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Medscape
14-07-2025
- Health
- Medscape
Screen All With Hypertension for Primary Aldosteronism
San Francisco — All individuals with hypertension should be screened for primary aldosteronism (PA), according to a new clinical practice guideline from the Endocrine Society. The recommendation is to screen everyone with hypertension by measuring aldosterone and renin and to use the aldosterone to renin ratio to guide clinical care with either medication or surgery. Potassium should also be measured to aid in aldosterone interpretation. Mineralocorticoid receptor antagonists (MRAs) are the preferred medical treatment. The document was posted online July 14, 2025 in the Journal of Clinical Endocrinology and Metabolism and presented on July 15, 2025 at ENDO 2025: The Endocrine Society Annual Meeting. It was endorsed by the American Association of Clinical Endocrinology, American Heart Association, European Society of Endocrinology, European Society of Hypertension, International Society of Hypertension, and the Primary Aldosteronism Foundation. The European Society of Cardiology made a similar recommendation in 2024. PA: Under-Recognized and Under-Treated In PA, the adrenal gland over-produces aldosterone independently of renin, a common phenomenon in the setting of modern-day high-salt diets. This leads to renal sodium retention, volume expansion, and elevated blood pressure, with variable potassium loss. Aldosterone also causes direct damage to the entire cardiorenal system by acting on mineralocorticoid receptors in these target organs. 'If you look at cardiovascular disease in individuals with [PA] as compared to those with primary hypertension, they have an increased risk of stroke, coronary artery disease, atrial fibrillation, heart failure, and renal disease,' the document's lead author, Gail K. Adler, MD, PhD, chief of the cardiovascular endocrinology section at Brigham and Women's Hospital, Boston, Massachusetts, told Medscape Medical News . The condition can be lateralizing, typically caused by an adrenal adenoma that can be surgically removed, or bilateral, commonly resulting from multiple adrenal microadenomas, for which MRAs are effective treatment. Currently, PA is vastly under-recognized and under-treated. Studies conducted over the past couple of decades suggest that PA prevalence is 5.9% among people with hypertension seen in primary care, 16.2% of younger adults aged 18-40 years with hypertension, 28.1% among adults with both hypertension and hypokalemia, 42% of those with hypertension and atrial fibrillation, and between 11.3% and 19.1% of those with hypertension and type 2 diabetes, according to the document. Yet, in a study of US Veterans published in 2020, PA screening rates were less than 2% even among those with treatment-resistant hypertension. No improvements in screening rates were found in a more recent follow-up study from the same team. Meta-analyses have shown that, compared to people with primary hypertension, those with PA have more than twice the risk for stroke and kidney disease, more than triple for atrial fibrillation, and twice the risk for heart failure. The goal of this new guideline, Adler said, 'is to make it easy to diagnose [PA] and to start appropriate aldosterone-targeted therapy to reduce the excess cardiovascular, stroke, and renal morbidity associated with [PA]. It's so easy to treat. Part of the problem in the past is we made it so hard to diagnose.' Universal screening of people with hypertension for PA is already common practice in Japan, Australia, and China, where studies have demonstrated cost-effectiveness derived from the reduction in long-term complications, the authors point out. The Recommendations The Endocrine Society makes ten conditional recommendations all worded as 'we suggest' based on the low level of evidence per the Grading of Recommendations Assessment, Development and Evaluations Evidence to Decision framework. PA screening is suggested in all individuals with hypertension. In individuals with hypertension and PA, PA-specific therapy is suggested. Medical treatment with MRAs is preferable to nonspecific antihypertensive therapy. For individuals with lateralizing PA who are surgical