A Phase 2, Multicenter, Randomized, Double Blind, Placebo Controlled, Crossover Study to Evaluate the Efficacy and Safety of Lorundrostat in Participants With Moderate to Severe Obstructive Sleep Apnea and Hypertension

The primary purpose of the study is to assess the effect of lorundrostat taken orally (po) once a day on the Apnea-Hypopnea Index (AHI) in participants with moderate to severe obstructive sleep apnea (OSA) and hypertension.

Start Date01 Mar 2025

Sponsor / Collaborator

Mineralys Therapeutics, Inc.

NCT06150924

/ Active, not recruitingPhase 2

A Randomized, Crossover, Double Blind, Placebo Controlled, Phase 2 Study to Evaluate the Efficacy and Safety of Lorundrostat in Addition to Sodium-Glucose Cotransporter-2 Inhibitors, in Adults with Hypertension and Chronic Kidney Disease with Albuminuria

This is a randomized, double-blind (DB), placebo controlled, crossover study with a two-period, two-sequence (2x2) design evaluating the efficacy and safety of 25 mg QD lorundrostat (an aldosterone synthase inhibitor [ASI]) in addition to a SGLT2i for the treatment of hypertension in subjects with CKD and albuminuria while receiving stable treatment with an Angiotensin-converting enzyme inhibitor (ACEi) or an Angiotensin receptor blocker (ARB). Subjects will be at least 18 years old with hypertension, and mild to severe CKD with albuminuria at the Screening Visit.

Start Date14 Dec 2023

Sponsor / Collaborator

Mineralys Therapeutics, Inc.

NCT06153693

/ CompletedPhase 3

A Randomized, Double-Blind, Placebo Controlled, Parallel Arm, Multicenter Phase 3 Study to Evaluate the Efficacy and Safety of Lorundrostat in Subjects With Uncontrolled and Resistant Hypertension

This is a Phase 3 trial to evaluate the BP-lowering effect of lorundrostat (an aldosterone synthase inhibitor) in subjects with uncontrolled and resistant hypertension taking between 2 and 5 anti-hypertensive (AHT) medications.

Start Date22 Nov 2023

Sponsor / Collaborator

Mineralys Therapeutics, Inc.

100 Clinical Results associated with Lorundrostat

100 Translational Medicine associated with Lorundrostat

100 Patents (Medical) associated with Lorundrostat

Literatures (Medical) associated with Lorundrostat

01 Aug 2024·Clinical and Translational Science

First‐in‐human study evaluating safety, pharmacokinetics, and pharmacodynamics of lorundrostat, a novel and highly selective aldosterone synthase inhibitor

Article

Author: Ohta, Yoshiyasu ; Shimizu, Hidetoshi ; van Lier, Jan Jaap ; Fujii, Aya ; Djedjos, Stephen ; Slingsby, B. T. ; Rahman, Sheikh Mohammed Ashfaq ; Kawai, Mizue ; Sugimoto‐Kawabata, Kanami ; Rodman, David M. ; van Iersel, Mattheus (Thijs) ; Hiraga, Yuki ; Ogawa, Kei ; Tortorici, Michael A.

AbstractDysregulation of the mineralocorticoid hormone aldosterone is an increasingly prevalent cause of hypertension. Aldosterone synthase (CYP11B2) shares 93% homology to 11β‐hydroxylase (CYP11B1), which produces cortisol. Lorundrostat, a highly selective inhibitor of CYP11B2, is a potential safe and effective treatment for aldosterone‐dependent, uncontrolled hypertension, including treatment‐resistant hypertension. Lorundrostat showed highly selective inhibition of CYP11B2 in vitro, with 374‐fold selectivity for CYP11B2 vs. CYP11B1. A first‐in‐human study of single ascending doses ranging from 5 to 800 mg and multiple ascending doses ranging from 40 to 360 mg once daily was conducted in healthy participants. After single‐ and multiple‐dose administration, lorundrostat plasma levels peaked 1–3 h after administration with a t1/2 of 10–12 h. Plasma aldosterone decreased up to 40% with single 100‐mg to 200‐mg doses and up to 70% with single 400 to 800‐mg doses. Plasma aldosterone returned to baseline within 16 h after single 100‐mg doses and multiple once‐daily 120‐mg doses. Lorundrostat demonstrated a favorable safety profile in healthy participants. Dose‐ and exposure‐dependent inhibition of renal tubular sodium reabsorption was observed across a clinically relevant dose range with no suppression of basal or cosyntropin‐stimulated cortisol production and only a modest increase in mean serum potassium.

