COACH: A Phase 2, Open-Label, Single-Arm, 156-week Trial to Investigate the Efficacy, Safety and Tolerability of Combined Once Weekly Navepegritide and Lonapegsomatropin in Children with Achondroplasia - ASND0042

开始日期2024-07-26

申办/合作机构

Ascendis Pharma Growth Disorders A/S

NCT06433557 / Recruiting临床2期

A Phase 2, Open-Label, Single-Arm, 156-week Trial to Investigate the Efficacy, Safety and Tolerability of Combined Once Weekly Navepegritide and Lonapegsomatropin in Children With Achondroplasia

This proof-of-concept trial is being conducted to evaluate the efficacy, safety and tolerability of combination treatment with navepegritide and lonapegsomatropin administered as separate subcutaneous (SC) injections once weekly in children with achondroplasia (ACH) aged 2 to 11 years.

开始日期2024-07-26

申办/合作机构

Ascendis Pharma Growth Disorders A/S

NCT06079398 / Recruiting临床2期

A Phase 2, Multicenter, Double-Blind, Randomized, Placebo-controlled Trial, Evaluating Safety, Tolerability, and Efficacy of Subcutaneous Doses of TransCon CNP Administered Once Weekly for 52 Weeks in Infants (0 to <2 Years of Age) with Achondroplasia Followed by an Open Label Extension (OLE) Period

This trial is a Phase 2, multicenter, double-blind, randomized (ratio 2:1 TransCon CNP vs. placebo), placebo-controlled trial, designed to evaluate the safety, tolerability, and efficacy of 100 μg CNP/kg of Navepegritide (TransCon CNP) administered SC once-weekly for 52 weeks in infants with genetically verified heterozygous ACH, aged 0 to < 2 years at the time of randomization.

开始日期2024-01-23

申办/合作机构

Ascendis Pharma A/S

100 项与 Navepegritide 相关的临床结果

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100 项与 Navepegritide 相关的转化医学

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100 项与 Navepegritide 相关的专利（医药）

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项与 Navepegritide 相关的文献（医药）

2024-05-05·Cureus Journal of Medical Science

Two Cases of Cardiovascular Adverse Events Following Subcutaneous Vosoritide Injection in Early Infancy

Article

作者: Oda, Yoichiro ; Nishioka, Atsushi ; Adachi, Natsuho ; Tanaka, Hiroyuki

Achondroplasia, characterized by short stature and skeletal abnormalities, is caused by a gain-of-function variant in the fibroblast growth factor receptor 3 gene. Vosoritide, a C-type natriuretic peptide analog, is an emerging treatment for achondroplasia that functions by promoting endochondral ossification. Vosoritide was approved for the treatment of achondroplasia in Europe and the United States in 2021, and in Japan, the following year. However, vosoritide is associated with a risk of hypotension and vomiting after subcutaneous injection due to its vasodilating effect. Herein, we present two cases of cardiovascular adverse events in infants following vosoritide injection. Case 1 involved a one-month-old female infant with achondroplasia who received the first subcutaneous injection of vosoritide 30 minutes after her last formula intake. Following injection, she developed transient symptomatic hypotension accompanied by vomiting. Although established guidelines recommend that injections be administered after approximately 30 minutes (Europe/Japan) or within one hour (USA) following the last feeding, an extended interval of 1.5 to two hours was required to prevent hypotension-associated vomiting. Case 2 involved a three-month-old female infant with achondroplasia. The first subcutaneous vosoritide injection was administered four hours after the last formula intake, and she subsequently developed prolonged compensated shock with marked tachycardia requiring intervention, including repetitive bolus saline injection. These cases indicate the need to monitor patients for cardiovascular adverse events following subcutaneous injection of vosoritide in early infancy.

2024-05-01·EClinicalMedicine

Vosoritide treatment for children with hypochondroplasia: a phase 2 trial

Article

作者: Merchant, Nadia ; Castro, Meryll Grace ; Shafaei, Niusha ; Boucher, Kimberly ; Dauber, Andrew ; Zhang, Anqing ; Dham, Niti ; Seaforth, Raheem ; Kanakatti Shankar, Roopa ; McCarthy, Tara

Background:

Hypochondroplasia is a rare autosomal dominant skeletal dysplasia due to activating variants in FGFR3. It presents with disproportionate short stature with a wide range of clinical severity. There are currently no approved medications to treat short stature in children with hypochondroplasia. Vosoritide is a C-type natriuretic peptide analog that was recently approved for improving growth in children with achondroplasia. We aimed to evaluate the safety and efficacy of vosoritide in children with hypochondroplasia.