candidates and desire surgery, unilateral adrenalectomy is preferred. Screening for PA should include measurements of serum/plasma aldosterone concentration and plasma renin (concentration or activity). A positive screen is defined as both a low renin level with inappropriately high aldosterone and an elevated aldosterone to renin ratio. Cutoffs for both values differ by assay and are provided in the document. Potassium should be measured with aldosterone to aid in interpretation since low potassium can lead to falsely low aldosterone readings. Management of interfering medications depends on individual safety and feasibility. The document provides strategies for both minimal withdrawal and no-withdrawal prior to screening. 'Before, we said stop all antihypertensives. It was so difficult. Now we say just test them,' Adler commented. In individuals who screen positive for PA, aldosterone suppression testing is suggested in situations where screening results indicate an intermediate probability of lateralizing PA and the patient desires surgery. In individuals with PA, medical or surgical therapy is suggested, with the choice based on lateralization of aldosterone hypersecretion and candidacy for surgery. For those with PA considering surgery, computed tomography scanning and adrenal venous sampling are suggested prior to deciding on the treatment approach. For individuals with PA in whom hypertension is not controlled and renin is suppressed despite PA-specific medical therapy, a dose increase is suggested to raise renin levels. For those with PA and adrenal adenoma, a dexamethasone suppression test is suggested. In individuals with PA receiving PA-specific medical therapy, spironolactone is preferred over other MRAs due to its low cost and widespread availability. For those with PA receiving PA-specific medical therapy, MRAs are preferred rather than epithelial sodium-channel inhibitors (amiloride, triamterene). Asked to comment, Jordana Cohen, MD, associate professor of medicine and epidemiology at the Perelman School of Medicine, University of Pennsylvania, Philadelphia, told Medscape Medical News , 'We do a very poor job of screening for PA and, as a result, it is being missed in the vast majority of cases. More people are screened for pheochromocytoma, even though it's far rarer, than for [PA]. This really needs to change. I think the new guidelines are an important step toward simplifying and removing barriers to screening that have the potential to improve screening rates, assuming they are implemented.' Cohen, who led the veterans affairs (VA) studies that found the extremely low PA screening rates, added that — in contrast to previous PA guidelines — this one 'does a great job of providing guidance about no longer holding medications in most cases — based on growing evidence to support this — how to interpret the results, and when further testing may be needed.' Also asked to comment, Richard J. Auchus, MD, chief of the Endocrinology & Metabolism Section at the Ann Arbor VA Medical Center, Michigan, told Medscape Medical News he generally supports the guideline, while also expressing some caveats about universally screening everyone with hypertension. 'I definitely agree with screening everyone who fails two antihypertensive drugs. Nobody on the planet is going to argue that patients with difficult-to-control hypertension shouldn't be screened. And the truth is that about two-thirds of people with hypertension are not controlled, and many are already taking two drugs. I don't disagree with the guidelines, but I do think there are some people, like a 70-year-old newly diagnosed with hypertension who you put on 12.5 mg of hydrochlorothiazide and now their blood pressure is normal, who might not need to be screened. If we screen everybody, it's going to add to the cost of healthcare in the short-term, but maybe not in the long-term.' 'I can see both sides,' Auchus added. 'We want to catch people early on to minimize the end organ damage from being on the wrong drug. So, I think the risk benefit ratio is probably in favor of screening everybody.' Adler receives research funding from the National Institutes of Health and Tersus Life Sciences, LLC. Auchus and Cohen have no relevant disclosures.
