– New analysis on serum leptin levels among patients in the Target-HTN Phase 2 trial adds to emerging evidence of positive feedback loop linking obesity, leptin and aldosterone –
– Excess aldosterone in patients with visceral obesity defines a unique hypertensive endotype with potential for an enhanced response to aldosterone-targeted therapy with lorundrostat –
– Early identification and intervention with lorundrostat may result in improved clinical outcomes for obese patients with uncontrolled or resistant hypertension –
RADNOR, Pa., Nov. 11, 2023 (GLOBE NEWSWIRE) -- Mineralys Therapeutics, Inc. (Nasdaq: MLYS), a clinical-stage biopharmaceutical company focused on developing medicines to target hypertension, chronic kidney disease (CKD) and other diseases driven by abnormally elevated aldosterone, today presented data from the Target-HTN Phase 2 trial that further defines an endotype-specific targeted approach for treating uncontrolled or resistant hypertension with lorundrostat, a highly selective aldosterone synthase inhibitor. The data were presented in a poster at the American Heart Association (AHA) Scientific Sessions 2023, which is being held in Philadelphia from November 11th –13th.
Data previously presented from Target-HTN showed that elevated body mass index (BMI) was predictive of an enhanced reduction in systolic blood pressure (BP) from lorundrostat treatment. The poster presented at the AHA Scientific Sessions 2023 included a new analysis of serum leptin levels among subjects in the trial, which showed that increased BMI was correlated with increased leptin circulation. This is consistent with emerging evidence of a leptin-driven, positive feedback loop between obesity, aldosterone and hypertension.1
"Through our ongoing analyses of data from the Target-HTN trial, a profile of which patients can benefit the most from lorundrostat is emerging. After examining serum leptin levels across participants, we now have evidence that this hormone, along with elevated BMI, could be a biomarker for patients who may experience a meaningful blood pressure reduction from lorundrostat treatment," stated David Rodman, M.D., Chief Medical Officer for Mineralys. "Obesity is an epidemic and is one of the strongest risk factors for developing hypertension, which results in subsequent poor outcomes if uncontrolled. Being able to identify a hypertensive endotype, and intervene early with aldosterone-targeted therapy, would change the way clinicians currently treat the condition in practice by introducing a precision approach to care."
A pre-specified analysis from Target-HTN showed that subjects with a BMI >30kg/m2 experienced placebo-adjusted reductions in systolic BP of 16.7mmHg (p=0.002) and 12.3mmHg (p=0.03) with lorundrostat 50mg and 100mg once-daily (QD) doses, respectively. Findings from the new analysis showed that the same BMI range was associated with a 75% increase in mean serum leptin (21.6 ±1.9ng/mL in subjects with a BMI ≤30kg/m2 compared to 37.8 ±2.4ng/mL in subjects with a BMI >30kg/m2; p<0.001), indicating that increased circulating leptin may be a useful biomarker to identify lorundrostat-responsive individuals.
The Target-HTN trial demonstrated that treatment with lorundrostat at doses of 50mg and 100mg QD led to a statistically and clinically significant reduction of systolic BP in uncontrolled hypertensive individuals on at least two background antihypertensive medications. Full results from the trial were published in the Journal of the American Medical Association (JAMA) and simultaneously presented during a late-breaking science session at the 2023 AHA Hypertension Scientific Sessions in September.
Target-HTN trial results support the transition to late-stage development of lorundrostat as a treatment for uncontrolled or resistant hypertension. The Company's ongoing pivotal development program for lorundrostat to treat uncontrolled or resistant hypertension is currently enrolling subjects in the pivotal Advance-HTN trial, and the second pivotal trial, Launch-HTN, trial is expected to be initiated in the second half of 2023.
The poster at AHA Scientific Sessions 2023 titled, "Lorundrostat for Treatment of Obesity-Related, Aldosterone-Dependent Hypertension - An Endotype-Specific, Targeted Approach to the Treatment of Uncontrolled Hypertension," can be accessed on the publications page of the Mineralys corporate website.
About Target-HTN
The Target-HTN (NCT05001945) Phase 2 proof-of-concept trial was a randomized, double-blind, placebo-controlled, dose-ranging, multicenter trial conducted in the U.S. The trial was designed to evaluate the safety, efficacy, tolerability and dose response of orally administered lorundrostat on BP for the treatment of uncontrolled or resistant hypertension when used as add-on therapy to stable background treatment of two or more antihypertensive agents in 200 male and female subjects 18 years of age or older. Five active doses of lorundrostat (12.5mg QD, 50mg QD, 100mg QD, 12.5mg twice daily (BID), and 25mg BID) were compared to placebo in hypertensive subjects. 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 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 $130 billion each year in the U.S., averaged over 12 years from 2003 to 2014.
