Mineralys Therapeutics Announces Late-Breaking Data from Advance-HTN Pivotal Trial of Lorundrostat in Uncontrolled and Resistant Hypertension Presented at the American College of Cardiology’s Annual Scientific Session & Expo (ACC.25)
Mineralys Therapeutics (NASDAQ: MLYS) announced detailed results from its Phase 2 Advance-HTN pivotal trial evaluating lorundrostat for uncontrolled and resistant hypertension. The trial demonstrated that lorundrostat 50 mg achieved a 15.4 mmHg absolute reduction and 7.9 mmHg placebo-adjusted reduction (p=0.001) in blood pressure at week 12.
The study showed a favorable safety profile with modest changes in potassium, sodium, and eGFR levels. The trial included a diverse patient population, with 40% women and 53% Black participants. Serious adverse events occurred in 6%, 8%, and 2% of patients in the lorundrostat 50 mg, 50-100 mg, and placebo arms respectively.
Lorundrostat functions as a highly selective aldosterone synthase inhibitor, targeting hypertension, chronic kidney disease, and obstructive sleep apnea. The company plans to present additional data from the Phase 3 Launch-HTN trial at an upcoming medical conference.
Mineralys Therapeutics (NASDAQ: MLYS) ha annunciato i risultati dettagliati del suo trial pivotale di Fase 2 Advance-HTN che valuta il lorundrostat per l'ipertensione non controllata e resistente. Il trial ha dimostrato che il lorundrostat 50 mg ha raggiunto una riduzione assoluta di 15,4 mmHg e una riduzione aggiustata per placebo di 7,9 mmHg (p=0,001) della pressione sanguigna alla settimana 12.
Lo studio ha mostrato un profilo di sicurezza favorevole con modeste variazioni nei livelli di potassio, sodio e eGFR. Il trial ha incluso una popolazione di pazienti diversificata, con il 40% di donne e il 53% di partecipanti neri. Eventi avversi gravi si sono verificati nel 6%, 8% e 2% dei pazienti nei gruppi lorundrostat 50 mg, 50-100 mg e placebo rispettivamente.
Il lorundrostat funziona come un inibitore altamente selettivo dell'aldosterone sintasi, mirato all'ipertensione, alla malattia renale cronica e all'apnea ostruttiva del sonno. L'azienda prevede di presentare ulteriori dati dal trial di Fase 3 Launch-HTN in un prossimo congresso medico.
Mineralys Therapeutics (NASDAQ: MLYS) anunció resultados detallados de su ensayo pivotal de Fase 2 Advance-HTN que evalúa lorundrostat para la hipertensión no controlada y resistente. El ensayo demostró que lorundrostat 50 mg logró una reducción absoluta de 15.4 mmHg y una reducción ajustada por placebo de 7.9 mmHg (p=0.001) en la presión arterial a la semana 12.
El estudio mostró un perfil de seguridad favorable con cambios modestos en los niveles de potasio, sodio y eGFR. El ensayo incluyó una población de pacientes diversa, con un 40% de mujeres y un 53% de participantes negros. Se produjeron eventos adversos graves en el 6%, 8% y 2% de los pacientes en los grupos de lorundrostat 50 mg, 50-100 mg y placebo, respectivamente.
El lorundrostat actúa como un inhibidor altamente selectivo de la aldosterona sintasa, dirigido a la hipertensión, la enfermedad renal crónica y la apnea obstructiva del sueño. La empresa planea presentar datos adicionales del ensayo de Fase 3 Launch-HTN en una próxima conferencia médica.
미네랄리스 테라퓨틱스 (NASDAQ: MLYS)는 조절되지 않거나 저항성 고혈압에 대한 로룬드로스타트의 평가를 위한 2상 주요 시험인 Advance-HTN의 상세 결과를 발표했습니다. 이 시험은 로룬드로스타트 50 mg가 12주차에 15.4 mmHg의 절대 감소와 플라시보 조정 감소 7.9 mmHg (p=0.001) 를 달성했음을 보여주었습니다.
연구는 칼륨, 나트륨 및 eGFR 수치에서 소폭의 변화를 보이며 유리한 안전성 프로파일을 나타냈습니다. 이 시험은 40%의 여성과 53%의 흑인 참가자가 포함된 다양한 환자 집단을 포함했습니다. 심각한 부작용은 각각 로룬드로스타트 50 mg, 50-100 mg 및 플라시보 그룹에서 6%, 8% 및 2%의 환자에게 발생했습니다.
로룬드로스타트는 고혈압, 만성 신장 질환 및 폐쇄성 수면 무호흡증을 겨냥한 매우 선택적인 알도스테론 합성 효소 억제제로 작용합니다. 이 회사는 다가오는 의료 회의에서 3상 Launch-HTN 시험의 추가 데이터를 발표할 계획입니다.
