A Phase 3 Randomized Double-Blind Placebo-Controlled Multicenter Study to Assess the Efficacy and Safety of KBP-5074 Mineralocorticoid Receptor Antagonist in Subjects With Uncontrolled Hypertension and Moderate or Severe (Stage 3b/4) CKD

This Phase 3, randomized, Double-blind, placebo-controlled, 2-arm, parallel-group, multicenter study with randomized withdrawal will evaluate the efficacy, safety, and durability of KBP-5074 in adult participants who have stage 3b/4 chronic kidney disease (CKD) (estimated glomerular filtration rate [eGFR] calculated using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula [eGFR {EPI}] ≥15 to ≤44 mL/min/1.73 m^2) and uncontrolled hypertension (systolic blood pressure (SBP) ≥140 and <180 mm Hg and taking 2 or more antihypertensive medications.

开始日期2021-11-05

申办/合作机构

KBP Biosciences USA, Inc.

NCT04634812

/ Completed临床1期

A Phase 1, Open-label, Study of the Absorption, Metabolism, and Excretion of [14C]-KBP-5074 Following a Single Oral Dose in Healthy Male Subjects

This is a Phase 1, open-label, nonrandomized, single-dose mass balance and metabolite identification study in healthy male subjects.

开始日期2020-12-03

申办/合作机构

KBP Biosciences USA, Inc.

[+1]

100 项与阿莫奎尼相关的临床结果

登录后查看更多信息

100 项与阿莫奎尼相关的转化医学

登录后查看更多信息

100 项与阿莫奎尼相关的专利（医药）

登录后查看更多信息

项与阿莫奎尼相关的文献（医药）

2024-11-01·Heart

Diagnosis and management of resistant hypertension

Review

作者: Kreutz, Reinhold ; Cho, Myeong-Chan ; Camafort, Miguel

Resistant hypertension is a condition where blood pressure levels remain elevated above target despite changes in lifestyle and concurrent use of at least three antihypertensive agents, including a long-acting calcium channel blocker (CCB), a blocker of the renin-angiotensin system (ACE inhibitor or angiotensin receptor blocker) and a diuretic. To be diagnosed as resistant hypertension, maintaining adherence to therapy is required along with confirmation of blood pressure levels above target by out-of-office blood pressure measurements and exclusion of secondary causes of hypertension. The key management points of this condition include lifestyle changes such as reduced sodium and alcohol intake, regular physical activity, weight loss and discontinuation of substances that can interfere with blood pressure control. It is also recommended that current treatment be rationalised, including single pill combination treatment where antihypertensive drugs should be provided at the maximum tolerated dose. It is further recommended that current drugs be replaced with a more appropriate and less difficult treatment regimen based on the patient’s age, ethnicity, comorbidities and risk of drug–drug interactions. The fourth line of treatment for patients with resistant hypertension should include mineralocorticoid receptor antagonists such as spironolactone, as demonstrated in the PATHWAY-2 trial and meta-analyses. Alternatives to spironolactone include amiloride, doxazosin, eplerenone, clonidine and beta-blockers, as well as any other antihypertensive drugs not already in use. New approaches under research are selective non-steroidal mineralocorticoid receptor antagonists such as finerenone, esaxerenone and ocedurenone, selective aldosterone synthase inhibitors such as baxdrostat, and dual endothelin antagonist aprocitentan.

2024-06-01·Journal of Diabetes

Renal effects and safety between Asian and non‐Asian chronic kidney disease and type 2 diabetes treated with nonsteroidal mineralocorticoid antagonists

Article

作者: Cui, Yuying ; Feng, Jing ; Li, Pingjiang ; Xu, Xiaoming ; Liao, Lin ; Dong, Jianjun