07 Jan 2024·European Heart Journal

More on aldosterone biosynthesis inhibition and resistant hypertension: a Phase-2 study with lorundrostat

Article

Author: Galiuto, Leonarda ; Volpe, Massimo

01 Jan 2024·Current Problems in Cardiology

Hypertension and Lorundrostat: Key Discoveries From the TARGET-HTN Trial

Review

Author: Nawani, Komal Devi ; Ahmed, Aliza ; Irfan, Hamza

Hypertension, characterized by persistent high blood pressure levels, is a major global health concern, contributing significantly to the risk of cardiovascular diseases (CVD) and overall mortality. It is classified into primary and secondary hypertension, with its prevalence steadily increasing due to ageing populations and unhealthy lifestyle factors. The World Health Organization (WHO) reports a staggering rise in hypertension cases, affecting one in 3 adults worldwide, doubling from 1990 to 2019. A significant development in the field of hypertension treatment is the Target-HTN trial, which investigated the efficacy of lorundrostat, an aldosterone synthase inhibitor, in reducing systolic blood pressure. This trial involved 2 cohorts. Cohort 1, comprising patients with suppressed plasma renin activity and elevated serum aldosterone levels, showed promising results. Lorundrostat doses of 100 mg and 50 mg administered once daily led to substantial reductions in systolic blood pressure compared to a placebo group. Cohort 2, although considered exploratory, also exhibited a notable reduction in systolic blood pressure with a 100 mg once-daily dose of lorundrostat. In conclusion, the Target-HTN trial has demonstrated that lorundrostat, an aldosterone synthase inhibitor, holds promise as an innovative therapeutic approach for reducing systolic blood pressure, especially in hypertensive patients with suppressed plasma renin activity and elevated serum aldosterone levels. These findings advocate for the initiation of Phase 3 trials to further validate the safety and efficacy of lorundrostat in a larger and more diverse patient population.

News (Medical) associated with Lorundrostat

12 Mar 2025

·www.globenewswire.com

Mineralys Therapeutics Announces Pricing of $175.0 Million Underwritten Public Offering of Common Stock