Associated Press
30-06-2025
- Business
- Associated Press
Mineralys Therapeutics Announces Journal of the American Medical Association (JAMA) Publication of Pivotal Phase 3 Launch-HTN Trial for Lorundrostat
– The Launch-HTN trial is the largest trial of an aldosterone synthase inhibitor completed in participants with uncontrolled or treatment resistant hypertension – –Lorundrostat 50 mg once daily demonstrated clinically meaningful reductions in systolic blood pressure, with a 16.9 mmHg reduction at Week 6 and a 19.0 mmHg reduction at Week 12– –Lorundrostat was generally well-tolerated; and treatment-emergent adverse events were mostly mild, transient, and resolved without intervention – RADNOR, Pa., June 30, 2025 (GLOBE NEWSWIRE) -- Mineralys Therapeutics, Inc. (Nasdaq: MLYS), a clinical-stage biopharmaceutical company focused on developing medicines to target hypertension, chronic kidney disease (CKD), obstructive sleep apnea (OSA) and other diseases driven by dysregulated aldosterone, today announced the publication of the positive results from the pivotal Phase 3 Launch-HTN trial in the Journal of the American Medical Association (JAMA). The manuscript titled 'Lorundrostat in Participants with Uncontrolled and Treatment-Resistant Hypertension' is featured in the June 30, 2025 issue. The Launch-HTN trial evaluated the efficacy and safety of lorundrostat, a novel aldosterone synthase inhibitor (ASI), when added to existing background treatment in 1,083 participants with uncontrolled or treatment resistant hypertension. The trial demonstrated that lorundrostat significantly reduced systolic blood pressure (BP) with a favorable safety and tolerability profile. 'Hypertension remains the most prevalent and preventable driver of cardiovascular disease globally, yet a significant proportion of patients continue to struggle with inadequate blood pressure control. We believe lorundrostat has the potential to be a best-in-class treatment for patients with uncontrolled or treatment resistant hypertension,' said Jon Congleton, Chief Executive Officer of Mineralys Therapeutics. 'We are pleased to have the results of Launch-HTN published in a medical journal as prestigious as JAMA. The consistency of results seen in the lorundrostat development program – which includes multiple trials across differentiated patient populations – supports its potential to have a broad role in future hypertension care.' 'Launch-HTN was the largest Phase 3 trial of an ASI in patients with uncontrolled or resistant hypertension, designed to reflect usual clinical practice. It demonstrated consistent blood pressure lowering efficacy and safety with the aldosterone synthase inhibitor, lorundrostat, across a diverse group of patients,' said Dr. Manish Saxena, MBBS, Deputy Clinical Co-Director of Queen Mary University of London's William Harvey Heart Centre, and Hypertension Specialist at Barts Health NHS Trust and lead investigator on the study. 'Dysregulated aldosterone, a key factor in driving hypertension in up to 30% of all hypertensive patients, is a consistent feature of treatment-resistant hypertension and related cardiovascular morbidities, such as heart failure and chronic kidney disease, making aldosterone synthase inhibition an attractive treatment target. Lorundrostat, a novel ASI therapy, is a promising development that could help address unmet clinical needs for patients who remain hypertensive despite multiple medications.' Key Findings from Launch-HTN The Launch-HTN trial was a global, randomized, double-blinded, placebo-controlled Phase 3 trial, which enrolled 1,083 eligible adult participants who failed to achieve their BP goal despite being on two to five antihypertensive medications. Launch-HTN reflects the real-world setting for clinicians by utilizing automated office blood pressure (AOBP) measurements and allowing participants to stay on their existing medications. Authors noted that the trial recruited a diverse population as reflected in the high proportion of females, Black or African American and elderly participants. When added to existing background treatment, lorundrostat 50 mg dosed once daily demonstrated clinically meaningful, statistically significant mean reductions in AOBP with a 16.9 mmHg reduction at Week 6 (-9.1 mmHg placebo adjusted; p-value < 0.0001) that was sustained with a reduction of 19.0 mmHg at Week 12 (-11.7 mmHg placebo adjusted; p-value < 0.0001). These benefits were consistent across age, sex, race, body mass index, and baseline medication regimen. Lorundrostat demonstrated a favorable safety and tolerability profile in the Launch-HTN trial. The anticipated on-target effects on serum electrolytes, increased serum potassium and reduced serum sodium were modest and rapidly reversible upon discontinuation of lorundrostat. A confirmed serum potassium level of greater than 6.0 mmol/L occurred in three subjects (0.6%) on lorundrostat 