AbstractBackgroundAsians bear a heavier burden of chronic kidney disease (CKD), a common comorbidity of type 2 diabetes mellitus (T2DM), than non‐Asians. Nonsteroidal mineralocorticoid receptor antagonists (MRAs) have garnered attention for their potential advantages in renal outcomes. Nevertheless, the impact on diverse ethnic groups remains unknown.MethodsThe PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang database, and clinical trial registries were searched through August 2023 with the following keywords: nonsteroidal MRAs (finerenone, apararenone, esaxerenone, AZD9977, KBP‐5074), CKD, T2DM, and randomized controlled trial (RCT). A random effects model was used to calculate overall effect sizes.ResultsSeven RCTs with 14 997 participants were enrolled. Nonsteroidal MRAs reduced urinary albumin to creatinine ratio (UACR) significantly more in Asians than non‐Asians: (weighted mean difference [WMD], −0.59, 95% CI, −0.73 to −0.45, p < .01) vs (WMD, −0.29, 95% CI, −0.32 to −0.27, p < .01), respectively. The average decline of estimated glomerular filtration rate (eGFR) was similar in Asians and non‐Asians (p > .05). Regarding systolic blood pressure (SBP), nonsteroidal MRAs had a better antihypertension performance in Asians (WMD, −5.12, 95% CI, −5.84 to −4.41, p < .01) compared to non‐Asians (WMD, −3.64, 95% CI, −4.38 to −2.89, p < .01). A higher incidence of hyperkalemia and eGFR decrease ≥30% was found in Asians than non‐Asians (p < .01).ConclusionsNonsteroidal MRAs exhibited significant renal benefits by decreasing UACR and lowering SBP in Asian than that of non‐Asian patients with CKD and T2DM, without increase of adverse events except hyperkalemia and eGFR decrease ≥30%.

image

2024-03-01·European Journal of Drug Metabolism and Pharmacokinetics

Pharmacokinetics of the Novel Nonsteroidal Mineralocorticoid Receptor Antagonist Ocedurenone (KBP-5074) in Individuals with Moderate Hepatic Impairment

Article

作者: Yang, Fred ; Benn, Vincent ; Zhang, Jay ; McCabe, James

BACKGROUND AND OBJECTIVESOcedurenone (KBP-5074) is a novel nonsteroidal mineralocorticoid receptor antagonist that has demonstrated safety and efficacy in clinical trials in patients with uncontrolled hypertension and stage 3b/4 chronic kidney disease. The aim of this study was to assess the pharmacokinetics, safety, and tolerability of ocedurenone in individuals with moderate hepatic impairment.METHODSThis study was an open-label, nonrandomized, multi-center study investigating the pharmacokinetics, safety, and tolerability of a single dose of 0.5 mg ocedurenone administered orally in male and female subjects with moderate hepatic impairment (Child-Pugh B, score 7-9) compared with subjects with normal hepatic function. Serial blood samples were obtained from predose through 264 h postdose for analysis of ocedurenone concentrations using a validated liquid chromatography-tandem mass spectrometry method. Free ocedurenone concentrations in plasma were determined ex vivo using equilibrium dialysis.RESULTSFollowing a single oral dose of 0.5 mg ocedurenone administered to subjects with moderate hepatic impairment and subjects with normal hepatic function, ocedurenone was steadily absorbed with median time to peak drug concentration (T_max) values of 4 and 3 h, respectively. After reaching maximum plasma concentration (C_max), the disposition of ocedurenone appeared to be biphasic. The geometric mean t_1/2 values for the moderate hepatic impairment group and normal hepatic function group were 75.6 and 65.7 h, respectively. Ocedurenone systemic exposure, as assessed by area under the plasma concentration-time curve (AUC) was 23.5-26.6% lower in subjects with moderate hepatic impairment versus subjects with normal hepatic function, whereas C_max was 41.2% lower. Ocedurenone was determined to be > 99.7% bound to total protein in plasma. Hepatic impairment appeared not to change plasma protein binding or the unbound free fraction. Ocedurenone was safe and well-tolerated in all participants.CONCLUSIONSConsidering the long half-life of ocedurenone and previously completed clinical studies using 0.25 mg and 0.5 mg doses demonstrating efficacy and safety, the observed decreases in AUC and C_max do not warrant a dose adjustment in patients with moderate hepatic impairment. A single 0.5 mg dose of ocedurenone was safe and well-tolerated when administered to subjects with moderate hepatic impairment and subjects with normal hepatic function. CLINICAL TRIAL IDENTIFIER ( WWW.CLINICALTRIALSGOV ): NCT04534699.

