Will zilebesiran, an RNA interference therapy, be effective, safe, and improve the treatment of hypertension?

IF 3.6 3区 医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Expert Opinion on Biological Therapy Pub Date : 2024-11-06 DOI:10.1080/14712598.2024.2425343
Sheila A Doggrell
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Abstract

Introduction: Less than half of the subjects with hypertension have been diagnosed and treated, with only 21% having their blood pressure under control. Many of the subjects find it difficult to adhere to daily antihypertensives. Zilebesiran reduces hepatic angiotensinogen messenger RNA levels to inhibit the renin-angiotensin-aldosterone system and is being developed as a long-acting anti-hypertensive agent.

Areas covered: KARDIA-1; a phase 2 clinical trial of zilebesiran with mild-to-moderate hypertension. Most doses of zilebesiran (150-600 mg) modestly reduced blood pressure from baseline to month 3. Adverse events included hyperkalemia and kidney failure.

Expert opinion: The main problem with zilebesiran is that it only has a modest effect on blood pressure, and it is likely to have to be used as add-on therapy, which will probably reduce any benefits on adherence it has. It was also difficult to reliably interpret the results of KARDIA-1 as blood pressure went up significantly in the placebo group. KARDIA-1 did not answer previous concerns about zilebesiran; (i) what happens during volume depletion, sepsis, and pregnancy when angiotensinogen is inhibited long term or (ii) will it be effective in a high sodium diet.

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RNA干扰疗法齐来贝西兰是否有效、安全,并能改善高血压的治疗?
导言只有不到一半的高血压患者得到了诊断和治疗,只有 21% 的患者血压得到了控制。许多患者难以坚持每天服用降压药。Zilebesiran 可降低肝脏血管紧张素原信使 RNA 水平,从而抑制肾素-血管紧张素-醛固酮系统,目前正被开发为一种长效抗高血压药物:KARDIA-1;齐来比西兰治疗轻中度高血压的 2 期临床试验。大多数剂量的齐来比西兰(150-600 毫克)都能适度降低从基线到第 3 个月的血压,不良反应包括高钾血症和肾衰竭:齐来贝西然的主要问题是对血压的影响不大,而且很可能必须作为附加疗法使用,这很可能会降低其对依从性的益处。此外,由于安慰剂组的血压明显升高,因此很难可靠地解释 KARDIA-1 的结果。KARDIA-1 并没有回答之前人们对齐来比西兰的担忧:(i) 当血管紧张素原长期受到抑制时,在血容量耗竭、败血症和妊娠期间会发生什么情况;(ii) 在高钠饮食中是否有效。
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来源期刊
Expert Opinion on Biological Therapy
Expert Opinion on Biological Therapy 医学-生物工程与应用微生物
CiteScore
8.60
自引率
0.00%
发文量
96
审稿时长
3-8 weeks
期刊介绍: Expert Opinion on Biological Therapy (1471-2598; 1744-7682) is a MEDLINE-indexed, international journal publishing peer-reviewed research across all aspects of biological therapy. Each article is structured to incorporate the author’s own expert opinion on the impact of the topic on research and clinical practice and the scope for future development. The audience consists of scientists and managers in the healthcare and biopharmaceutical industries and others closely involved in the development and application of biological therapies for the treatment of human disease. The journal welcomes: Reviews covering therapeutic antibodies and vaccines, peptides and proteins, gene therapies and gene transfer technologies, cell-based therapies and regenerative medicine Drug evaluations reviewing the clinical data on a particular biological agent Original research papers reporting the results of clinical investigations on biological agents and biotherapeutic-based studies with a strong link to clinical practice Comprehensive coverage in each review is complemented by the unique Expert Collection format and includes the following sections: Expert Opinion – a personal view of the data presented in the article, a discussion on the developments that are likely to be important in the future, and the avenues of research likely to become exciting as further studies yield more detailed results; Article Highlights – an executive summary of the author’s most critical points.
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