Methods:

We conducted a single-arm, phase 2, open-label trial at a single centre in the USA and enrolled 26 children with hypochondroplasia. The trial consists of a 6-month observation period to establish a baseline annualized growth velocity followed by a 12-month intervention period during which vosoritide is administered daily via subcutaneous injection at a dose of 15 μg/kg/day. The trial's co-primary endpoints included the incidence of adverse events and the change from baseline in age-sex standardized annualized growth velocity and height standardized deviation score (SDS) after 12 months of treatment. This trial is registered with ClinicalTrials.gov (NCT04219007).

Findings:

Twenty-four participants with a mean age of 5.86 years received vosoritide therapy. The first participant was enrolled on August 4, 2020, and the final participant completed the 18-month trial on September 8, 2023. Vosoritide was well tolerated with no treatment-related serious adverse events. Injection site reactions occurred in 83.3% of participants. No participants discontinued therapy due to an adverse event. Annualized growth velocity increased by 2.26 standard deviations (SD) and height SDS increased by 0.36 SD during the treatment period versus the observation period. Hypochondroplasia specific height SDS increased by 0.38 SD. There was a 1.81 cm/year increase in absolute annualized growth velocity.

Interpretation:

Vosoritide was safe and effective in increasing growth velocity in children with hypochondroplasia. Efficacy was similar to what has been reported in children with achondroplasia.

Funding:

This study was supported by an investigator-initiated grant from BioMarin Pharmaceutical.

2023-11-01·EClinicalMedicine

Once-weekly TransCon CNP (navepegritide) in children with achondroplasia (ACcomplisH): a phase 2, multicentre, randomised, double-blind, placebo-controlled, dose-escalation trial

Article

作者: Ma, Nina S ; Zarate, Yuri A ; Savarirayan, Ravi ; Winding, Bent ; Mao, Meng ; Sousa, Sérgio B ; Bober, Michael B ; McDonnell, Ciara ; Smith, Alden ; Legare, Janet M ; Hoernschemeyer, Daniel G ; Bacino, Carlos A ; Volck, Birgitte ; Schnabel, Dirk ; Chakraborty, Mukta ; Hofman, Paul L ; Ljungberg, Merete ; Giwa, Adebola ; White, Klane K ; Högler, Wolfgang ; Shu, Aimee D ; Quattrin, Teresa ; Abuzzahab, M Jennifer

Background:

TransCon CNP (navepegritide) is an investigational prodrug of C-type natriuretic peptide (CNP) designed to allow for continuous CNP exposure with once-weekly dosing. This 52-week phase 2 (ACcomplisH) trial assessed the safety and efficacy of TransCon CNP in children with achondroplasia.

Methods:

ACcomplisH is a global, randomised, double-blind, placebo-controlled, dose-escalation trial. Study participants were recruited between June 10, 2020, and September 24, 2021. Eligible participants were prepubertal, aged 2-10 years, with genetically confirmed achondroplasia, and randomised 3:1 to once-weekly subcutaneous injections of TransCon CNP (6, 20, 50, or 100 μg CNP/kg/week) or placebo for 52 weeks. Primary objectives were safety and annualised growth velocity (AGV). ACcomplisH is registered with ClinicalTrials.gov (NCT04085523) and Eudra (CT 2019-002754-22).