项与阿莫奎尼相关的新闻（医药）

2025-01-06

·医学新视点

降压药已经发展到什么程度了？4大新型降压药进展盘点

高血压是心血管疾病的风险因素，也是全球人口过早死亡的主要原因。尽管高血压人群庞大，但据《柳叶刀》2021年的数据统计，在接受治疗的高血压人群中，大约只有1/5的人血压得到了足够的控制。药物的依从性差是影响高血压控制率的原因之一。尽管目前能够有效降压的药物超过10种，但现有的治疗手段仍不能满足所有的治疗需求。因此，研究者们仍在探索新的治疗方法，寻求更有效且持久的降压策略。近期，Circulation杂志发表了一篇针对降压药物的综述，文章总结了目前降压新药的研究进展，多款药物的研究数据已经显示出了长效或肾脏、心血管疾病获益。 1 醛固酮靶向治疗醛固酮失调是许多高血压患者的发病原因，醛固酮受体拮抗剂（MRA）分为甾体MRA和非甾体MRA，已经获得全球指南推荐用于治疗心衰、高血压患者。非甾体MRA的降压能力各不相同。例如，esaxerenone在日本获批用于高血压治疗，但另一款非甾体MRA药物ocedurenone在Clarion-CKD试验中未能显著降低血压。与此同时，抑制醛固酮合成酶的药物（ASI）正在开发中，以降低血压而不产生MRA的副作用。其中，比较热门的是lorundrostat和baxdrostat。 Lorundrostat的初始血压数据来自Target-HTN试验，关键试验的结果预计将于2025年公布。 Baxdrostat的两项试验则提供了相互矛盾的结果。BrigHTN 试验表明，服用至少3种降血压药物的参与者血压显著降低[2 mg剂量组与安慰剂组之间收缩压的最小二乘法差值为-11.0 mmHg （95% CI，-16.4~-5.5；P<0.001）]。而 HALO 试验显示，与安慰剂相比，血压降低没有统计学意义。 2 血管紧张素原靶向治疗血管紧张素原作为肾素-血管紧张素-醛固酮系统（RAAS）的最上游成分，是降低血压的一个有效靶点。血管紧张素原主要在肝脏产生，使其成为 N-乙酰半乳糖胺（GalNAc）偶联RNA基治疗的理想目标。标准RAS药物如血管紧张素转换酶抑制剂（ACEI）和血管紧张素 II 受体阻滞剂（ARB），长期使用会导致肾素代偿性升高，继而造成RAS逃逸。而小干扰RNA（siRNA）疗法可以防止RAS逃逸，使肾素代偿性上升，从而获得更有效的 RAS 抑制和长期血压控制的优势。 ▲GalNAc-AGT-siRNA（A）；RAS逃逸与siRNA药物机制（B） Zilebesiran是一种靶向血管紧张素原的siRNA。研究显示，在未服用任何降压药物的高血压患者中，单剂量zilebesiran显示出持续6个月的血压降低效果。与安慰剂相比，不同剂量的zilebsiran的24小时平均动态收缩压降低14~17 mmHg。正在进行的KARDIA-3研究正在评估zilebesiran在服用2~4种药物患者中降低血压的能力。 ▲Zilebesiran（150 mg，每6个月一次）和安慰剂组24小时平均动态收缩压变化 3 GLP-1和GIP受体激动剂 25%~75%的高血压可归因于肥胖。胰高血糖素样肽受体1（GLP-1）激动剂和联合GLP-1/GIP受体激动剂在治疗肥胖、动脉粥样硬化性心血管疾病和心力衰竭等疾病方面有效，因此，这些药物可能对治疗顽固性高血压甚至初始高血压治疗有益，并且有证据表明GLP-1受体激动剂可以显著减少临床上重要的肾脏事件。 SURMOUNT-1的24小时动态血压亚组研究显示，在基线血压为125 mmHg的人群中，与每周10 mg剂量的安慰剂相比，每周一次的替尔泊肽使收缩压降低了>10 mmHg。 ▲白天和夜间血压的结果均显示，与安慰剂相比，每种剂量的替尔泊肽治疗都显著降低24小时收缩压 4 NPR1受体激动剂利钠肽（NPs）通过利钠肽受体1（NPR1）调节血管张力。激活NPR1可以降低血压，并影响钠排泄和利尿。 XXB750是一种NPR1激动剂，通过皮下给药，其2期剂量寻找研究已完成，结果待定。 REGN5381是一种激活NPR1的单克隆抗体，目前在早期临床试验中产生了预期的血流动力学效应，表现出静脉压的降低，但利尿和利钠没有明显体现。近期获批的降压新疗法一览 2024年3月，美国FDA批准了双重内皮素受体拮抗剂aprocitentan用于治疗高血压。尽管其3期试验中的收缩压降低幅度（4~6 mmHg）并不令人满意，但其不升高血清钾和对肾功能中性影响，可能使其成为慢性肾脏病患者的谨慎选择。 2023年11月，美国FDA批准了射频和超声波肾脏去神经治疗，旨在证明一次性基于导管的干预可以有效降低血压，提供了除改变生活方式、药物外的另一种高血压治疗选择。