Concizumab-mtci

强效降脂近90%！赛诺菲近4亿美元助力潜在“first-in-class”疗法开发Arrowhead Pharmaceuticals今日宣布，其控股子公司维亚臻（Visirna Therapeutics）与赛诺菲（Sanofi）签署协议。根据协议条款，赛诺菲将获得在大中华区开发和商业化在研疗法plozasiran（VSA001）的独家权利。Plozasiran是一款潜在“first-in-class”的siRNA疗法，旨在抑制载脂蛋白C-III（APOC3）的产生，用于治疗家族性乳糜微粒血症综合征（FCS）及重度高甘油三酯血症（SHTG）。根据协议，赛诺菲将向维亚臻支付1.3亿美元的预付款，并在未来根据监管里程碑支付最高2.65亿美元。维亚臻此前已完成在中国FCS患者中的plozasiran临床3期试验，试验成功达到主要疗效终点及所有关键次要终点。之前公布的试验结果显示，plozasiran在第10个月使患者的中位甘油三酯水平降低高达89%，中位APOC3水平降低高达93%，与安慰剂组相比具有统计学差异。维亚臻已于2025年1月向中国国家药品监督管理局（NMPA）递交新药上市申请，并获得正式受理。此次合作将进一步推动plozasiran在大中华区的临床应用进程，有望为高甘油三酯血症患者带来新的治疗选择。诺和诺德单抗再获FDA批准诺和诺德（Novo Nordisk）日前宣布，美国FDA已批准Alhemo（concizumab）注射液用于预防或减少血友病A（HA）与血友病B（HB）成人及儿科患者的出血发作频率，这些患者年龄12岁及以上且体内无抑制物。新闻稿指出，当前多数无抑制物血友病患者的治疗多依赖静脉输注，而Alhemo作为一种每日一次的皮下注射药物，为该人群提供了更便捷的预防治疗选择。Alhemo是一种组织因子途径抑制剂（TFPI）拮抗剂，此次批准是在2024年12月获批适应症（用于体内含有抑制物的HA/HB患者）基础上的扩展。此次批准主要基于3期临床试验explorer8的结果，研究证实Alhemo在12岁及以上无抑制物的HA/HB患者中具有良好的安全性与疗效。试验显示，在无抑制物的HB患者中，年化出血率（ABR）降低79%；在HA患者中，ABR降低幅度更高，达到86%。近半晚期RAS突变癌症患者获得缓解，小分子抑制剂积极结果公布Cardiff Oncology近日公布其正在进行的CRDF-004试验的积极结果。该研究是一项随机的2期临床试验，评估候选小分子onvansertib联合标准治疗（SoC）在一线RAS突变型转移性结直肠癌（mCRC）患者中的疗效与安全性。数据显示，在意向治疗人群（N=110）中，接受30 mg剂量onvansertib治疗的患者组确认客观缓解率（ORR）达49%，显著优于对照组的30%。此外，早期无进展生存期（PFS）数据亦显示出30 mg onvansertib组较对照组具有更好的临床获益。研究进一步表明，onvansertib在多个疗效指标上展现出剂量依赖性的积极应答，包括早期肿瘤缩小率及缓解深度，且整体耐受性良好。这一结果支持onvansertib作为一线治疗RAS突变型mCRC的潜力。Onvansertib是一种潜在“first-in-class”的第三代口服PLK1抑制剂。PLK1是Polo样激酶家族成员之一，在乳腺癌、前列腺癌、卵巢癌、肺癌和直肠癌等多种实体瘤和血液癌症中高度表达。PLK1被认为是维持细胞正常分裂的基石之一。研究显示，RAS的激活会引发PLK1的激活，导致细胞分裂和肿瘤增殖，因此，通过抑制PLK1的活性，onvansertib有望抑制肿瘤生长。参考资料：[1] Cardiff Oncology Announces Positive Data from Ongoing Randomized Phase 2 First-line RAS-mutated mCRC Clinical Trial (CRDF-004). Retrieved August 1, 2025 from https://investors.cardiffoncology.com/news-releases/news-release-details/cardiff-oncology-announces-positive-data-ongoing-randomized[2] FDA approves Alhemo® as once-daily prophylactic treatment to prevent or reduce the frequency of bleeding episodes for adults and children 12 years of age and older with hemophilia A or B (HA/HB) without inhibitors. Retrieved August 1, 2025 from https://www.prnewswire.com/news-releases/fda-approves-alhemo-as-once-daily-prophylactic-treatment-to-prevent-or-reduce-the-frequency-of-bleeding-episodes-for-adults-and-children-12-years-of-age-and-older-with-hemophilia-a-or-b-hahb-without-inhibitors-302519177.html[3] Arrowhead Subsidiary Visirna Sells Rights to Hypertriglyceridemia Candidate Plozasiran in Greater China to Sanofi. Retrieved August 1, 2025 from https://www.businesswire.com/news/home/20250801023769/en/Arrowhead-Subsidiary-Visirna-Sells-Rights-to-Hypertriglyceridemia-Candidate-Plozasiran-in-Greater-China-to-Sanofi免责声明：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：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