Findings:

Forty-two participants received TransCon CNP at doses of 6 μg (n = 10; 7 female), 20 μg (n = 11; 3 female), 50 μg (n = 10; 3 female), or 100 μg (n = 11; 6 female) CNP/kg/week, with 15 receiving placebo (5 female). Treatment-emergent adverse events (TEAEs) were mild or moderate with no grade 3/4 events reported. There were 2 serious TEAEs that were assessed as not related to TransCon CNP. Eleven injection site reactions occurred in 8 participants receiving TransCon CNP and no symptomatic hypotension occurred. TransCon CNP demonstrated a dose-dependent improvement in AGV. At 52 weeks, TransCon CNP 100 μg CNP/kg/week significantly improved AGV vs placebo (least squares mean [95% CI] 5.42 [4.74-6.11] vs 4.35 [3.75-4.94] cm/year; p = 0.0218), and improved achondroplasia-specific height SDS from baseline (least squares mean [95% CI] 0.22 [0.02-0·41] vs -0·08 [-0.25 to 0.10]; p = 0.0283). All participants completed the randomised period and continued in the ongoing open-label extension period receiving TransCon CNP 100 μg CNP/kg/week.

Interpretation:

This phase 2 trial suggests that TransCon CNP is effective, safe, with low injection site reaction frequency, and may provide a novel, once-weekly treatment option for children with achondroplasia. These results support TransCon CNP at 100 μg CNP/kg/week in the ongoing pivotal trial.

Funding:

Ascendis Pharma, A/S.

项与 Navepegritide 相关的新闻（医药）

2024-10-30

·BioSpace

BioMarin Surpasses Analysts’ Q3 Sales Estimates Despite Voxzogo’s Slight Miss

Pictured: BioMarin headquarters in California/iSto iStock , Sundry Photography The biotech beat Wall Street’s third-quarter revenue forecast by 6%, driven by increased uptake of its achondroplasia drug Voxzogo. However, William Blair downgraded BioMarin’s shares to market perform due to a “lack of near-term catalysts” and uncertainty around Voxzogo’s potential revenue growth. BioMarin Pharmaceuticals on Tuesday announced $746 million in total revenue in the third quarter , 28% year-over-year growth driven by the continued strong uptake of its therapies for rare genetic diseases. The biotech beat consensus estimates, surpassing Wall Street’s expected Q3 revenue of $703 million by 6%. BMO Capital Markets analyst Kostas Biliouris in an investor note attributed BioMarin’s strong performance to the continued growth of its achondroplasia medicine Voxzogo, with sales of $190 million jumping 54%. There are now over 3,800 patients on Voxzogo, according to BioMarin, up from around 3,500 in the second quarter . Still, Wall Street anticipated Voxzogo generating $195 million for BioMarin in Q3, a bar the company missed by 3%. Roctavian, a gene therapy approved in June 2023 for hemophilia A , brought in $7 million in the quarter, in line with the analyst consensus. And while its relative contribution to BioMarin’s total Q3 revenue is low, Roctavian presents a high-growth opportunity for the biotech with 600% sales growth versus the same period the year prior. Biliouris said that this “continued uptake” of Roctavian reflects the company’s efforts to focus on the U.S., Italy and Germany markets, potentially paving the way for hitting around $60 million in revenue for the gene therapy by 2025. Truist Securities analyst Joon Lee also credited BioMarin’s Sanofi-partnered enzyme replacement therapy Aldurazyme for its Q3 beat. Sales of Aldurazyme, indicated for mucopolysaccharidosis I, jumped 407% in the quarter bringing in $71 million and beating the consensus expectation of $30 million by $137%. Encouraged by its strong Q3 showing—and by the continued growth of its products—BioMarin on Tuesday raised its full-year 2024 revenue guidance to between $2.79 billion and $2.825 billion. The biotech previously expected a range of $2.75 billion to $2.825 billion this year. Despite BioMarin’s promising outlook for 2024, Lee warned about impending competitive pressure on Voxzogo. Last month, Ascendis Pharma revealed strong pivotal data for its investigational drug TransCon CNP, also known as navepegritide, which showed significant improvements in annual growth velocity in children with achondroplasia. Ascendis is gearing up for a regulatory filing for TransCon CNP in the first quarter of 2025. “In light of better-than-expected data, we’re left to wonder what further impact competition from TransCon-CNP may have on BioMarin’s mid- to long-term guidance,” Lee said. Likewise, William Blair analyst Sami Corwin in a note to investors said that despite the Q3 beat, her firm downgraded shares of BioMarin to market perform. “We do not think its clinical pipeline will be a source of significant value creation in the near term,” according to Corwin. “Voxzogo remains the key top-line growth driver for the company, but the threat of competition could erode its revenue growth and market share.”