总结新的治疗选择正在不断涌现，未来的高血压研究可能将进一步找到上述新疗法对应降压效果更显著的患者表型。例如，由醛固酮失调引起的高血压患者可能最适合使用ASI治疗，而与肥胖相关的高血压患者可能最适合使用GLP1受体激动剂作为前线治疗。相信随着新疗法的不断涌现和研究的深入，我们有望看到更多有效的治疗选择，以应对高血压这一全球性健康挑战。相关阅读氨氯地平、吲达帕胺、培哚普利，两两组合，哪种降压效果更佳？| AHA 2024速递血压120 mmHg更适合中国糖尿病患者！瑞金医院领衔研究登上NEJM，为“最优”降压值提供新证据安贞医院周玉杰领衔：强效降压25.2 mmHg！微创手术有望为中国高血压患者带来新选择 1片顶3片！《柳叶刀》：单片复方制剂额外降压6.3 mmHg，高达96%患者可坚持用药 4倍血压达标率！阜外医院领衔研究：一次微创手术，长期有效降压欢迎投稿：学术成果、前沿进展、临床干货等主题均可，点此了解投稿详情。参考资料（可上下滑动查看） [1]NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants. Lancet. 2021 Sep 11;398(10304):957-980. [2]Laffin LJ. Future of Antihypertensive Therapies. Circulation. 2024 Dec 17;150(25):1987-1989. doi: 10.1161/CIRCULATIONAHA.124.072417. Epub 2024 Dec 16. [3]Verma S, Pandey A, Pandey AK, et al. Aldosterone and aldosterone synthase inhibitors in cardiorenal disease. Am J Physiol Heart Circ Physiol. 2024;326:H670–H688. [4]Ranasinghe P, Addison ML, Webb DJ. Small Interfering RNA Therapeutics in Hypertension: A Viewpoint on Vasopressor and Vasopressor-Sparing Strategies for Counteracting Blood Pressure Lowering by Angiotensinogen-Targeting Small Interfering RNA. J Am Heart Assoc. 2022 Oct 18;11(20):e027694. [5]Bakris GL, Saxena M, Gupta A, et al; KARDIA-1 Study Group. RNA interference with zilebesiran for mild to moderate hypertension: the KARDIA-1 randomized clinical trial. JAMA. 2024;331:740–749. [6]Badve SV, Bilal A, Lee MMY, et al. Effects of GLP-1 receptor agonists on kidney and cardiovascular disease outcomes: a meta-analysis of randomised controlled trials. Lancet Diabetes Endocrinol. 2024 Nov 25:S2213-8587(24)00271-7. [7]de Lemos JA, Linetzky B, le Roux CW, et al. Tirzepatide Reduces 24-Hour Ambulatory Blood Pressure in Adults With Body Mass Index ≥27 kg/m2: SURMOUNT-1 Ambulatory Blood Pressure Monitoring Substudy. Hypertension. 2024 Apr;81(4):e41-e43. [8]Dunn ME, Kithcart A, Kim JH, et al. Agonist antibody to guanylate cyclase receptor NPR1 regulates vascular tone. Nature. 2024 Sep;633(8030):654-661. 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。分享，点赞，在看，传递医学新知