50 mg once daily, as compared to one subject (0.4%) on placebo. Suppression of cortisol production was not observed, and there was a very low incidence of drug-related serious adverse events resulting in discontinuation or dose-adjustment of study medication. About Hypertension Having sustained, elevated BP (or hypertension) increases the risk of heart disease, heart attack and stroke, which are leading causes of death in the United States.1 In 2022, more than 685,000 deaths in the United States included hypertension as a primary or contributing cause.2 Hypertension and related health issues resulted in an estimated annual economic burden of about $219 billion in the United States in 2019.3 Less than 50% of hypertension patients achieve their BP goal with currently available medications.4 Dysregulated aldosterone levels are a key factor in driving hypertension in approximately 30% of all hypertensive patients.5 About Lorundrostat Lorundrostat is a proprietary, orally administered, highly selective aldosterone synthase inhibitor being developed for the treatment of uncontrolled hypertension (uHTN) or resistant hypertension (rHTN), as well as CKD and OSA. Lorundrostat was designed to reduce aldosterone levels by inhibiting CYP11B2, the enzyme responsible for its production. Lorundrostat has 374-fold selectivity for aldosterone-synthase inhibition versus cortisol-synthase inhibition in vitro, an observed half-life of 10-12 hours and demonstrated a 40-70% reduction in plasma aldosterone concentration in hypertensive subjects. About Mineralys Therapeutics Mineralys Therapeutics is a clinical-stage biopharmaceutical company focused on developing medicines to target hypertension, CKD, OSA and other diseases driven by dysregulated aldosterone. Its initial product candidate, lorundrostat, is a proprietary, orally administered, highly selective aldosterone synthase inhibitor that Mineralys Therapeutics is developing for the treatment of cardiorenal conditions affected by dysregulated aldosterone, including hypertension, CKD, and OSA. Mineralys is based in Radnor, Pennsylvania, and was founded by Catalys Pacific. For more information, please visit Follow Mineralys on LinkedIn, Twitter and Bluesky. Forward Looking Statements Mineralys Therapeutics cautions you that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. The forward-looking statements are based on our current beliefs and expectations and include, but are not limited to, statements regarding: the potential therapeutic benefits of lorundrostat; the Company's expectation that ASIs with an SGLT2 inhibitor may provide additive clinical benefits to patients; the Company's expectation that Advance-HTN and Launch-HTN may serve as pivotal trials in submission of a new drug application (NDA) to the U.S. Food and Drug Administration (FDA); the Company's ability to evaluate lorundrostat as a potential treatment for CKD, OSA, uHTN or rHTN; the planned future clinical development of lorundrostat and the timing thereof; and the expected timing of commencement and enrollment of participants in clinical trials and topline results from clinical trials. Actual results may differ from those set forth in this press release due to the risks and uncertainties inherent in our business, including, without limitation: topline results that we report are based on a preliminary analysis of key efficacy and safety data, and such data may change following a more comprehensive review of the data related to the clinical trial and such topline data may not accurately reflect the complete results of a clinical trial; our future performance is dependent entirely on the success of lorundrostat; potential delays in the commencement, enrollment and completion of clinical trials and nonclinical studies; later developments with the FDA may be inconsistent with the feedback from the completed end of Phase 2 meeting, including whether the proposed pivotal program will support registration of lorundrostat which is a review issue with the FDA upon submission of an NDA; the results of our clinical trials, including the Advance-HTN and Launch-HTN trials, may not be deemed sufficient by the FDA to serve as the basis for an NDA submission or regulatory approval of lorundrostat; our dependence on third parties in connection with manufacturing, research and clinical and nonclinical testing; unexpected adverse side effects or inadequate efficacy of lorundrostat that may limit its development, regulatory approval and/or commercialization; unfavorable results from clinical trials and nonclinical studies; results of prior clinical trials and studies of lorundrostat are not necessarily predictive of future results; macroeconomic trends and uncertainty with regard to high interest rates, elevated inflation, tariffs, and the potential for a local and/or global economic recession; our ability to maintain undisrupted business operations due to any pandemic or future public health concerns; regulatory developments in the United States and foreign countries; our reliance on our exclusive license with Mitsubishi Tanabe Pharma to provide us with intellectual property rights to develop and commercialize lorundrostat; and other risks described in our filings with the Securities and Exchange Commission (SEC), including under the heading 'Risk Factors' in our annual report on Form 10-K, and any subsequent filings with the SEC. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and we undertake no obligation to update such statements to reflect events that occur or circumstances that exist after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. References 1 CDC. Facts About Hypertension. Centers for Disease Control and Prevention. Updated September 27, 2023. Accessed June 2025. 2 CDC. Underlying Cause of Death, 1999–2022 Results. CDC WONDER Online Database. Accessed June 2025. 3 Centers for Disease Control and Prevention. Health and Economic Benefits of High Blood Pressure Interventions. National Center for Chronic Disease Prevention and Health Promotion. Updated November 20, 2023. Accessed June 2025. 4 Carey RM, et al. Resistant Hypertension: Detection, Evaluation, and Management: A Scientific Statement from the AHA. Hypertension. 2018;72(5):e53-e90. 5 Brown JM, et al. Primary Aldosteronism and the Pathogenesis of Hypertension. Physiol Rev. 2018;98(1):103-137. Contact: Investor Relations [email protected] Media Relations Melyssa Weible Elixir Health Public Relations Phone:1-201-723-5805 Email: [email protected]
Medical News Today
02-06-2025
- Business
- Medical News Today
Hypertension: New drug shows strong results in managing blood pressure
A clinical trial has seen promising results from a new class of medication to treat hypertension. Design by MNT; Photography by Peca King/500px/Getty Images & MementoJpeg/Getty Images A novel treatment for hard-to-control high blood pressure has shown strong results in a major global clinical trial. The Phase 3 Launch-HTN study found that lorundrostat, an aldosterone synthase inhibitor, safely and consistently lowered blood pressure in a large, diverse group of patients who had not responded to other medications. These findings mark a significant step forward in the development of the first targeted aldosterone synthase inhibitor for these conditions. Blood pressure refers to the force exerted by blood against the walls of the arteries. Hypertension, or high blood pressure, happens when this force is consistently higher than normal. Hypertension impacts one in three adults globally and significantly raises the risk of heart disease, heart attacks, and strokes. Resistant hypertension is a form of high blood pressure that remains elevated despite a person taking three different blood pressure medications at their maximum recommended doses. Up to 15% of individuals with hypertension have abnormal regulation of aldosterone, a hormone that helps control blood pressure. When aldosterone levels are elevated due to this dysregulation, it can lead to hypertension. A new study, presented at the 34th European Meeting on Hypertension and Cardiovascular Protection, shows that lorundrostat — a drug that inhibits aldosterone synthase — is both safe and effective for treating individuals with uncontrolled or resistant hypertension. The findings are yet to be published in a peer-reviewed journal. Lorundrostat is specifically designed to lower aldosterone levels by targeting and inhibiting CYP11B2, the enzyme that drives its production. The study demonstrated consistent reductions in blood pressure across a large and diverse group of patients and represents the largest phase three trial to date for this class of treatment. Manish Saxena, MD, Clinical Co-Director of the William Harvey Heart Centre at Queen Mary University of London and Hypertension Specialist from Barts Health NHS Trust and the study's lead Investigator, spoke to Medical News Today . 'Despite available treatments, more than 40% of adults with hypertension worldwide are not reaching their blood pressure goal. Aldosterone pathway plays important role in blood pressure regulation, and leads to blood pressure related complications such as heart failure and kidney problems. In the Launch-HTN trial we explored the safety and effectiveness of lorundostat, which belongs to a new class of drugs called aldosterone synthase inhibitors that block production of hormone aldosterone from the adrenal glands.' — Manish Saxena, MD 'The Launch-HTN trial is the largest phase 3 hypertension study with a novel drug,' Saxena explained. 