Mineralys Therapeutics (NASDAQ: MLYS) a annoncé des résultats détaillés de son essai pivot de phase 2 Advance-HTN évaluant le lorundrostat pour l'hypertension incontrôlée et résistante. L'essai a démontré que le lorundrostat 50 mg a atteint une réduction absolue de 15,4 mmHg et une réduction ajustée par placebo de 7,9 mmHg (p=0,001) de la pression artérielle à la semaine 12.
Cette étude a montré un profil de sécurité favorable avec des changements modestes des niveaux de potassium, de sodium et de l'eGFR. L'essai a inclus une population de patients diversifiée, avec 40 % de femmes et 53 % de participants noirs. Des événements indésirables graves se sont produits chez 6 %, 8 % et 2 % des patients dans les groupes lorundrostat 50 mg, 50-100 mg et placebo respectivement.
Le lorundrostat fonctionne comme un inhibiteur d'aldostérone synthase hautement sélectif, ciblant l'hypertension, la maladie rénale chronique et l'apnée du sommeil obstructive. La société prévoit de présenter des données supplémentaires de l'essai de phase 3 Launch-HTN lors d'une prochaine conférence médicale.
Mineralys Therapeutics (NASDAQ: MLYS) hat detaillierte Ergebnisse seiner Phase-2-Studie Advance-HTN veröffentlicht, die lorundrostat bei unkontrollierter und resistenter Hypertonie bewertet. Die Studie zeigte, dass lorundrostat 50 mg eine absolute Reduktion von 15,4 mmHg und eine placebo-adjustierte Reduktion von 7,9 mmHg (p=0,001) des Blutdrucks in der Woche 12 erreichte.
Die Studie wies ein günstiges Sicherheitsprofil mit moderaten Veränderungen der Kalium-, Natrium- und eGFR-Werte auf. Die Studie umfasste eine vielfältige Patientengruppe, darunter 40% Frauen und 53% schwarze Teilnehmer. Schwere unerwünschte Ereignisse traten bei 6%, 8% und 2% der Patienten in den lorundrostat 50 mg, 50-100 mg und Placebo-Gruppen auf.
Lorundrostat wirkt als hochselektiver Aldosteronsynthase-Inhibitor, der auf Hypertonie, chronische Nierenerkrankungen und obstruktive Schlafapnoe abzielt. Das Unternehmen plant, weitere Daten aus der Phase-3-Studie Launch-HTN auf einer bevorstehenden medizinischen Konferenz zu präsentieren.
- Significant blood pressure reduction achieved (15.4 mmHg absolute, 7.9 mmHg placebo-adjusted)
- Favorable safety profile with low discontinuation rates
- Strong trial diversity with 40% women and 53% Black participants
- Successful completion of both pivotal trials (Advance-HTN and Launch-HTN)
- Higher incidence of serious adverse events in treatment groups (6-8%) vs placebo (2%)
- Hyperkalemia observed in 2.1-3.2% of patients after validation
Insights
Mineralys Therapeutics has delivered statistically significant results from their Advance-HTN pivotal trial, demonstrating that lorundrostat 50 mg achieved a robust
The trial's design merits particular attention - using 24-hour ambulatory blood pressure monitoring rather than office measurements provides substantially more reliable data. The patient population is also noteworthy, with
Safety data appears manageable. Expected electrolyte changes occurred (confirmed hyperkalemia rates of
Lorundrostat's mechanism - inhibiting aldosterone synthase rather than blocking receptors - potentially differentiates it from existing mineralocorticoid receptor antagonists like spironolactone, which often cause troublesome side effects limiting their use.
With both pivotal trials now reporting positive outcomes, lorundrostat appears well-positioned in the development pathway, representing a potential advance for patients whose hypertension remains uncontrolled despite optimal standard therapy.
These Advance-HTN results represent a significant milestone for Mineralys, demonstrating lorundrostat's efficacy in the challenging resistant hypertension population. The 15.4 mmHg absolute reduction is substantial for patients who remain uncontrolled despite multiple medications.
The trial's inclusion of
Lorundrostat's aldosterone synthase inhibition mechanism targets a distinct pathway in blood pressure regulation compared to standard therapies. This approach could position it as complementary to existing options rather than directly competitive, potentially expanding treatment possibilities for specialists managing complex cases.
The safety profile reveals the expected class effects on electrolytes but at manageable levels, with confirmed hyperkalemia rates remaining in the low single digits. This compares favorably to the mineralocorticoid receptor antagonists currently available, where hyperkalemia often limits clinical utility.