siRNA临床结果信使RNA

2024-12-18

·FierceBiotech

Novo Nordisk taps Photys for $186M cardiometabolic collab

Photys Therapeutics is on deck to tackle preclinical efforts, while Novo Nordisk is slated to take the potential assets through IND-enabling studies and clinical development. \n With Novo Nordisk’s name already synonymous with treatments for diabetes and obesity, the Danish drugmaker has been making a concerted push to bolster its pipeline beyond GLP-1 stalwarts Ozempic and Wegovy, branching out into other cardiometabolic conditions like metabolic dysfunction-associated steatohepatitis (MASH) and chronic kidney disease (CKD).Now, as part of that development odyssey, the company is tapping into an emerging protein technology from Photys Therapeutics.Under a new research collaboration unveiled Wednesday, Novo will pay Photys up to $186 million in upfront, development and commercial milestone payments to help develop proximity-based therapeutics for an unnamed cardiometabolic disease target.The deal—which will also see Photys receive R&D funding and potential tiered royalties on commercial sales—hinges on the biotech’s Phosphorylation Inducing Chimeric Small molecules (PHICS) technology. The company has designed its proprietary platform to induce proximity between a kinase and a protein of interest in order to phosphorylate that target and change its biologic function, Photys explained in a release.Novo and Photys plan to work together on multiple PHICS molecules for their chosen cardiometabolic target. Photys is on deck to tackle preclinical efforts, while Novo is slated to take the potential assets through investigational new drug-enabling studies and clinical development, the partners said.“This collaboration represents a strong alignment between the desire to control a critical protein and a technology capable of doing so in a tissue-specific manner,” Alexandra Joseph, Ph.D., Photys’ chief scientific officer, said in a statement.Meanwhile, Novo’s corporate vice president and therapeutic area head of diabetes, obesity and MASH, Bei Zhang, Ph.D., said the deal could allow her company to reach important protein targets “with a high degree of efficacy and selectivity.” Photys, which is based right next to Boston in Waltham, Massachusetts, uncloaked in 2022 with $75 million in funds from Merck & Co.’s MRL Ventures Fund, Eli Lilly, Arkin Bio and Mass General Brigham Ventures, among others.The biotech has stayed relatively quiet over the last two years, with the October appointment of Joseph the most recent update on the company’s website.Novo Nordisk, for its part, has been working hard to enrich its cardiometabolic pipeline in areas beyond diabetes and obesity, where the company currently dominates the commercial market with its respective GLP-1 medicines Ozempic and Wegovy.So far, the company’s success has been somewhat mixed.Back in May, Novo unveiled full results from its FLOW trial showing that a once-weekly 1-mg dose of semaglutide—the molecule behind Ozempic and Wegovy—helped combat major kidney outcomes like kidney failure, loss of kidney function and death from kidney or cardiovascular causes in people with Type 2 diabetes and CKD.At the time, Novo’s executive medical director, Michael Radin, M.D., told Fierce Pharma the results could “really move the needle” and set a new standard for “holistic” care for many patients living with both diabetes and kidney disease.Additionally, 2.4-mg semaglutide recently excelled in a phase 3 study of MASH patients, prompting Novo to ready filings for submission to regulators in Europe and the U.S. in the first half of 2025. Still, Novo has been less fortunate with external cardiometabolic efforts, as evidenced by the drugmaker’s decision in early November to scrap a late-stage kidney drug acquired through a $1.3 billion deal with KBP Biosciences.Novo had hoped the CKD prospect, dubbed ocedurenone, could eventually rival Bayer’s Kerendia. But those hopes were dashed when the nonsteroidal mineralocorticoid receptor antagonist missed its primary endpoint at the time of a prespecified interim analysis. With ocedurenone gone, the only CKD program still listed in Novo’s pipeline is semaglutide.