'We tested lorundostat in a large, diverse patient population recruited globally and found that it has good safety profile and lowered blood pressure consistently in all of our patient groups.' How lorundrostat works 'Hormone aldosterone secreted from adrenal glands in the body plays an important role in driving blood pressure. Now there is more awareness of dysregulated aldosterone secretion in patients with difficult to treat blood pressure. Lorundrostat blocks biosynthesis of hormone aldosterone in the body and helps reduce blood pressure.' — Manish Saxena, MD The Launch-HTN trial was a global, Phase 3 study that was randomized, double-blind, and placebo-controlled. It included adult participants whose blood pressure remained uncontrolled despite taking two to five antihypertensive medications. Designed to reflect real-world clinical practice, the trial used automated office blood pressure (AOBP) measurements and allowed participants to continue their existing treatments. Lorundrostat, administered once daily at a 50 mg dose, showed meaningful and sustained reductions in systolic blood pressure — dropping by 16.9 mmHg at Week 6 (a 9.1 mmHg reduction compared to placebo) and by 19 mmHg at Week 12 (an 11.7 mmHg reduction versus placebo). 'The LAUNCH-HTN trial demonstrated blood pressure lowering efficacy and safety of lorundrostat in a very diverse patient group with uncontrolled and difficult to treat hypertension that were on background 2-5 blood pressure lowering medication. The blood pressure reduction observed was consistent across key sub-groups, significant and clinically meaningful.' — Manish Saxena, MD Two experts, not involved in the study, also spoke to MNT . Cheng-Han Chen, MD, board certified interventional cardiologist and medical director of the Structural Heart Program at MemorialCare Saddleback Medical Center in Laguna Hills, CA, noted that 'aldosterone synthase inhibitors are a new class of drugs being studied for the treatment of hypertension.' 'This trial found that lorundrostat, one of these new types of drugs, was safe and effective for patients with uncontrolled or resistant hypertension. This puts us one step closer to having another tool in our arsenal for patients with difficult to control blood pressure despite being on multiple medications,' Chen explained. 'Many patients have high blood pressure that are not under control with multiple classes of medications. By having another class of blood pressure medications at our disposal, we will better be able to reduce rates of hypertension in our population and improve health outcomes.' — Cheng-Han Chen, MD Rigved Tadwalkar, MD, FACC, consultative cardiologist and director of Digital Transformation Pacific Heart Institute in Santa Monica, CA told MNT that 'this is a meaningful step forward.' 'We still see far too many patients with uncontrolled or resistant hypertension, even when they're on three, four, sometimes five medications. The reality is that for a significant subset of these patients, aldosterone is driving the problem and until now, we haven't had a way to target that mechanism directly in a safe, practical way,' Tadwalkar explained. 'Lorundrostat appears to change that. It inhibits aldosterone synthesis at the enzymatic level, and based on this trial, it does so with a good safety profile and consistent efficacy across a diverse population. The blood pressure reductions– nearly 17 mmHg at 6 weeks and close to 19 mmHg at 12– are significant, especially when you consider that these were already heavily treated patients. That kind of additional drop is not something we usually see at this stage of therapy.' — Rigved Tadwalkar, MD, FACC 'Since patients stayed on their background medications, these results feel more clinically relevant than more tightly controlled washout studies,' Tadwalkar added. 'It's a welcome addition to the field, even as we continue to see the limitations of existing therapies, including newer device-based approaches like renal denervation.' Tadwalkar said that lorundrostat had potential to make a real difference in patients' lives. 'If lorundrostat becomes widely available, it could offer a new option for patients who've exhausted standard pathways. For people living with resistant hypertension, many of whom are already dealing with co-morbidities like kidney disease or heart failure, having another tool, especially one that targets the underlying hormonal dysregulation, could make a real difference in long-term outcomes,' he said. Saxena said that once lorundostat becomes commercially available, it could become a novel treatment option for hypertension for many patients. Tadwalkar continued by noting that 'at the population level, we're still facing a huge burden from poorly controlled blood pressure.' He said untreated hypertension was a major contributor to chronic diseases and cardiovascular problems. 'A drug like this, if used properly, could help narrow that treatment gap. It's certainly not a silver bullet, but it's a step toward more personalized, mechanism-specific care. This is something the hypertension field has needed for a long time.' — Rigved Tadwalkar, MD, FACC Hypertension Clinical Trials / Drug Trials Drugs
