baxdrostat (CIN-107) / Roche, AstraZeneca - LARVOL DELTA

BaxHTN – Efficacy and safety of the aldosterone synthase inhibitor baxdrostat in patients with uncontrolled or resistant hypertension (ESC-WCC 2025) - No abstract available

Clinical • Cardiovascular • Hypertension

AstraZeneca plans to invest $50 billion in America for medicines manufacturing and R&D (AstraZeneca Press Release) - "AstraZeneca today announces $50 billion of investment in the United States by 2030, building on America’s global leadership in medicines manufacturing and R&D. This investment is expected to create tens of thousands of new, highly skilled direct and indirect jobs across the country powering growth and delivering next generation medicines for patients in America and worldwide. The cornerstone of this landmark investment is a new multi-billion dollar US manufacturing facility that will produce drug substances for the Company’s innovative weight management and metabolic portfolio, including oral GLP-1, baxdrostat, oral PCSK9 and combination small molecule products. The new state-of-the-art centre will produce small molecules, peptides and oligonucleotides. This multi-billion dollar capital investment is in addition to the $3.5 billion announced in November 2024."

Commercial • Metabolic Disorders • Obesity

Blood Pressure-Lowering Effects of Aldosterone Synthase Inhibitors-A Systematic Review. (PubMed, Basic Clin Pharmacol Toxicol) - "A significant suppression of cortisol production was found for LCI699 (osilodrostat) but not for baxdrostat, lorundrostat, BI 690517 (vicadrostat) or dexfadrostat. We conclude that ASIs have promising BP-lowering effects with very limited effects on cortisol production and offer reno-protective effects in chronic kidney disease. Studies on hypertensive target organ damage and cardiovascular outcomes are, however, lacking."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Fibrosis • Hypertension • Immunology • Nephrology • Novel Coronavirus Disease • Renal Disease

Baxdrostat in Patients with Primary Aldosteronism: Results from the SPARK Phase 2 Trial (ENDO 2025) - P2 | "Baxdrostat, an ASI, was well tolerated and led to reduced BP and unsuppressed renin in patients with PA. Inhibiting aldosterone synthase may be an alternative to MRAs for treating PA."

Clinical • P2 data • Endocrine Disorders • Hypotension

In Vitro Study of the Effects of the Novel Aldosterone Synthase Inhibitor Baxdrostat (ENDO 2025) - "Bax, Osilodrostat (Osi), and Metyrapone (Met) were added to the culture medium at concentrations ranging from 0.0001 to 10 μM. In APA cells, the IC50 of Bax for Ald was 0.063 μM, with Osi (0.003 μM) and Met (1.310 μM) showing dose-dependent inhibitory effects. In CPT cells, Bax exhibited a weaker inhibitory effect on F compared to Osi (IC50: 0.438 μM) and Met (0.748 μM). Bax induced a concentration-dependent increase in 11-deoxycorticosterone (DOC) in APA cells, though the increase was lower than that observed with Osi."

Preclinical • Adrenal Cortex Carcinoma • Cardiovascular • Endocrine Cancer • Endocrine Disorders • Hypertension • Oncology • Solid Tumor • CYP11B1

Phase 2a Study of Baxdrostat in Primary Aldosteronism. (PubMed, N Engl J Med) - No abstract available

Journal • P2a data • Endocrine Disorders

BaxAsia: A Study to Investigate the Efficacy and Safety of Baxdrostat in Participants With Uncontrolled Hypertension on Two or More Medications Including Participants With Resistant Hypertension (clinicaltrials.gov) - P3 | N=326 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting | Trial primary completion date: May 2026 ➔ Nov 2025

Enrollment closed • Trial primary completion date • Cardiovascular • Hypertension

BaxPA: A Study to Assess Efficacy and Safety of Baxdrostat in Participants With Primary Aldosteronism (clinicaltrials.gov) - P3 | N=180 | Not yet recruiting | Sponsor: AstraZeneca

New P3 trial • Endocrine Disorders

Breaking down resistance: novel aldosterone synthase inhibitors in the management of resistant hypertension. (PubMed, J Hypertens) - "The review highlights clinical trial evidence to-date for all agents in this class, with a key focus on the two most mature agents baxdrostat and lorundrostat which are currently in pivotal Phase 3 trials. They have also shown promise with marked blood pressure reductions in patients with varying physiological profiles and few adverse events at optimised doses. However, as would be expected, both drugs are associated with increases in serum potassium levels, necessitating careful monitoring."

Journal • Cardiovascular • Chronic Kidney Disease • Hypertension • Nephrology • Renal Disease

Prediction of pharmacokinetic/pharmacodynamic properties of aldosterone synthase inhibitors at drug discovery stage using an artificial intelligence-physiologically based pharmacokinetic model. (PubMed, Front Pharmacol) - "Following calibration and validation using published data, the model was applied to estimate the PK parameters of Baxdrostat, Dexfadrostat, Lorundrostat, BI689648, and the 11β-hydroxylase inhibitor LCI699. The results demonstrated that the PK/PD properties of an ASI could be inferred from its structural formula within a certain error range, providing a reference for early ASI lead compounds screening and optimization. Further validation and refinement of this model will enhance its predictive accuracy and expand its application in drug discovery."

Journal • PK/PD data

Bax24: A Study to Investigate the Effect of Baxdrostat on Ambulatory Blood Pressure in Participants With Resistant Hypertension (clinicaltrials.gov) - P3 | N=217 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • Cardiovascular • Hypertension

Novel approaches in antihypertensive pharmacotherapeutics. (PubMed, Curr Opin Nephrol Hypertens) - "Pharmacotherapeutic management options for hypertension is a growing field of research with potential clinical implications for multiple agents in upcoming years. Such novel approaches have the potential to improve clinical outcomes of hypertension management."