临床3期高管变更

2024-12-05

·深蓝观

BD浪潮，卷走中国创新药青苗？

韦晓宁 | 撰文高翼 | 编辑 2024年接近尾声，今年的BD浪潮再创新高，业内却是几家欢喜几家愁。业内统计，去年国内发生近70笔license out交易，而今年光是第三季度，license out的案例就超过了30笔。国内由恒瑞医药开启的“newco”模式再次点燃从业者的热情。从前只是MNC来扫货，如今美元基金也加入战场，中国资产炙手可热，连带在美的华人从业者也变得受欢迎。 BD是主流，是pharma验证自身资产质量的有效路径，是biotech的自救手段甚至就是生存方式本身。IPO难、融资环境差、支付力量有限，在国内创新药界，BD的必要性已是毋庸置疑。但与此同时，一些听上去似乎有些杞人忧天的声音开始出现：BD潮如此汹涌，当中不乏有best-in-class潜力、进度较快的管线。未来，中国本土会不会就没有新药可上了？如果大家的创新都只是奔着“卖给大厂”，而非在国内落地，来参加医保谈判的都变成进口药，国产无新药可谈，因而价格变贵？一个可以参考的答案是，一部分将全球所有权益都授予出去、甚至公司一起被并购的管线，的确有可能就此走海外路线，和国产药形成不同的研发和市场策略、价格体系，这也是由发展环境和市场容量自然决定的；而保留了中华区权益的管线，其国内的商业化前景，也有可能在BD后受到一些影响。 -01-BD后，国产新药何去何从？按照授权方处理的方式，当下BD可以分为三种，分别是保留中华区权益和不保留中华区权益，以及公司直接被并购。第一种是将海外权益授予出去，大中华区权益保留。理论上，这种授权方式，国内的biotech依旧有将相关管线做成国产药的可能，只是国内外研发、注册进度有差别。以康方生物为例，早在2015年，康方就一款CTLA-4单抗（AK-107）的海外权益授予默沙东，但至今仍未在美上市，而康方自研的PD-1/CTLA-4双抗卡度尼利，在2022年6月已在国内上市。在针对CTLA-4靶点的双抗已经出炉的情况下，MNC可能已经放弃推进单抗管线的研发。亦有因MNC战略调整而退掉管线的情况发生，百济神州、科伦博泰和天境生物都曾有知名的被“退货”事件发生，在本就保有中华区权益的基础上，“重获全球权益”也成为常态。 MNC管线繁多，精力分散，买下早期的管线“试试水”，或只是抱着提前“消灭”未来竞争对手的心态，都可能会造成交易方对后续重视程度不够、推进不力的情况。 BD授权出去的管线，海外市场优先安排的目前出圈的只有传奇生物与强生合作的CAR-T西达基奥仑赛。西达基奥仑赛于2022年2月在美国上市，售价46.5万美元/针；2024年8月在中国上市，定价将和国内其他的CAR-T产品一样在100万元人民币左右，但据称目前在国内仍未开始销售。业内人士推测，CAR-T产品在欧美市场需求大、产能有限，而国内的价格也无法突破同类已上市产品的级别，因此西达基奥仑赛在国内“不急着上市和销售”。 CAR-T制药成本高，价格在国内外都居高不下。而其他药物，中美价差更甚，动辄可达二十倍、三十倍。因此，理论上这种可能性是存在的：中国的biotech将产品授权出去、美国上市后，轻松拿着销售分成，因而并不着急将产品在国内上市，不过“按利润最大化原则，国内不可能故意不上，只是没那么上心所以晚一点”。比起MNC，biotech进行大型临床试验的能力有限，注册方面太过先进的靶点有时还要先经FDA的“验证”，因此产品在国内若是晚些上市也无法苛责。毕竟，若是不BD，在IPO和融资环境不见向好的情况下，别说新药晚些上市，就是公司能不能活下去可能都是个问题。更多人担心的是，因为全球定价体系的存在，以及能在美国市场上市的背书，即便药品分为国外和国产两个版本，国产药的定价是否仍然会受国外影响而变贵？不过，目前已在中美两个市场上市的泽布替尼、特瑞普利单抗、呋喹替尼、西达基奥仑赛，都说明了“BD后国产药变贵”的担忧很可能是多余的。中美产品的价差依然巨大，国内定价体系是比较独立的，很难脱离国内的支付能力和同类产品定价的限制，“尤其是想进医保就得按医保的体系来。境内即使不进医保的产品，定价也不会随便来，都是要考虑国内购买力的。” 有熟悉商业化的人士称，在BD交易中，对于中国的定价，“国内权利拥有者肯定会约定具有最终决定权”，不会轻易完全被合作方左右。 -02-来自中国的“进口”药虽然保留中华区权益是主流的做法，也是有biopharma之志者必然会选择的方式；但也有想得更清楚的biotech，将管线完全授权了出去，公司的使命很可能也到此为止。亨利医药，2023年10月将治疗慢性肾脏病患者高血压的产品Ocedurenone授权给诺和诺德，交易总额13亿美元。但很快八个月后诺和诺德就宣布Ocedurenone三期临床失败，项目终止。