With two successful pivotal trials now completed, Mineralys appears positioned to advance toward regulatory submissions. For a company with
– Lorundrostat 50 mg dose achieved a 15.4 mmHg absolute reduction and 7.9 mmHg placebo-adjusted reduction (p=0.001), assessed by 24hr ABPM at week 12, with favorable safety and tolerability profile –
– Lorundrostat is a highly selective aldosterone synthase inhibitor that disrupts aldosterone biosynthesis rather than blocking the mineralocorticoid receptor –
– Data from Advance-HTN support the potential of lorundrostat as a best-in-class treatment for high-risk patients with uncontrolled or resistant hypertension who would normally be treated in a specialist setting –
RADNOR, Pa., March 29, 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 detailed results from the Phase 2 Advance-HTN trial, one of two pivotal trials evaluating lorundrostat in patients with confirmed uncontrolled hypertension (uHTN) or resistant hypertension (rHTN). In the trial, lorundrostat 50 mg demonstrated a 15.4 mmHg absolute reduction and a 7.9 mmHg placebo-adjusted reduction at week 12. Additionally, lorundrostat demonstrated a favorable safety and tolerability profile, with modest changes in potassium, sodium and eGFR, and a low discontinuation rate.
“With the recent announcement of data from our two pivotal trials, we now have a comprehensive dataset demonstrating the robust and consistent blood pressure reductions of lorundrostat in two distinct but complementary patient populations—real-world setting in Launch-HTN, and those with optimally treated yet uncontrolled hypertension in the specialist setting in Advance-HTN,” stated Jon Congleton, Chief Executive Officer of Mineralys Therapeutics. “These findings underscore lorundrostat’s clinical utility across diverse care settings and also provide critical insights for both primary care providers, who manage the vast majority of hypertension patients, and specialists, who treat the most complex cases. We are excited about the potential impact lorundrostat could have as a novel treatment to address a significant unmet need in hypertension care.”
“Twenty-four-hour ambulatory blood pressure monitoring is the gold standard for assessing the true impact of an antihypertensive therapy, as it provides a more comprehensive picture of blood pressure control beyond the office setting, including overnight readings,” stated Luke Laffin, M.D., co-director of the Center for Blood Pressure Disorders in the Heart, Vascular & Thoracic Institute at Cleveland Clinic and the study’s lead author. “Along with rigorous evaluations in the Advance-HTN trial, the double-digit drop in blood pressure readings observed with lorundrostat in this trial are particularly notable given the complex characteristics of the patient population, which included a high proportion of individuals who have been historically underrepresented in hypertension clinical trials and who face a disproportionate burden of treatment-resistant hypertension.”
Following the recently announced positive topline data from both Advance-HTN and Launch-HTN pivotal trials, detailed results from Advance-HTN were presented in a late-breaking session at the American College of Cardiology’s Annual Scientific Session & Expo (ACC.25) on Saturday, March 29, 2025, at 1:30 p.m. CT.
Efficacy Results
The Advance-HTN trial was a randomized, double-blind, placebo-controlled Phase 2 pivotal trial that evaluated the efficacy and safety of lorundrostat for the treatment of confirmed uncontrolled or resistant hypertension, when used as add-on therapy to an optimized background treatment of two or three antihypertensive medications in adult subjects. The trial was designed to evaluate lorundrostat in an uncontrolled or resistant hypertensive population at the highest risk and which would normally be treated by a specialist given severity of their condition.
| Primary Endpoint | 50 mg (n=94) | 50 to 100mg (n=94) |
| Change in 24-Hour Average SBP at Week 12 | -7.9 mmHg placebo-adjusted change (p=0.001) | -6.5 mmHg placebo-adjusted change (p=0.006) |
| Key Secondary Endpoints | 50 mg (n=188, at Week 4) | |
| Change in 24-Hour Average SBP at Week 4 | -11.5 mmHg absolute change, -5.3 mmHg placebo-adjusted change (p<0.001) | |
| Proportion with 24-Hour Average SBP < 125 mmHg at Week 4 | (p<0.001) | |
| Change in 24-Hour Average SBP at Week 4 in Patients on 2 Background Medications | -11.2 mmHg absolute change, -6.1 mmHg placebo-adjusted change (p=0.001) | |
| Change in 24-Hour Average SBP at Week 4 in Patients on 3 Background Medications | -11.8 mmHg absolute change, -4.6 mmHg placebo-adjusted change (p=0.060) | |
Safety and Tolerability Results
Lorundrostat demonstrated a favorable safety and tolerability profile in the Advance-HTN trial, with modest changes in potassium, sodium and eGFR, and a low discontinuation rate. The anticipated on-target effects on serum electrolytes, increased serum potassium and reduced serum sodium were modest and rapidly reversible upon discontinuation of lorundrostat. Suppression of cortisol production was not observed and there was a very low incidence of drug-related serious adverse events (SAEs) resulting in discontinuation or dose-adjustment of study medication.