Less than 50 percent of hypertension patients achieve their blood pressure goal with currently available medications. Abnormally elevated aldosterone levels are a key factor in driving hypertension in approximately 25 percent of all hypertensive patients.
About Lorundrostat
Lorundrostat is a proprietary, orally administered, highly selective aldosterone synthase inhibitor being developed for the treatment of uncontrolled hypertension and CKD. 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 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 and other diseases driven by abnormally elevated 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 abnormally elevated aldosterone, including hypertension and CKD. Mineralys is based in Radnor, Pennsylvania, and was founded by Catalys Pacific.
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 aldosterone synthase inhibitors with an SGLT2 inhibitor may provide additive clinical benefits to patients; the Company's expectation that the Advance-HTN and the planned Phase 3 clinical trial of lorundrostat 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 or uncontrolled hypertension; the planned future clinical development of lorundrostat and the timing thereof; and the expected timing of commencement and enrollment of patients 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: 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; 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; 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.
— 對Target-HTN 2期試驗患者血清瘦素水平的新分析增加了與肥胖、瘦素和醛固酮相關的正反饋迴路的新證據 —
— 內臟肥胖患者過量的醛固酮定義了一種獨特的高血壓內型,有可能增強對使用氯倫德羅司他進行醛固酮靶向治療的反應 —
— 早期識別和干預lorundrostat可以改善患有失控或耐藥性高血壓的肥胖患者的臨床預後 —
賓夕法尼亞州拉德諾,2023年11月11日(GLOBE NEWSWIRE)——一家臨床階段的生物製藥公司Mineralys Therapeutics, Inc.(納斯達克股票代碼:MLYS),專注於開發針對高血壓、慢性腎臟病(CKD)和其他由醛固酮異常升高引起的疾病的藥物,今天公佈了Target-HTN 2期試驗的數據,該試驗進一步定義了一種內型特異性靶向治療方法使用lorundrostat(一種高度選擇性的醛固酮合酶抑制劑)治療不受控制或耐藥性高血壓。這些數據是在11月11日在費城舉行的2023年美國心臟協會(AHA)科學會議的海報中公佈的第四 —13第四。
Target-HTN先前提供的數據顯示,體重指數(BMI)升高可以預示氯倫德羅司他治療可增強收縮壓(BP)的降低。在2023年AHA科學會議上展示的海報包括對試驗中受試者血清瘦素水平的新分析,該分析表明,體重指數升高與瘦素循環增加相關。這與肥胖、醛固酮和高血壓之間存在瘦素驅動的正反饋循環的新證據一致。1
“通過我們對Target-HTN試驗數據的持續分析,可以得出哪些患者可以從lorundrostat中受益最大的概況。在檢查了參與者的血清瘦素水平之後,我們現在有證據表明,這種激素加上體重指數升高,可以成爲那些可能通過洛倫德羅司特治療獲得有意義降低血壓的患者的生物標誌物。” Mineralys首席醫學官戴維·羅德曼醫學博士說。“肥胖是一種流行病,是發生高血壓的最大風險因素之一,如果得不到控制,會導致隨後的不良預後。能夠識別高血壓內型並儘早使用醛固酮靶向治療進行干預,將引入精確的護理方法,從而改變臨床醫生目前在實踐中治療該疾病的方式。”