但对亨利医药来说，一部分预付款必定已落袋为安，以Ocedurenone的所有权益换来13亿美元的合作金额，没有保留中国区权益，某种程度而言也是提前规避了风险。同润生物，今年8月宣布将一个已进入临床的CD3×CD19 TCE双抗全球权益授权给默沙东，并未提及保留中华区权益、并未提及后续分成。这意味着默沙东可能“买断”了这个产品的权益，而这是国内唯一一个进入了临床阶段并出现临床数据的CD3×CD19 TCE双抗。虽然能不能最终成药、会不会在国内上市还有诸多不确定性，但未来若是在国内上市，该药很可能会是进口药的身份，而且上市时间可能早于国内同类药物。中国管线的“半成品”出口，而后成品以进口药的身份归来，价格贵些，是一种可能的结局。另一种结局是，国外的管线买方因为种种考虑而放弃中国市场，或者是很晚才推进将药物在中国上市。从这个角度而言，创新的种子还未长成果实就被别人买走，确实可能会为让国内享受创新成果增加许多不确定性。但在商言商，还是那个结论——若是不BD，别说新药能不能在国内上市、进口药的身份会不会更贵，就是公司能不能活下去可能都是个问题。还有一批公司直接被MNC并购，产品若上市，进口药身份几乎可以确定。分析这批公司的核心管线会发现，MNC的确会挑选有进度最快、有best-in-class潜质管线的公司收购。亘喜生物，去年底“打响中国biotech卖身第一枪”，其CD19/BCMA双靶点CAR-T治疗难治性系统性红斑狼疮的适应证已在美国拿到IND，在同类产品中进度走在全球前列。有人认为，在自免领域大热的背景下，这是阿斯利康收购亘喜生物的直接原因之一。葆元医药，被Nuvation Bio以全股票交易方式收购，公司的ROS1抑制剂、IDH1抑制剂都已进入临床二期、有同类最佳潜质，前者已在中美两国被授予突破性疗法资格、在中国被授予新药申请优先审评资格。普方生物，被Genmab以18亿美元全现金方式收购，它有市场上为数不多的FRα靶点ADC，目前已进入临床三期，进度处在全球前列；信瑞诺医药，也是因为有两个处在临床三期的IgA肾病产品，才被诺华看中。普米斯的PD-L1/VEGF在临床三期的阶段，公司被BioNTech收购、买下原属普米斯的中华区权益。在行业人士看来，因为融资和产业培育体系成熟度的问题，国内创新药管线在“半成品阶段”就出口是必然的，也是无解的。未来国内外用药可能会形成两种体系，“普通人用医保，医保会满足大家最基础的治疗要求，解决有没有的问题；有能力的人是自费，用进口药或者去国外治病，解决好不好的问题。” -03-BD的风是一种市场选择新药研发是一场高投入、高回报的冒险游戏，而一个大家越来越不得不面对的事实是，这个循环生态系统的闭环在国内需要经历一些调整：现阶段医保是最大的单一支付方，要承担保证老百姓基本医疗的同时，已坚持纳入了部分创新药。但医保身上的担子太重，决定了创新药像在美国那样的“高回报”无法成立；在生物制药的寒冬中，基金对上市IPO难、药品销售也不及预期的Biotech驻足观望，宣告了“高投入”此时亦难以达成。往海的那边去，做MNC的研发基地，融入高定价市场的逻辑成为全球制药行业的共识。Biotech必须以BD为目的开发管线，而pharma的愿景则变成了：在global赚取高额的市场回报，而后反哺平价的中国市场。业内人士认为，国内pharma离实现这样的愿景也还有很长一段距离。拿两家具有代表性的药企讨论，百济神州具有国际化的基因，从研发、注册到销售都已在全球市场验证过。但其规模在国际上仅是一家中型biopharma，后续自研的管线还没有明确有best-in-class潜质的，“大量license in，而后快速推进研发和销售”的飞轮还未转动起来；而恒瑞医药，目前仍是“国内biotech BD时最大的对手”，与biotech是竞争而非合作关系。大量价优质高的管线、较好的品牌效应，使其成为MNC挑选管线的大超市。但其自身，并未有任何一个产品在国外走通过高投入与高回报的路线。新药研发的自我循环尚未实现，中国并未出现哪一家企业可以充当MNC的角色，去为biotech可以license out的管线甚至并购买单。因此即便有实力强劲的专业基金出现，助力biotech本土融资甚至是打造newco，biotech的买单方依旧在海岸对面。许多人还记得七八年前创新药行业的百废待兴之势。但不是有众多人口和理论上广阔的市场、一批有才华有热情的科学家、开放了一时的融资窗口，就可以成就一个完整的新药产业。数年下来的曲折发展揭示，政策、支付、资本、产业积累，每一个环节都需要适当和稳固的条件，才能达成这新药研发的闭环逻辑。新模式的可能固然令人向往，甚至把人冲昏头脑。而当泡沫萎缩、新模式还无法被验证时，市场的风向会将这些涌现的资源推到合理的位置，一切就顺其自然，难以去指摘。 ...... 欢迎添加作者交流：韦晓宁：MoriW1995 内容合作：17610790527