- SAEs occurred in
6% ,8% and2% of patients in the lorundrostat 50 mg, lorundrostat 50 to 100 mg and placebo arms, respectively. - Treatment-related SAEs occurred in
2% ,1% and0% of patients in the lorundrostat 50 mg, lorundrostat 50 to 100 mg and placebo arms, respectively. - The incidence of hyperkalemia (serum potassium >6.0 mmol/L) at the scheduled study visit was
5.3% and7.4% in the 50 mg and 50 to 100 mg arms, respectively. The per-protocol procedure for validation of suspected factitious hyperkalemia specified a repeat potassium measurement within 72 hours while still taking study medication to ascertain the true incidence of hyperkalemia. After exclusion of the spurious results, the values for confirmed hyperkalemia were2.1% and3.2% , respectively.
"The safety findings from the Advance-HTN trial further reinforce lorundrostat’s favorable benefit-risk profile, even in a high-risk population that would normally be treated by specialists rather than general practitioners. The study enrolled patients with confirmed uncontrolled or resistant hypertension—
Mineralys plans to provide additional data from the pivotal Phase 3 Launch-HTN at an upcoming medical conference and in a peer-reviewed publication. Additionally, the ongoing Transform-HTN open-label extension trial allows subjects to continue to receive lorundrostat and obtain additional safety and efficacy data.
Conference Call
The Company’s management team will host a conference call on Tuesday, April 1, 2025, at 8:00 a.m. ET. To access the call, please dial 1-877-704-4453 in the U.S. or 1-201-389-0920 outside the U.S. A live webcast of the conference call may be found here. A replay of the call will be available on the “News & Events” page in the Investor Relations section of the Mineralys Therapeutics website (click here).
About Hypertension
Having sustained, elevated blood pressure (or hypertension) increases the risk of heart disease, heart attack and stroke, which are leading causes of death in the U.S. In 2020, more than 670,000 deaths in the U.S. included hypertension as a primary or contributing cause. Hypertension and related health issues resulted in an average annual economic burden of about
Less than
About Lorundrostat
Lorundrostat is a proprietary, orally administered, highly selective aldosterone synthase inhibitor being developed for the treatment of uncontrolled or resistant hypertension, 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 approximately a
In a Phase 2, proof-of-concept trial (Target-HTN) in uncontrolled or resistant hypertensive subjects, once-daily lorundrostat demonstrated statistically significant and clinically meaningful blood pressure reduction in both automated office blood pressure measurement and 24-hour ambulatory blood pressure monitoring. Adverse events observed were a modest increase in serum potassium, decrease in estimated glomerular filtration rate, urinary tract infection and hypertension with one serious adverse event possibly related to study drug being hyponatremia.
About Advance-HTN
The Advance-HTN trial (NCT05769608) was a randomized, double-blind, placebo-controlled Phase 2 clinical trial that evaluated the efficacy and safety of lorundrostat for the treatment of uncontrolled or resistant hypertension, when used as an add-on therapy to a standardized background treatment of two or three antihypertensive medications in adult subjects. Subjects who meet screening criteria had their existing hypertension medications discontinued and start on a standard regimen of an angiotensin II receptor blocker (ARB) and a diuretic, if previously on two medications, or a standard regimen of ARB, diuretic and calcium channel blocker if previously on three to five medications. Subjects who remained hypertensive despite the standardized regimen were then randomized into three cohorts and treated for twelve weeks: lorundrostat 50 mg once-daily (QD), lorundrostat 50 mg QD and an option to titrate to 100 mg QD at week four based on defined criteria, or placebo. The trial’s primary endpoint was the change in 24-hour ambulatory systolic blood pressure at week twelve from baseline for active cohorts versus placebo.
About Mineralys
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 https://mineralystx.com. Follow Mineralys on LinkedIn and Twitter.
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 Advance-HTN and Launch-HTN may serve as pivotal trials in any submission of a new drug application (NDA) to the United States Food and Drug Administration (FDA); the Company’s ability to evaluate lorundrostat as a potential treatment for CKD, OSA, uHTN or rHTN; and the planned future clinical development of lorundrostat and the timing thereof. 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; 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.
Contact:
Investor Relations
investorrelations@mineralystx.com
Media Relations
Tom Weible
Elixir Health Public Relations
Phone: (1) 515-707-9678
Email: tweible@elixirhealthpr.com
FAQ
What were the key efficacy results of MLYS's lorundrostat in the Advance-HTN trial?
What safety concerns were reported for MLYS's lorundrostat in the March 2025 trial?
How does MLYS's lorundrostat work differently from other hypertension treatments?
What was the demographic composition of MLYS's Advance-HTN trial?