RADNOR, Pa., March 11, 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, announced today the pricing of an underwritten public offering of 12,962,962 shares of its common stock at a public offering price of $13.50 per share. The aggregate gross proceeds to Mineralys from the offering, before deducting underwriting discounts and commissions and other estimated offering expenses, are expected to be approximately $175.0 million. In addition, Mineralys has granted the underwriters a 30-day option to purchase up to an additional 1,944,444 shares of its common stock. All of the securities to be sold in the offering are to be sold by Mineralys. The offering is expected to close on or about March 13, 2025, subject to the satisfaction of customary closing conditions. BofA Securities, Evercore ISI, Goldman Sachs & Co. LLC, Stifel and Wells Fargo Securities are acting as joint book-running managers for the offering. LifeSci Capital is acting as lead manager and H.C. Wainwright & Co. is acting as co-manager for the offering. Mineralys intends to use the net proceeds from the proposed offering to fund clinical development of lorundrostat, including research and development and manufacturing, and pre-commercialization activities, as well as for working capital and general corporate purposes. The securities described above are being offered by Mineralys pursuant to a shelf registration statement previously filed and declared effective by the Securities and Exchange Commission (SEC). A preliminary prospectus supplement and accompanying prospectus relating to the offering has been filed, and a final prospectus supplement and accompanying prospectus related to the offering will be filed with the SEC. When available, copies of the final prospectus supplement and the accompanying prospectus relating to the offering may be obtained from: BofA Securities NC1-022-02-25, Attention: Prospectus Department, 201 North Tryon Street, Charlotte, North Carolina 28255-0001 or by email at dg.prospectus_requests@bofa.com; Evercore Group L.L.C., Attention: Equity Capital Markets, 55 East 52nd Street, 36th Floor, New York, New York 10055, by telephone at (888) 474-0200, or by email at ecm.prospectus@evercore.com; Goldman Sachs & Co. LLC, Attention: Prospectus Department, 200 West Street, New York, NY 10282, via telephone: (866) 471-2526, via fax: 212-902-9316, or via email: prospectus-ny@ny.email.gs.com; Stifel, Nicolaus & Company, Incorporated, Attention: Syndicate, One Montgomery Street, Suite 3700, San Francisco, California 94104, via telephone at (415) 364-2720 or via email at syndprospectus@stifel.com; or Wells Fargo Securities, LLC, Attention: WFS Customer Service, 608 2nd Avenue South, Suite 1000, Minneapolis, MN 55402, by telephone at 1-800-645-3751, or by email at wfscustomerservice@wellsfargo.com. Electronic copies of the preliminary prospectus supplement and accompanying prospectus will also be available on the website of the SEC at http://www.sec.gov. This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such jurisdiction. About MineralysMineralys 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 cardiorenal conditions affected by dysregulated aldosterone, including hypertension, CKD and OSA. Mineralys is based in Radnor, Pennsylvania, and was founded by Catalys Pacific. Forward-Looking StatementsStatements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements regarding, among other things, the completion of the proposed public offering and the anticipated use of proceeds therefrom. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. These forward-looking statements are based upon Mineralys’ current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks and uncertainties associated with market conditions, the satisfaction of customary closing conditions related to the proposed public offering, and the other risks described in Mineralys’ filings with the SEC. All forward-looking statements contained in this press release speak only as of the date on which they were made. Mineralys undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law. CONTACTS Investor Relationsinvestorrelations@mineralystx.com Media RelationsTom WeibleElixir Health Public RelationsPhone: (1) 515-707-9678Email: tweible@elixirhealthpr.com

Clinical Study

10 Mar 2025

·www.fiercebiotech.com

Mineralys’ stock jumps as hypertension drug posts double clinical wins

“We believe the clinical profile observed for lorundrostat supports the potential regulatory approval of this novel agent and its significant commercial value,” Mineralys\' CEO said.\n Mineralys Therapeutics enjoyed a big stock bump after its aldosterone synthase inhibitor chalked up wins in two types of hypertension.The therapy, called lorundrostat, hit the primary endpoint of the phase 3 Launch-HTN trial of 1,083 adults with uncontrolled hypertension (uHTN) or resistant hypertension (rHTN) by demonstrating a statistically significant mean reduction from baseline in placebo-adjusted systolic blood pressure at week six.Specifically, patients receiving 50 mg lorundrostat saw a 16.9 mmHg in their blood pressure, which equated to a placebo-adjusted reduction of 9.1 mmHg. This benefit continued into week 12, which demonstrated a placebo-adjusted reduction of 11.7 mmHg, Mineralys said in a March. 10 release.The change in blood pressure was similar regardless of whether the patients had uHTN, meaning they were using two background antihypertensives, or had rHTN, meaning they were on between three and five hypertensives, the biotech noted.In the same release, Mineralys revealed that a phase 2 Advance-HTN trial of lorundrostat in uHTN or rHTN when used as add-on therapy to an optimized background treatment of two or three antihypertensive medications also hit its endpoint. Specifically, 50 mg lorundrostat was linked to a placebo-adjusted reduction in blood pressure of 7.9 mmHg at week 12.Only one patient in the 50 mg cohort of Launch-HTN experienced a treatment-related serious adverse event, and Mineralys said the results from both trials support a favorable benefit-risk profile for lorundrostat. The incidence of hyperkalemia—defined as serum potassium above 6.0 mmol/L—in the 50 mg arms and the dose escalation arms, was 1.1% and 1.5%, respectively, in Launch-HTN trial and 5.3% and 7.4% in Advance-HTN.“The positive results and clinically meaningful reduction in blood pressure observed in the Launch-HTN and Advance-HTN trials show us that lorundrostat has the potential to be a transformative new therapy for the approximately 15 to 20 million patients with uncontrolled hypertension in the United States,” Mineralys CEO Jon Congleton said in the release.“We have now completed three successful clinical trials demonstrating the efficacy, safety and tolerability of lorundrostat and the importance of targeting dysregulated aldosterone,” Congleton added. “We believe the clinical profile observed for lorundrostat supports the potential regulatory approval of this novel agent and its significant commercial value.”Investors appeared equally impressed, sending Mineralys’ stock was up initially 45% to $15.20 in pre-market trading Monday from a Friday closing price of $10.52. The biotech went public via a $192 million IPO and a debut share price of $16.This morning’s results are a further endorsement of the theory that inhibiting the aldosterone synthase enzyme can lower levels of a blood pressure hormone. Mineralys isn’t the only company to have followed this path, with AstraZeneca having entered the space through its $1.8 billion takeover of CinCor Pharma in 2023.