上市批准

2024-10-24

·CPHI制药在线

罕见病ACH“救命药”关键实验达主要终点，每年长高6厘米！

关注并星标CPHI制药在线近日，Ascendis Pharma 披露了其在研疗法 TransCon CNP（navepegritide）于 ApproaCH 试验中的积极顶线数据情况。研究分析表明，该试验达成了主要终点，与安慰剂相比，TransCon CNP 显著提高了软骨发育不全儿童（年龄处于2 至11岁）患者的年化生长速度（AGV）。那韦培肽（navepegritide）属于一款长效的C 型利钠肽前药，被用于软骨发育不全的治疗。并且，此药已同时被美国食品和药品监督管理局以及欧盟委员会认定为孤儿药。软骨发育不全属于人类最为常见的矮小症，是由编码成纤维细胞生长因子受体3(FGFR3)基因当中的一种常见致病突变所引发，这种突变会给骨骼生长的软骨内骨化过程带来影响。针对软骨发育不全发病机制的治疗手段始终是一项重大却尚未被满足的需求。针对 FGFR3基因变异的药物，当下仅有一款 CNP药物，即伏索利肽（Vosoritide)。C型利钠肽(CNP)在人体里自然存在，是骨骼生长的正向调控因子，是有效的软骨内骨化刺激物，能够和特定的受体相结合，启动能抑制过度活跃的 FGFR3通路的细胞内信号，进而阻止 FGFR3对软骨细胞造成干扰。一、软骨发育不全（ACH）-先天性遗传性罕见骨病骨发育不良属于先天性、遗传性的罕见病症，会对骨与软骨的组织结构及发育形成影响，为常染色体显性遗传病症。其在人群中的发病几率大概在 1/5000 至100,000之间，涵盖了与数以百计遗传缺陷相关的各种不同类型的骨和软骨发育不良，在临床上呈现的表型有差异，软骨发育不全（ACH）属于最为常见的类型，此外还包含假性软骨发育不良、多发骨骺发育不良（MED）、脊椎骨骺发育不良（SED）等等，其中的绝大多数已被全球范围内纳入罕见病的目录之中。软骨发育不全（ACH）大概每17,000 至28,000名的活产婴儿中会有1 名出现（其中约20%是由父母遗传），我国的儿童软骨发育不全患儿大概有10000 人上下。儿童软骨发育不全也被称作胎儿型软骨营养障碍、软骨营养障碍性侏儒等，属于由于软骨内骨化存在缺陷所致的先天性发育异常情况，是一种儿童罕见病。软骨发育不全由成纤维细胞生长因子受体3(FGFR3)基因的功能增益突变所引发，属于常染色体显性遗传。FGFR3及其抑制性下游信号通路的激活会致使软骨内骨化的速度减缓。几乎所有软骨发育不全患者的 FGFR3 跨膜编码区均存在1138G→A(Gly380Arg)或者1138G→C(Gly380Arg)的致病突变。在过去的 20 年当中，针对这些致病突变下游通路的界定和认知为靶向治疗提供了基础。该疾病的特征为头部明显较大（大头畸形）、上臂较短（根状侏儒症）以及身材矮矮小小（女性的最终成人身高通常处于124cm 之间，男性则在132cm之间）。软骨发育不全通常不会致使智力受到损伤，倘若连接头颈部的骨头未对脑干或者上脊髓形成压迫，那么预期寿命和正常人接近。软骨发育不全的最优治疗时机应当在生长板闭合之前进行用药，一旦错过这一生长发育的黄金时期，药物所能起到的帮助将会十分有限。二、ApproaCH试验鉴于CNP类似物在治疗软骨发育不全方面存在希望，Ascendis Pharma研发出了一种具有缓释且长效特性的 CNP（那韦培肽），期望能够为生长板提供更为平稳的CNP 水平。为此，他们把 CNP 和一种无活性的载体分子相联结，让 CNP避免被清除，并且有望延长其对于生长板发挥的作用。在完成动物机制验证研究之后，又在健康的成年男性中开展了 1期研究，结果表明这种长效的CNP 具备良好的耐受性，药代动力学特点契合每周给药一次的需求。此次所公布的ApproaCH试验属于一项关键的双盲安慰剂对照试验，总计有 84名罹患软骨发育不全的儿童（年龄处于2 - 11 岁）参与进来，按照2 ：1 的比例被随机分配为接受每周一次的TransCon CNP或者安慰剂治疗。分析表明，试验达成了主要终点。