并购细胞疗法免疫疗法IPO引进/卖出

100 项与阿莫奎尼相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
肾病	临床3期	美国	山东亨利医药科技有限责任公司	-
慢性肾病	临床1期	马来西亚	KBP Biosciences USA, Inc.	2021-11-05
慢性肾病	临床1期	韩国	KBP Biosciences USA, Inc.	2021-11-05
慢性肾病	临床1期	波斯尼亚和黑塞哥维那	KBP Biosciences USA, Inc.	2021-11-05
慢性肾病	临床1期	德国	KBP Biosciences USA, Inc.	2021-11-05
慢性肾病	临床1期	格鲁吉亚	KBP Biosciences USA, Inc.	2021-11-05
慢性肾病	临床前	格鲁吉亚	KBP Biosciences USA, Inc.	2021-11-05
慢性肾病	临床前	韩国	KBP Biosciences USA, Inc.	2021-11-05
慢性肾病	临床前	马来西亚	KBP Biosciences USA, Inc.	2021-11-05
慢性肾病	药物发现	波斯尼亚和黑塞哥维那	KBP Biosciences USA, Inc.	2021-11-05

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04968184 (CLARION-CKD, NEWS) 人工标引	临床3期	高血压 \| 慢性肾病	600	ocedurenone	(觸構獵醖糧選夢廠顧選) = failed to meet its primary endpoint 網遞鑰積醖鹽構衊糧窪 (糧願觸築構壓獵鏇壓選 ) 未达到	不佳	2024-06-27
ASN2022	N/A	肝功能不全	-	KBP-5074 0.5 mg	(顧窪窪壓鹹艱顧艱廠繭) = 糧膚願膚醖壓觸膚壓襯觸範淵鬱衊淵鹹艱簾遞 (鹹構齋窪艱醖繭願顧壓 ) 更多	积极	2022-11-04
				KBP-5074 (Healthy Control Group)	(顧窪窪壓鹹艱顧艱廠繭) = 衊窪鏇範夢餘壓觸築願觸範淵鬱衊淵鹹艱簾遞 (鹹構齋窪艱醖繭願顧壓 ) 更多
NCT03574363 (BLOCK-CKD, Pubmed \| Hypertension)	临床2期	慢性肾病	162	Placebo	(襯壓窪遞願壓餘網糧遞) = 餘構醖鬱鹹獵獵構鑰鏇餘壓鏇艱簾蓋鏇壓膚廠 (憲積鏇膚壓鏇選觸範窪 )	积极	2021-07-01
				KBP-5074 0.25 mg	(襯壓窪遞願壓餘網糧遞) = 簾衊鹹衊窪廠醖網淵顧餘壓鏇艱簾蓋鏇壓膚廠 (憲積鏇膚壓鏇選觸範窪 )
NCT02837237 (CTgov)	临床1期	慢性肾病	11	KBP-5074	繭醖遞鏇積製鑰網醖築(積餘製膚範積築構蓋齋) = 廠淵齋齋壓範糧顧願夢膚簾鹹鬱選繭鏇鏇鏇觸 (鏇願鬱襯鑰鬱鏇鬱選膚, 膚鹽壓襯壓遞觸鑰餘簾 ~ 廠膚觸窪遞鹹顧製鹽廠) 更多	-	2019-10-15
ASN2017	临床1期	慢性肾病	11	KBP-5074 0.5 mg	(顧廠簾齋觸積窪選顧鏇) = 夢齋醖遞願壓鹽鑰壓壓餘顧蓋鹹製糧衊鑰構鹹 (製蓋築範遞鏇醖窪鹹鏇 ) 更多	积极	2017-10-31
				KBP-5074 (Hemodialysis)	(顧廠簾齋觸積窪選顧鏇) = 蓋鑰繭鏇餘鹹積廠窪淵餘顧蓋鹹製糧衊鑰構鹹 (製蓋築範遞鏇醖窪鹹鏇 ) 更多
ASN2016	N/A	慢性肾病	14	KBP-5074 0.5 mg	(憲鏇齋壓齋構憲構願鏇) = 2 subjects in the 2.5 mg group developed hyperkalemia (serum potassium >5.5 mmol/L); 1 subject in the 0.5 mg group with baseline serum potassium 5.0 mmol/L also developed hyperkalemia on study. These three subjects continued in the study. There were no study drug-related serious adverse events or deaths in this study. 壓襯衊衊醖鹽網醖顧鑰 (齋衊鏇範範餘鑰構構蓋 )	积极	2016-11-15
				KBP-5074 2.5 mg