AstraZeneca Initiates Phase 3 Trial in China for Baxdrostat, a First-in-Class Aldosterone Synthase Inhibitor, in Resistant Hypertension

▎WuXi AppTec Content Team Report

China Drug Clinical Trial Registration and Information Disclosure Website recently disclosed that AstraZeneca has launched an international multi-center (including China) Phase 3 clinical study in China, aiming toReceiving two or more drug treatments and uncontrolledAsian Hypertensive Subjects (Including Resistant Hypertensive Subjects)Evaluation of the Efficacy and Safety of Baxdrostat, a Novel Class 1 Drug.Baxdrostat isAn Aldosterone Synthase Inhibitor (ASI), initially developed by CinCor Pharma. In 2023, AstraZeneca acquired baxdrostat through the acquisition of CinCor Pharma to expand its pipeline of products under development in the cardio-renal disease area.

Screenshot source:China Drug Clinical Trial Registration and Information Disclosure Platform Official Website

Hypertension is one of the leading causes of morbidity and mortality from cardiovascular diseases worldwide."Refractory Hypertension"It refers to patients who, on the basis of lifestyle improvements, use three different types of antihypertensive drugs in combination, with each drug reaching its maximum dose, but their blood pressure still cannot be controlled, or those who need to use at least four or more drugs to achieve the target blood pressure. Data shows,In patients with hypertension treated with medication, 5% to 30% have resistant hypertension., there remains a significant unmet medical need for such patients.

Studies show that approximately 20% of patients with refractory hypertension have elevated aldosterone levels, which are positively correlated with increased blood pressure. The reason may be that aldosterone promotes water and sodium retention, inflammation, arteriosclerosis, and oxidative stress, further contributing to the formation of refractory hypertension. Therefore, over the past decade,Inhibition of aldosterone synthase to reduce aldosterone synthesis has been a drug target for the treatment of hypertension.。

Baxdrostat (CIN-107) is a novel aldosterone synthase inhibitor (ASI)., itsOptionally targets byCYP11B2The gene-encoded aldosterone synthase, as well as 11ß-hydroxylase (the enzyme responsible for cortisol synthesis, encoded byCYP11B1Much lower affinity for blocking activity of gene coding.

AstraZenecaAs previously noted in the press release,Baxdrostat represents a potentially leading next-generation ASI because it is highly selective for aldosterone synthase and preserves the cortisol pathway in the human body.。In preclinical and Phase 1 studies, baxdrostatYesAldosterone SynthaseInhibition showed a selectivity of 100:1, and multiple dose levels of baxdrostat reduced plasma aldosterone levels without reducing cortisol levels.。

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AstraZeneca has initiated a double-blind, randomized, placebo-controlled, multi-center study (BaxAsia study). The aim of this study is to evaluate approximately 300 patients who are on a stable treatment regimen of two antihypertensive drugs or ≥3 antihypertensive drugs at baseline and are aged ≥18 years.Asian Hypertensive SubjectsMid-term evaluation of 1mg or 2mg of BaxdrostatOnce dailyOral administration compared with placebo in reducingSystolic Blood Pressure (SBP)in terms of safety, tolerability, and efficacy. The principal investigator in China for this study is Ruijin Hospital, affiliated with Shanghai Jiao Tong University School of Medicine.Dr. Wang Jiguang, Chief Physician。

Notably, in February 2023, researchers in"The New England Journal of Medicine" (NEJM`) Published Phase 2 clinical trial data of baxdrostat for the treatment of patients with refractory hypertension. The study results show:`Baxdrostat treatment led to a dose-related reduction in blood pressure in patients with resistant hypertension.。

In addition to targeting refractory hypertension,Baxdrostat is also expected to be used for the treatment ofPrimary Aldosteronism (Spark-PA)AndChronic Kidney Disease (CKD) with HypertensionPatients, relevant phase 2 or phase 3 clinical studies are ongoing.In addition, the drug also has the potential to be used in combination with AstraZeneca's SGLT2 inhibitor dapagliflozin to further address the significant unmet medical needs in the field of cardiology and nephrology.

References:

[1] ChinaClinical Trial Registry and Information Disclosure Platform Official Website. Retrieved Mar 21, 2024. From http://www.chinadrugtrials.org.cn/clinicaltrials.searchlist.dhtml

[2] Acquisition of CinCor Pharma complete. Retrieved 2023-02-24, from https://www.astrazeneca.com/media-centre/press-releases/2023/astrazeneca-acquires-cincor-for-cardiorenal-asset.html

[3] Williams B. A New Dawn for Aldosterone as a Therapeutic Target in Hypertension.JAMA. Published online September 10, 2023. doi:10.1001/jama.2023.17087
[4]Mason W. Freeman, Yuan-Di Halvorsen, et al.(2023)Phase 2 Trial of Baxdrostat for Treatment-Resistant Hypertension. N Engl J Med.DOI: 10.1056/NEJMoa2213169