The FDA cleared additional indications for Novartis’s cholesterol-lowering drug Leqvio (inclisiran) and Novo Nordisk's haemophilia prophylactic Alhemo (concizumab-mtci), broadening their use to wider patient populations.Leqvio gets go-ahead as montherapyNovartis's twice-yearly injectable siRNA drug Leqvio was approved by the FDA as monotherapy alongside diet and exercise to lower low-denisty lipoprotein cholesterol (LDL-C) in adults with hypercholesterolaemia, thereby eliminating the previous requirement for concurrent statin therapy.“With this new indication enabling Leqvio's use as monotherapy…we now have the potential to help even more patients achieve their LDL-C lowering goals earlier in their treatment journey," said Victor Bultó, president of Novartis US.The US regulator said Leqvio’s broader indication was approved based on strong LDL-C-lowering data from PCSK9-targeting therapies. Additional label updates include replacing "primary hyperlipidaemia" terminology with the more specific "hypercholesterolaemia" designation throughout the prescribing information.Novartis noted the decision also aligns with the 2025 American College of Cardiology/American Heart Association Clinical Practice Guidelines, recommending more aggressive treatment approaches for patients with acute coronary syndrome.Leqvio was discovered by Alnylam and co-developed with The Medicines Company, which Novartis acquired in 2020 for $9.7 billion. First approved in the EU for hypercholesterolaemia or mixed dyslipidaemia in 2020, the siRNA’s US approval faced initial delays owing to manufacturing issues, but was subsequently cleared by the FDA in 2021 for patients on maximally tolerated statin therapy.The Swiss drugmaker expects Leqvio not only to surpass $1 billion in sales this year, but potentially outperform consensus forecasts long term. For more, read – Spotlight On: Novartis' fastest growing drugs.Alhemo cleared for patients without inhibitorsThe FDA also okayed an expanded indication for Novo Nordisk's Alhemo (concizumab-mtci), extending its prophylactic use to adult and paediatric patients aged 12 and older with haemophilia A or B without inhibitors. The latest approval builds upon the tissue factor pathway (TFPI) inhibitor antagonist’s approval last year for patients with inhibitors after being rejected by the agency on the first attempt.Anna Windle, senior VP of clinical development, medical & regulatory affairs at Novo Nordisk, said the latest approval “marks a meaningful step forward for people with haemophilia A or B without inhibitors who are looking for a new prophylaxis treatment option."The label expansion was supported by the Phase III explorer8 study, wherein Alhemo achieved an 86% reduction in annualised bleeding rate for patients with haemophilia A and 79% reduction for those with haemophilia B versus no prophylaxis.Following a positive recommendation by the EU drug advisory body last week, the anti-TFPI monoclonal antibody is also on the verge of approval in Europe for the same indication.With the additional indication, Alhemo emerges as a potential rival to Pfizer’s once-weekly Hympavzi (marstacimab-hncq), approved last year for patients without inhibitors. Pfizer also seeks Hympavzi’s expansion to patients with inhibitors following a successful Phase III study.