Clinical ResultPhase 3Phase 2AcquisitionIPO

10 Mar 2025

·endpts.com

Mineralys’ Phase 3 blood pressure pill data support potential FDA approval

Topline pivotal data suggest that Mineralys Therapeutics’ experimental hypertension pill is a good prospect not only for approval but also for widespread adoption as a treatment for patients whose condition has not responded to other drugs. The company’s stock $MLYS rose 52% in early trading. The Phase 3 Launch-HTN trial signed up over 1,000 adults whose high blood pressure was uncontrolled despite taking two to five background antihypertensive medications. Two doses of Mineralys’ lorundrostat were tested: One group received the aldosterone synthase inhibitor at 50 mg once daily, and another group at a 50 mg-daily dose titrated up to 100 mg per day, as needed, at week six. After six weeks, pooled data from patients in both lorundrostat arms showed a blood pressure reduction of 9.1 mmHg more than those with a placebo (p<0.0001), the company said Monday. After a further six weeks, the placebo-adjusted blood pressure drop in the 50 mg-only group had deepened to 11.7 mmHg, which was also significant. However, patients who had their doses titrated up to 100 mg per day had a lesser blood pressure reduction at the 12-week point — just 8.4 mmHg on a placebo-adjusted basis (p<0.0016). Mineralys also said that “equivalent” systolic blood pressure cuts were seen in subjects with uncontrolled hypertension, who were on two antihypertensive medications, and in those with resistant hypertension, who were taking three to five drugs. Treatment emergent serious adverse events (SAEs) were seen in 2.2% of patients in the 50 mg and 0.7% in the 50 mg with optional escalation to 100 mg arms, respectively, Mineralys said, versus 3% with placebo. One subject in the 50 mg arm had an SAE that was related to lorundrostat. The 9.1 mmHg benefit over placebo on the primary endpoint meets Stifel analysts’ “upside” case. In a Feb. 24 note, the analysts wrote that a benefit of between 8 and 10 mmHg would not only be approvable, but should secure broad insurance coverage for lorundrostat as a fourth-line hypertension therapy. Lorundrostat appears to be a better prospect than the last drug approved for resistant hypertension. Idorsia’s endothelin receptor antagonist Tryvio reached the US a year ago on the strength of a 3.8 mmHg reduction. But this was seen with the lower dose in its pivotal trial; the higher dose was not approved because of safety concerns. Tryvio’s label carries a black box warning of embryo-fetal toxicity. Idorsia’s efforts to sign up a partner for Tryvio fell through last month, leaving the company in a difficult financial position. Mineralys also released data from a Phase 2 study called Advance-HTN in patients taking an optimized background treatment of two or three antihypertensive drugs. This study also hit its primary endpoint, yielding a placebo-adjusted reduction in systolic BP of 7.9 mmHg at three months with a 50 mg dose of lorundrostat. Blood pressure was measured slightly differently here, using a 24-hour average, whereas Phase 3 patients’ blood pressure was measured in their doctors’ offices. Office blood pressure measurements tend to be slightly higher than ambulatory measurements because of the so-called white coat syndrome . The company said that efficacy in the dose-escalation cohort and safety and tolerability data “mirrored the pattern” seen in Launch-HTN. Further data from Advance-HTN will be presented on March 29 at the American College of Cardiology’s annual meeting. Editor’s note: This article has been updated with Mineralys’ the latest stock move.