Journal • Cardiovascular • Hypertension

Prevent-HF: Phase III Study Investigating Heart Failure and Cardiovascular Death With Baxdrostat in Combination With Dapagliflozin (clinicaltrials.gov) - P3 | N=11300 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Congestive Heart Failure • Heart Failure

BaxDuo-Pacific: A Phase III Renal Outcomes and Cardiovascular Mortality Study to Investigate the Efficacy and Safety of Baxdrostat in Combination With Dapagliflozin in Participants With Chronic Kidney Disease and High Blood Pressure (clinicaltrials.gov) - P3 | N=5000 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Chronic Kidney Disease • Hypertension • Nephrology • Renal Disease

Targeting aldosterone to improve cardiorenal outcomes: from nonsteroidal mineralocorticoid receptor antagonists to aldosterone synthase inhibitors. (PubMed, Curr Opin Nephrol Hypertens) - "In the coming years, nonsteroidal MR antagonists and aldosterone synthase inhibitors are likely to play an increasingly large role in routine medical practice to help improve cardiovascular and kidney outcomes."

Journal • Cardiovascular • Chronic Kidney Disease • Hypertension • Nephrology • Renal Disease

A Study to Investigate the Pharmacokinetics of Ethinyl Estradiol and Levonorgestrel When Given Alone and in Combination With Baxdrostat in Healthy Females of Non-childbearing Potential (clinicaltrials.gov) - P1 | N=22 | Completed | Sponsor: AstraZeneca | Active, not recruiting ➔ Completed

Trial completion

BaxHTN: A Study to Investigate the Efficacy and Safety of Baxdrostat in Participants With Uncontrolled Hypertension on Two or More Medications Including Participants With Resistant Hypertension (clinicaltrials.gov) - P3 | N=777 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • Cardiovascular • Hypertension

spark-PA: A Study of CIN-107 in Adults With Primary Aldosteronism (clinicaltrials.gov) - P2 | N=15 | Completed | Sponsor: AstraZeneca | Active, not recruiting ➔ Completed

Trial completion • Endocrine Disorders

A Study to Investigate the Pharmacokinetics of Ethinyl Estradiol and Levonorgestrel When Given Alone and in Combination With Baxdrostat in Healthy Females of Non-childbearing Potential (clinicaltrials.gov) - P1 | N=22 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting | N=48 ➔ 22

Enrollment change • Enrollment closed

Novel pharmacologic approaches in resistant hypertension. (PubMed, Wiad Lek) - "Recently, valsartan/sacubitrol and flozins have been increasingly used in resistant hypertension, which have been introduced for the treatment of diseases other than hypertension but can be a supplement to previously used drugs in resistant hypertension...The results to date allow for the consideration of aprocitentan (a drug that inhibits endothelin receptors) or baxdrostat or another new aldosterone synthesis inhibitor in the treatment of resistant hypertension that does not respond to 4 drugs, including spironolactone. Further studies are needed to confirm the efficacy and safety of these new drugs in the treatment of resistant hypertension."

Journal • Review • Cardiovascular • Hypertension

BaxHTN: A Study to Investigate the Efficacy and Safety of Baxdrostat in Participants With Uncontrolled Hypertension on Two or More Medications Including Participants With Resistant Hypertension (clinicaltrials.gov) - P3 | N=720 | Recruiting | Sponsor: AstraZeneca | Trial primary completion date: Oct 2025 ➔ Jun 2025

Trial primary completion date • Cardiovascular • Hypertension

BaxDuo-Pacific: A Phase III Renal Outcomes and Cardiovascular Mortality Study to Investigate the Efficacy and Safety of Baxdrostat in Combination With Dapagliflozin in Participants With Chronic Kidney Disease and High Blood Pressure (clinicaltrials.gov) - P3 | N=5000 | Not yet recruiting | Sponsor: AstraZeneca

New P3 trial • Cardiovascular • Chronic Kidney Disease • Hypertension • Nephrology • Renal Disease

A Study to Evaluate Cortisol Reserve in Response to Adrenocorticotropic Hormone (ACTH) Stimulation Test Following Baxdrostat Treatment Compared to Placebo in Participants With Uncontrolled Hypertension (clinicaltrials.gov) - P2 | N=48 | Completed | Sponsor: AstraZeneca | Active, not recruiting ➔ Completed

Trial completion • Cardiovascular • Hypertension

A Study to Investigate the Pharmacokinetics of Ethinyl Estradiol and Levonorgestrel When Given Alone and in Combination With Baxdrostat in Healthy Females of Non-childbearing Potential (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open

Effect of Baxdrostat on Albuminuria in Treatment-Resistant Hypertension (KIDNEY WEEK 2024) - P3 | "In a placebo-controlled trial of baxdrostat for resistant hypertension, baxdrostat 2 mg daily reduced UACR. Relatively few BrigHTN participants had CKD, and any amount of albuminuria was allowed. The phase 3 Arctic trial (NCT06268873) of patients with CKD and hypertension will compare baxdrostat/dapagliflozin to placebo/dapagliflozin both on top of maximally tolerated ACE inhibitors or angiotensin receptor blockers to assess the primary endpoint of change in eGFR over time."

Cardiovascular • Chronic Kidney Disease • Hypertension • Renal Disease