在第52周的时候，接受TransCon CNP治疗的儿童（n =57）的最小二乘（LS）平均 AGV 为5.89厘米/年，然而安慰剂组（n =27）患者的 LS 平均AGV 为4.41 厘米/年，两组之间的 LS 平均差异是 1.49厘米/年（p<0.0001）。进一步开展的亚组分析指出，接受TransCon CNP治疗的2 至5 岁儿童（n =21）在第 52周时的LS 平均 AGV 为6.07厘米/年，而安慰剂组（n =10）的LS 平均 AGV 为5.06厘米/年，LS 平均差异为 1.02厘米/年（p = 0.0084）。接受TransCon CNP治疗的5 - 11 岁儿童（n =36）在第 52周时的LS 平均 AGV 为5.79厘米/年，而安慰剂组（n =17）的LS 平均 AGV 为4.02厘米/年，LS 平均差异为 1.78厘米/年（p<0.0001）。 TransCon CNP一直保持着与安慰剂相似的安全性，并且总体耐受性优良，治疗过程中出现的不良事件（TEAE）大多数都是轻度的。 TransCon CNP属于一种处于研究阶段的 C型利钠肽（CNP）前体药物，每周给药一次，旨在给予患者活性CNP 的持续暴露。C型利钠肽能够通过阻挡 FGFR3 的活性，仿若松开抑制儿童生长的“刹车”。直接靶向软骨发育不全的潜在病理生理学，从而促进软骨内骨形成，让患儿的生长速率恢复正常。三、其他临床疗法伏索利肽（Vosoritide) 欧洲药品管理局（EMA）在2021 年准许伏索利肽对 2岁及以上的软骨发育不全患儿（直至生长板闭合）展开治疗。基于针对3 个月至5 岁软骨发育不全患儿临床试验所有数据集合的评价，美国FDA 在 2023年 10月许可伏索利肽用于治疗全部生长板开启的软骨发育不全患儿（也就是从出生起始）。伏索利肽已经在46 个国家被批准用以治疗软骨发育不全儿童，于日本和澳大利亚，从出生到生长板闭合的这段时期都能够加以运用。在II期临床探究中，经过 60个月的治疗，年化生长速度（AGV）提升了 1.35厘米/年，治疗 60个月时身高增加了 9.08厘米；在III期临床研究里，治疗 1年时年化生长速度（AGV）改良了1.57厘米/年，治疗 1年时身高增进了 0.28；最新的II期临床研究显示，观察到 3 -59个月年龄的患者接受 52周的治疗，除去身高的改变，身体比例、颅骨以及脑形态（涵盖枕骨大孔、脑室和脑实质的尺寸）的变动较为显著。伏索利肽（Vosoritide)具备良好的耐受性，副作用发生的几率不存在明显差异，5 岁以下和较大年龄的患者在安全性方面相近，III期临床研究未上报与治疗有关的严重不良情况。英菲格拉替尼(Infigratinib) 英菲格拉替尼属于一种口服型且具备生物可利用性的 FGFR1 -3 选择性的抑制剂，在针对由 FGFR2突变所驱使的曾经接受过治疗或者转移性的肝内胆管癌的治疗中呈现出良好前景。鉴于这些数据以及英菲格拉替尼对软骨发育不全小鼠模型的骨表型（涵盖枕骨大孔和骨性椎管的尺寸）所发挥的改善作用，针对软骨发育不全儿童（年龄处于2.5- 16岁）的观察性生长与干预的临床试验已然开启，以此对该种口服疗法的安全性与有效性展开评估（PROPEL[NCT04035811]以及 PROPEL - 2[NCT04265651]）。2 期的剂量探寻研究（PROPEL- 2）表明，处于最高剂量组的英菲格拉替尼（0.25mg/kg/d）的患儿未曾出现和治疗相关的不良事件，并且相较于之前的观察性研究中的基线生长速度，平均每年能够多长3cm。这些数据相当振奋人心，特别是鉴于这种药物为口服的小药片，能够撒在幼儿的食物之中。一项重要的 3期试验已于2023 年12 月启动（NCT06164951）。瑞夫明西普(Recifercept) 一种具备配体捕获作用的可溶性FGFR3分子（瑞夫明西普），能够优化软骨发育不全小鼠模型的骨表型。基于这一数据，Therachon Pharma 公司与辉瑞公司接连开发了此类潜在疗法，并针对0-10 岁的软骨发育不全儿童实施了观察性和干预性临床试验（NCT03794609以及 NCT04638153）。