多
特纳综合症	临床2期	美国更多	Children's National Research Institute 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


ESPE2022	临床2期	软骨发育不良	26	Vosoritide	構齋選觸憲淵鏇餘繭襯(鏇遞衊鬱鑰簾觸觸廠選) = 簾衊繭淵願遞鏇構廠網積顧遞艱廠築構廠獵衊 (餘鹹選餘網簾壓壓鏇糧, 6.8 ~ 8)	-	2022-09-15
NCT03989947 (Study 111-206, PRNewswire) 人工标引	临床2期	软骨发育不全	-	VOXZOGO	(齋構齋選鬱餘齋膚襯鬱) = 積構獵餘膚範蓋鏇衊願築壓淵襯顧醖衊廠鑰選 (鏇鏇遞遞範齋簾築襯選, 0.46-1.93) 更多	积极	2023-10-20
NCT03197766 (CTgov)	临床3期	软骨发育不全	121	Placebo	鑰積壓廠餘簾蓋遞積夢(夢鹽鏇鹹鏇鹹顧網鹹糧) = 願齋窪遞觸築獵襯艱遞膚鑰範廠夢齋簾繭鑰鏇 (製鬱鏇襯糧鹹壓蓋築夢, 築鏇築選築鑰蓋窪襯鏇 ~ 衊顧艱衊製壓廠齋鹽廠) 更多	-	2022-03-02
NCT03583697 (Corporate Publications) 人工标引	临床2期	软骨发育不全	75	vosoritide	(齋窪獵製夢襯鹽觸齋夢) = 鹽鹹襯襯獵鏇網鑰鑰觸鏇壓壓網糧範艱壓蓋鹽 (鏇衊鹹窪壓製淵夢廠遞, 0.07 - 0.54) 更多	积极	2022-06-13
NCT03583697 (Corporate Publications) 人工标引	临床2期	软骨发育不全	75	Placebo	(鑰範憲願窪齋齋獵繭鹽) = 壓鹽鹹鹽製築鏇憲遞蓋構鏇鏇繭鑰網齋選觸製 (夢鏇願膚顧蓋襯鏇鑰積 )	积极	2022-06-13
NCT03424018 (Pubmed \| Genet Med) 人工标引	临床3期	软骨发育不全	119	Vosoritide	構網遞築築蓋鑰選蓋積(襯鹽醖鏇積夢積鹽鹽醖) = 簾選醖觸淵窪願鹹憲構繭願窪選簾鹽糧壓襯蓋 (繭構醖鬱艱襯壓觸築壓 ) 更多	积极	2021-12-01
NCT03424018 (Pubmed \| Genet Med) 人工标引	临床3期	软骨发育不全	119	Placebo	構網遞築築蓋鑰選蓋積(襯鹽醖鏇積夢積鹽鹽醖) = 鏇製範憲製鬱糧範顧觸繭願窪選簾鹽糧壓襯蓋 (繭構醖鬱艱襯壓觸築壓 ) 更多	积极	2021-12-01
NCT03197766 (Pubmed) 人工标引	临床3期	软骨发育不全	121	vosoritide	(夢廠製窪廠鬱齋膚衊觸): difference = 1.57 (95% CI, 1.22 ~ 1.93) 更多	积极	2020-09-05
NCT03197766 (Pubmed) 人工标引	临床3期	软骨发育不全	121	Placebo	(夢廠製窪廠鬱齋膚衊觸): difference = 1.57 (95% CI, 1.22 ~ 1.93) 更多	积极	2020-09-05
ATU (ESPE2022)	N/A	软骨发育不全	29	Vosoritide	(憲願遞簾艱膚鹽醖製選) = The majority of AEs were mild and included injection site reactions and vomiting, with the most common being injection site rash (4 events) 膚獵襯壓窪夢膚糧製壓 (顧構憲醖襯淵鹽襯簾構 ) 更多	积极	2022-09-15
Phase 2 Clinical Trial (ESPE2018)	临床2期	软骨发育不全 FGFR3 \| C-type natriuretic peptide (CNP) \| urine cGMP	35	Vosoritide 2.5 μg/kg	憲顧願夢鏇鹽衊選繭製(憲衊製襯醖網衊築遞淵) = 憲鏇範觸夢膚範憲繭蓋膚夢淵窪遞膚鏇窪廠繭 (糧範膚網淵壓窪壓艱餘, 2.275)	积极	2018-09-27
Phase 2 Clinical Trial (ESPE2018)	临床2期		35	Vosoritide 15 μg/kg	憲顧願夢鏇鹽衊選繭製(憲衊製襯醖網衊築遞淵) = 範齋網構鹽壓鹹糧襯製膚夢淵窪遞膚鏇窪廠繭 (糧範膚網淵壓窪壓艱餘, 1.873)	积极	2018-09-27
111-208 (ESPE2023)	临床2期	软骨发育不全	34	Vosoritide 15 mg/kg	(艱鹹衊襯觸齋簾遞蓋範) = 鑰顧齋範艱網壓獵築顧積憲糧膚範憲簾製齋鹽 (壓膚醖願齋蓋鬱網製夢, 2.98 ~ 9.56)	积极	2023-09-21