Baxdrostat

AstraZeneca is evaluating baxdrostat in a range of trials.\n AstraZeneca’s hypertension pill baxdrostat lowered blood pressure by almost 10 mmHg at the higher dose in a phase 3 trial, the Big Pharma has revealed as it gears up to seek approval.The drugmaker evaluated the aldosterone synthase inhibitor in a late-stage study of 796 patients with uncontrolled hypertension who received either 1-mg or 2-mg daily doses of baxdrostat, or placebo, for 12 weeks. AstraZeneca already announced back in July that the study had hit its key goal of demonstrating a statistically significant and clinically meaningful reduction in patients’ mean seated systolic blood pressure (SBP).At the European Society of Cardiology Congress in Spain on Saturday, AstraZeneca served up the data behind that late-stage win. Specifically, the 1-mg and 2-mg doses were tied to placebo-adjusted SBP reductions of 8.7 mmHg and 9.8 mmHg, respectively, at 12 weeks.The results were consistent across both uncontrolled and treatment-resistant subgroups, AstraZeneca noted.When it came to secondary endpoints, both doses led to greater reductions in diastolic blood pressure than placebo and “nearly tripled” the odds of patients reaching their target SBP of less than 130 mmHg, the company added in the Aug. 30 release.Baxdrostat—which CinCor in-licensed from Roche before the biotech was then acquired by AstraZeneca in January 2023—is designed to lower levels of aldosterone, a hormone that regulates blood pressure, without affecting cortisol synthesis. Selectivity for CYP11B2, the gene that encodes aldosterone synthase, over CYP11B1, a gene involved in cortisol synthesis, is needed if drugs that treat cardiovascular diseases by lowering aldosterone levels are to succeed. The $1.3 billion upfront payment that AstraZeneca handed over for CinCor looked like something of a gamble at the time, coming just weeks after baxdrostat missed the key endpoint of a phase 2 trial. But AstraZeneca—which, it later transpired, had been keeping an eye on baxdrostat for a while—used the failed trial to secure significantly improved terms for the acquisition.In the Aug. 30 release, Sharon Barr, executive vice president of biopharmaceuticals R&D at AstraZeneca, said the company is now planning to “advance[e] our regulatory filings for baxdrostat with health authorities in the months ahead.”“The BaxHTN phase 3 results demonstrate baxdrostat’s potential in tackling one of the toughest challenges in cardiovascular care, which is hypertension that is hard to control despite multiple therapies,” Barr added.AstraZeneca is also evaluating baxdrostat in a range of other trials, including a phase 3 study looking at the drug’s 24-hour ambulatory effects, which is expected to read out later this year.The company is “rapidly progressing a robust clinical development program across indications where aldosterone plays a key role, including chronic kidney disease and heart failure prevention,” Barr explained in the release.At the same conference, Roche revealed that its midstage hypertension prospect zilebesiran failed a phase 2 study, although the pharma is still planning to take the Alnylam-partnered RNAi therapy into phase 3 later this year.

8月31日，阿斯利康（AstraZeneca）宣布，BaxHTN 3期试验的阳性完整结果显示，与安慰剂相比，难控制（未控制和难治性）高血压患者在标准降压疗法基础上接受baxdrostat两种剂量（2毫克和1毫克）治疗12周时，患者平均坐位收缩压（SBP）均出现具有统计学意义和临床意义的显著降低。相关数据已于8月30日在2025欧洲心脏病学会（ESC）年会的热点研究（Hot Line）专场公布，并同步发表于《新英格兰医学杂志》。 Baxdrostat在BaxHTN 3期试验中达到了主要和全部次要终点，在难控制高血压患者中实现了显著且持久的血压降低。在治疗第12周时，Baxdrostat 2毫克剂量组平均坐位收缩压较基线的绝对降幅为15.7mmHg，经安慰剂校正后的降幅为9.8mmHg。1毫克剂量组平均坐位收缩压的绝对降幅为14.5mmHg，经安慰剂校正后降幅为8.7mmHg。安慰剂组平均坐位收缩压下降5.8mmHg。上述结果在未控制和难治性高血压亚组中表现一致。 Baxdrostat整体耐受性良好，未发现非预期的安全性事件。与安慰剂组（0.0%）相比，Baxdrostat两个剂量组的明确诊断的高钾血症发生率较低（血钾>6 mmol/L，两组均为1.1%）。其安全性特征与作用机制一致，大多数不良事件为轻度。 本试验中，Baxdrostat也达到了所有确认性次要终点。其中，Baxdrostat 2毫克剂量组展现出了持久的长期降压效果。2毫克和1毫克剂量组均实现了更显著的舒张压降低，且患者收缩压＜130mmHg的达标率较安慰剂组提升近三倍。 在一项预设的探索性亚组分析中，baxdrostat相比安慰剂显著降低了患者24小时和夜间动态收缩压，这些均为持续控制血压和降低心血管风险的重要指标。2毫克剂量组可使24小时收缩压降低16.9mmHg（95% CI，–25.6至–8.3），合并分析2毫克和1毫克剂量组后夜间收缩压降幅为11.7mmHg（95% CI，–19.5至–3.8）。评估24小时动态血压控制效果的Bax24 3期试验结果预计将在今年晚些时候公布。 伦敦大学学院医学系主任、首席研究者Bryan Williams博士表示："BaxHTN III期临床试验结果令人振奋，经安慰剂校正后，baxdrostat实现了近10mmHg的收缩压降低，这一降幅有望显著降低心脏病发作、卒中、心力衰竭和肾脏疾病的风险。这些研究数据表明，醛固酮在难控制高血压中的作用比过去所认知的更为重要，凸显了baxdrostat创新作用机制的重要性及其潜在影响力，有望惠及数百万虽已接受多种治疗、但血压仍然难以控制的高血压患者。" 阿斯利康全球执行副总裁，全球生物制药研发负责人Sharon Barr表示："BaxHTN 3期试验结果展示了baxdrostat在应对经多种治疗后仍难以控制的高血压方面的潜力，这是心血管治疗领域最棘手的挑战之一。我们期待在未来数月内推动baxdrostat在多国的注册申报，并在慢性肾脏病、心衰预防等醛固酮发挥关键作用的适应症领域快速推进临床开发项目。" 越来越多证据表明，醛固酮失调是高血压的关键生物学驱动因素之一，可导致患者心血管和肾脏风险升高。一项大型荟萃分析发现，收缩压每降低10mmHg可使主要心血管不良事件风险降低约20%，进一步凸显对以高血压病因为靶点的创新治疗手段的迫切需求。 Baxdrostat为高选择性、强效口服小分子药物，是一种高选择性的醛固酮合成酶抑制剂（ASI），靶向作用于导致血压升高及心血管和肾脏风险增加的激素之一。临床研究表明，baxdrostat 可在较大剂量范围内显著降低醛固酮水平且不影响皮质醇水平目前，该药正在全球范围内开展临床试验，累计入组患者超过20,000人，试验包括作为单药疗法治疗高血压和原发性醛固酮增多症，及与达格列净联用治疗慢性肾脏病和高血压，以及高血压患者预防心力衰竭。 参考资料：[1]Baxdrostat在BaxHTN III期试验中对于难控制高血压患者显示出具有统计学及临床意义的收缩压显著降低. From https://www.prnasia.com/story/501548-1.shtml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。