Clinical ResultPhase 3Phase 2

100 Deals associated with Lorundrostat

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Resistant hypertension	Phase 3	United States	Mineralys Therapeutics, Inc.	22 Nov 2023
Resistant hypertension	Phase 3	Spain	Mineralys Therapeutics, Inc.	22 Nov 2023
Resistant hypertension	Phase 3	Romania	Mineralys Therapeutics, Inc.	22 Nov 2023
Resistant hypertension	Phase 3	Netherlands	Mineralys Therapeutics, Inc.	22 Nov 2023
Resistant hypertension	Phase 3	Australia	Mineralys Therapeutics, Inc.	22 Nov 2023
Resistant hypertension	Phase 3	Italy	Mineralys Therapeutics, Inc.	22 Nov 2023
Resistant hypertension	Phase 3	Canada	Mineralys Therapeutics, Inc.	22 Nov 2023
Resistant hypertension	Phase 3	Bulgaria	Mineralys Therapeutics, Inc.	22 Nov 2023
Resistant hypertension	Phase 3	Puerto Rico	Mineralys Therapeutics, Inc.	22 Nov 2023
Resistant hypertension	Phase 3	Germany	Mineralys Therapeutics, Inc.	22 Nov 2023

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05769608 (ADVANCE-HTN, Company_Website) Manual	Phase 2	Resistant hypertension	-	Lorundrostat 50 mg	(bxzjzksjmz) = qswgfuhqic hkutlbauto (dwrvtvrcld ) Met View more	Positive	10 Mar 2025
				Lorundrostat 50-100 mg	(zgmmnptwgc) = odwigeiyni rumtwtwnnl (qpjqhvbugv )
NCT06153693 (Launch-HTN, Company_Website) Manual	Phase 3	Resistant hypertension	1,083	Lorundrostat 50 mg	(hcewovlmdi) = uqzevwmzuk cbvzikgwyj (ommyjjszcg ) Met View more	Positive	10 Mar 2025
				Lorundrostat 50-100 mg	(iosfofpxze) = amfayfvind xmbdbhkqss (hnfcjtorou ) View more
NCT05001945 (Target-HTN, CTgov)	Phase 2	Hypertension, Renal	200	Placebo (Placebo - Part 1)	bjmfmlbkzi(hviixtwgxp) = zzcxmngsip xxmozhdrbe (dlmibperac, fuejhowomy - jcvxlsbnun) View more	-	05 Jan 2024
				Lorundrostat (Lorundrostat 12.5 mg BID - Part 1)	bjmfmlbkzi(hviixtwgxp) = imlgxyuhwm xxmozhdrbe (dlmibperac, wnfgjbcrsb - xdmckkuarq) View more
NCT05001945 (Target-HTN, GlobeNewswire) Manual	Phase 2	Hypertension	200	lorundrostat	(kdbzunfuka) = ksmswxnkhw qkjivhdtwh (nzwweqwtxf )	Positive	11 Nov 2023
				lorundrostat (50mg)	(brttpxmdmt) = yfxbcjzofb xcpdnfkhqi (uzefaaypqy )
NCT05001945 (Target-HTN, Pubmed) Manual	Phase 2	Hypertension	200	lorundrostat 12.5 mg	(kqoutczasr) = xwpqymxcdh bdvzmehhxy (qxhroguhes )	Positive	10 Sep 2023
				lorundrostat 25 mg	(kqoutczasr) = drkxrwsftq bdvzmehhxy (qxhroguhes )

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