在 2022年，鉴于随机分配接受瑞夫明西普治疗的儿童相较安慰剂儿童来说，年生长速度没有上升，这些试验因疗效欠佳而被终止。 SAR-442501 2021 年，一种针对 FGFR3 的人单克隆抗体（SAR-442501）获取了欧洲医学管理局（EMA）所授予的孤儿药认定，目的是用于医治软骨发育不全的儿童。赛诺菲展开了一项观察研究，针对 0至 10岁软骨发育不全儿童实施纵向生长的测量数据收集工作，并对数字生物标志物（像是家庭睡眠监测仪器以及监控体力活动的可穿戴设备）的运用状况予以评估，以此当作该 FGFR3 抗体化合物 2期干预试验的序曲。到了2023 年10 月，SAR-442501 的开放标签2 期研究在 0至 12 岁的软骨发育不全儿童当中开启，每周进行两次皮下注射（NCT06067425）。美克洛嗪(Meclizine) 美克洛嗪是一种现成的非处方口服抗组胺药，常用于治疗晕车，被认为是治疗软骨发育不全症的潜在方法，可促进软骨发育不全小鼠模型的纵向骨生长。这一发现促成了一项1a期试验，在12名5-11岁软骨发育不全日本儿童中每天给予一次或两次美克洛嗪，从而获取药代动力学数据。美克洛嗪的耐受性良好，没有出现严重的不良反应。 RBM-007 RBM-007 属于一种 RNA 适配体，能够和FGF2实现特异性结合，进而阻挡其与FGFR3相互接触。相关研究指出，RBM-007 能够挽回野生型小鼠胫骨里的 FGFR3 信号，让软骨发育不全患者诱导多能干细胞中的软骨细胞分化得以恢复，也能够让软骨发育不全小鼠模型里的非正常生长回归正常化。基于此，提出了它或许能有效治疗软骨发育不全的这一假设。当前，RBM-007 在日本正处于早期临床研发的阶段。四、展望在过去的十年期间，首个用于软骨发育不全儿童的精准疗法（伏索利肽）已得到批准，同时其他具有潜力的疗法也在临床研发的进程之中。接下来的十年，不但要明确哪些药物对于改善软骨发育不全的并发症效果最为显著，而且还得进一步明确这些新疗法的利弊得失。能够促进软骨发育不全婴儿颅面部骨骼非正常发育改善以及颅底孔（特别是枕骨大孔）生长的药物将会具有关键的潜在临床价值。长期的临床研究将会查明这些改善有无降低婴儿猝死、睡眠呼吸障碍的出现概率，还有减压和颅颌面手术的必要程度。未来的试验还会评判这些疗法的最佳起始时刻和剂量，以及是否能够联合运用来增强治疗效果。既然这些疗法是由制药公司研制开发的，所以一定要保证软骨发育不全患儿在全球范围之内都能够平等地获取这些疗法。此项工作需要国际方面以及政府与制药公司相互合作，同时也离不开软骨发育不全患者及其家人和支持组织的倡议与主动参与。不管是当下还是未来，都会存在软骨发育不全患者以及他们的家人选择不去运用这些新药物，特别是倘若新药的主要作用是增多线性生长，就像临床试验的主要终点所体现的那样。针对这些人而言，身材娇小是其内在个人身份的一个重要构成部分，而并非是需要变更的特质——这类观点必须予以尊重。想要清楚这些新药是否还会改变软骨发育不全相关的基线发病概率和死亡概率，仍然需要长期的观察资料。这些新疗法永远没办法替代针对软骨发育不全患者及其家庭的全生命周期看护、宣扬、社区教育和政策扶持。参考资料： [1] Pivotal ApproaCH Trial of TransCon™ CNP (Navepegritide) Achieved Primary Objective, Demonstrated AGV Superior to Placebo. Retrieved September 17, 2024 from https://investors.ascendispharma.com/news-releases/news-release-details/pivotal-approach-trial-transcontm-cnp-navepegritide-achieved END 来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com ▼更多制药资讯，请关注CPHI制药在线▼ 点击阅读原文，进入智药研习社~

孤儿药

2024-09-17

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每年长高6厘米！创新疗法关键试验达主要终点

▎药明康德内容团队编辑日前，Ascendis Pharma公布其在研疗法TransCon CNP（navepegritide）在ApproaCH试验的积极顶线数据。分析显示，试验达成主要终点，TransCon CNP相较于安慰剂显著增加软骨发育不全儿童（年龄2-11岁）患者的年化生长速度（AGV）。软骨发育不全主要表现为四肢、脊柱和头骨底部的骨骼生长缓慢。它的发病原因是由于编码成纤维细胞生长因子受体3（FGFR3）的基因出现突变，导致FGFR3蛋白过度活跃。FGFR3是骨骼发育的负向调节分子，可影响软骨细胞的增殖、活化和分化。这次所公布的ApproaCH试验是一项关键双盲安慰剂对照试验，共有84名患有软骨发育不全的儿童（年龄2-11岁）入组，以2：1的比例随机分配接受每周一次TransCon CNP或安慰剂治疗。分析显示，试验达成主要终点。在第52周时，接受TransCon CNP治疗儿童（n=57）的最小二乘（LS）平均AGV为5.89厘米/年，而安慰剂组（n=27）患者的LS平均AGV为4.41厘米/年，两组间的LS平均差异为1.49厘米/年（p<0.0001）。进一步的亚组分析显示，接受TransCon CNP治疗的2至5岁儿童（n=21）在第52周时的LS平均AGV为6.07厘米/年，而安慰剂组（n=10）的LS平均AGV为5.06厘米/年，LS平均差异为1.02厘米/年（p=0.0084）。接受TransCon CNP治疗的5-11岁儿童（n=36）在第52周时的LS平均AGV为5.79厘米/年，而安慰剂组（n=17）的LS平均AGV为4.02厘米/年，LS平均差异为1.78厘米/年（p<0.0001）。 TransCon CNP持续表现出与安慰剂相当的安全性，且总体耐受性良好，治疗中出现的不良事件（TEAE）大多为轻度。图片来源：123RF TransCon CNP是一种在研C型利钠肽（CNP）前体药物，每周给药一次，旨在提供患者活性CNP的持续暴露。C型利钠肽可通过阻断FGFR3的活性，就好像松开抑制儿童生长的“刹车”，直接靶向软骨发育不全的潜在病理生理学，从而促进软骨内骨形成，让患儿的生长速率恢复正常。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料： [1] Pivotal ApproaCH Trial of TransCon™ CNP (Navepegritide) Achieved Primary Objective, Demonstrated AGV Superior to Placebo. Retrieved September 17, 2024 from https://investors.ascendispharma.com/news-releases/news-release-details/pivotal-approach-trial-transcontm-cnp-navepegritide-achieved 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

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适应症	最高研发状态	国家/地区	公司	日期
软骨发育不全	临床3期	美国	Ascendis Pharma Growth Disorders A/S	2023-03-03
软骨发育不全	临床3期	澳大利亚	Ascendis Pharma Growth Disorders A/S	2023-03-03
软骨发育不全	临床3期	加拿大	Ascendis Pharma Growth Disorders A/S	2023-03-03
软骨发育不全	临床3期	丹麦	Ascendis Pharma Growth Disorders A/S	2023-03-03
软骨发育不全	临床3期	爱尔兰	Ascendis Pharma Growth Disorders A/S	2023-03-03
软骨发育不全	临床3期	新西兰	Ascendis Pharma Growth Disorders A/S	2023-03-03
软骨发育不全	临床3期	西班牙	Ascendis Pharma Growth Disorders A/S	2023-03-03

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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


NCT05598320 (ApproaCH, PipelineReview) 人工标引	临床2/3期	软骨发育不全	84	TransCon CNP (ages 2-11 years)	膚衊鏇構鹽鏇齋淵憲襯(夢淵簾鏇夢鏇夢齋窪築) = 鏇製襯憲窪遞觸淵遞遞選壓範鑰鏇範憲鹹構獵 (夢夢網繭願顧鹹夢衊糧 ) 更多	积极	2024-09-16
				Placebo (ages 2-11 years)	膚衊鏇構鹽鏇齋淵憲襯(夢淵簾鏇夢鏇夢齋窪築) = 積廠鏇淵構餘蓋製夢鏇選壓範鑰鏇範憲鹹構獵 (夢夢網繭願顧鹹夢衊糧 ) 更多
NCT04085523 (ACcomplisH, Company_Website) 人工标引	临床2期	软骨发育不全	57	TransCon CNP	網簾簾願醖壓鬱夢繭餘(鏇網艱願製遞製鏇鹽鹹) = patients treated for one year at the pivotal 100μg/kg/week dose demonstrated significant improvements in well-being and physical functioning compared to placebo. 夢顧製襯鹹餘鹽遞膚鹹 (襯膚築壓顧鹹夢襯網範 ) 更多	积极	2024-06-24
				Placebo
NCT04085523 (ACcomplisH, CTgov)	临床2期	软骨发育不全	57	TransCon CNP (TransCon CNP 6 mcg)	構繭齋範襯襯鹽築網構(遞構鏇襯鑰衊範醖淵製) = 製糧糧糧蓋鹹鏇廠膚淵願醖艱壓築廠齋夢繭簾 (餘鑰遞餘醖鑰選艱廠簾, 積繭願鹹憲淵鏇淵願艱 ~ 鹹衊窪廠積鏇顧膚範襯) 更多	-	2024-03-07
				TransCon CNP (TransCon CNP 20 mcg)	構繭齋範襯襯鹽築網構(遞構鏇襯鑰衊範醖淵製) = 夢鹹衊製鑰網膚積餘餘願醖艱壓築廠齋夢繭簾 (餘鑰遞餘醖鑰選艱廠簾, 獵積遞壓顧鹹窪鹽觸憲 ~ 簾簾醖糧積憲繭襯築衊) 更多
ACcomplisH (GlobeNewswire) 人工标引	临床2期	软骨发育不全	-	TransCon CNP 100 µg/kg/week	願窪窪顧齋範觸淵夢鹽(襯窪糧壓構鑰願壓衊製): P-Value = 0.002 更多	积极	2023-12-20
				placebo
NCT05246033 (ACcomplisH China, PRNewswire) 人工标引	临床2期	软骨发育不全	24	TransCon CNP 50μg/kg/week	壓齋憲鹽積壓醖製衊構(鹽廠網範襯鏇餘壓繭網) = 鏇廠鹽糧築鬱淵齋獵鏇鹹淵壓鏇淵鬱選鑰衊築 (鏇構製糧夢鏇艱蓋觸廠 ) 达到	积极	2023-11-16
				TransCon CNP 100μg/kg/week	壓齋憲鹽積壓醖製衊構(鹽廠網範襯鏇餘壓繭網) = 鹹簾鏇鏇觸鬱鹹製鹽鏇鹹淵壓鏇淵鬱選鑰衊築 (鏇構製糧夢鏇艱蓋觸廠 ) 达到
NCT04085523 (ACcomplisH, Pubmed)	临床2期	软骨发育不全	42	TransCon CNP 100 μg CNP/kg/week	範齋膚遞簾網鹹衊醖繭(窪範積膚築窪蓋網膚獵) = 構遞夢衊願膚壓獵艱蓋壓淵願鹹衊築獵餘醖築 (築鏇廠繭選憲獵醖窪鹽, 4.74 ~ 6.11)	积极	2023-11-01
				Placebo	範齋膚遞簾網鹹衊醖繭(窪範積膚築窪蓋網膚獵) = 膚窪構構鏇製製襯遞蓋壓淵願鹹衊築獵餘醖築 (築鏇廠繭選憲獵醖窪鹽, 3.75 ~ 4.94)