Target-HTN的一項預先指定的分析顯示,體重指數大於30kg/m的受試者2 經安慰劑調整後,使用氯倫德羅司他50mg和每天一次(QD)的劑量分別降低了16.7mmHg(p=0.002)和12.3mmHg(p=0.03)。新分析的結果表明,在體重指數≤30kg/m的受試者中,相同的體重指數範圍與血清瘦素平均值(21.6 ±1.9ng/mL)增加75%有關2 相比之下,體重指數大於30kg/m的受試者爲37.8 ±2.4ng/mL2; p<0.001),表明循環中的瘦素增多可能是識別對lorundrostat有反應的個體的有用生物標誌物。
Target-HTN試驗表明,使用劑量爲50mg和100mg QD的lorundrostat治療可使服用至少兩種背景抗高血壓藥物的不受控制的高血壓患者的收縮壓顯著降低。該試驗的完整結果是 已出版 在 美國醫學會雜誌 (JAMA) 並同時 呈現 在9月舉行的2023年AHA高血壓科學會議的最新科學會議上。
Target-HTN 試驗結果支持將氯倫德羅司他作爲治療失控或耐藥性高血壓的治療方法過渡到後期開發。該公司正在進行的用於治療失控或耐藥性高血壓的lorundrostat關鍵開發計劃目前正在招募受試者參加關鍵的Advance-HTN試驗,第二項關鍵試驗Launch-HTN試驗預計將於2023年下半年啓動。
2023 年 AHA Scientifiencient Sessions 上標題爲 “Lorundrostat 用於治療肥胖相關醛固酮依賴性高血壓——一種內分型特異性、有針對性的治療失控高血壓的方法” 的海報可在Mineralys公司網站的出版物頁面上查閱。
關於 Target-HTN
Target-HTN(NCT05001945)2期概念驗證試驗是在美國進行的一項隨機、雙盲、安慰劑對照、劑量範圍廣、多中心試驗。該試驗旨在評估200例男性和兩種以上抗高血壓藥物作爲穩定背景治療的附加療法對血壓進行口服洛倫德羅司特治療的安全性、有效性、耐受性和劑量反應 18歲或以上的女性受試者。將五種活性劑量的氯倫德羅司他(12.5mg QD、50mg QD、100mg QD、12.5mg 每日兩次(BID)和25mg BID)與高血壓受試者的安慰劑進行了比較。觀察到的不良事件是血清鉀略有增加、估計的腎小球濾過率降低、尿路感染和高血壓,可能與研究藥物有關的一個嚴重不良事件是低鈉血癥。
關於高血壓
血壓持續升高(或高血壓)會增加患心臟病、心臟病發作和中風的風險,而心臟病、心臟病發作和中風是美國的主要死因。2020年,美國有超過670,000例死亡將高血壓列爲主要或促成原因。從2003年到2014年,高血壓和相關的健康問題導致美國每年平均約1,300億美元的經濟負擔。
只有不到50%的高血壓患者使用目前可用的藥物實現了血壓目標。在大約25%的高血壓患者中,醛固酮水平異常升高是導致高血壓的關鍵因素。
關於 Lorundrostat
Lorundrostat 是一種專有的、口服給藥、高選擇性的醛固酮合成酶抑制劑,正在開發用於治療不受控制的高血壓和慢性腎病。Lorundrostat 旨在通過抑制 CYP11B2(負責其產生的酶)來降低醛固酮水平。與抑制皮質醇合成酶相比,Lorundrostat 在醛固酮合成酶抑制方面具有374倍的選擇性 在體外, 觀察到的半衰期爲10-12小時,顯示高血壓受試者的血漿醛固酮濃度降低了約70%。
關於 Mineralys Therapeutic
Mineralys Therapeutics是一家處於臨床階段的生物製藥公司,專注於開發針對高血壓、慢性腎病和其他由醛固酮異常升高引起的疾病的藥物。其最初的候選產品lorundrostat是一種專有的、口服的、高選擇性的醛固酮合酶抑制劑,Mineralys Therapeutics正在開發用於受醛固酮異常升高影響的心腎疾病,包括高血壓和慢性腎病。Mineralys總部位於賓夕法尼亞州的拉德納,由Catalys Pacific創立。
前瞻性陳述
Mineralys Therapeutics提醒您,本新聞稿中包含的有關非歷史事實事項的陳述是前瞻性陳述。前瞻性陳述基於我們目前的信念和預期,包括但不限於有關以下內容的陳述:lorundrostat 的潛在治療益處;公司對含有 SGLT2 抑制劑的醛固酮合酶抑制劑可能爲患者提供額外的臨床益處的期望;公司預計 Advance-HTN 和計劃中的 lorundrostat 3 期臨床試驗可能在任何新藥申請中作爲關鍵試驗(NDA)致美國食品藥品監督管理局(FDA);公司評估lorundrostat作爲慢性腎病或不受控制的高血壓的潛在治療方法的能力;lorundrostat的未來計劃臨床開發及其時機;以及患者開始和入組臨床試驗的預期時間以及臨床試驗的最終結果。由於我們業務固有的風險和不確定性,實際結果可能與本新聞稿中列出的結果有所不同,包括但不限於:我們的未來表現完全取決於lorundrostat的成功;臨床試驗和非臨床研究的開始、註冊和完成可能出現延遲;FDA的後期進展可能與第二階段會議已完成的反饋不一致,包括擬議的關鍵計劃是否會支持lorundrostat的註冊是一篇評論提交保密協議後與美國食品藥品管理局發生爭議;我們在生產、研究、臨床和非臨床測試方面對第三方的依賴;lorundrostat的意外不良副作用或療效不足,可能會限制其開發、監管部門批准和/或商業化;臨床試驗和非臨床研究的不利結果;lorundrostat先前的臨床試驗和研究結果不一定能預測未來的結果;我們在任何疫情下保持業務運營不間斷的能力或者未來公共衛生問題;美國和國外的監管發展;我們依靠田邊三菱製藥的獨家許可向我們提供開發和商業化lorundrostat的知識產權;以及我們在向美國證券交易委員會(SEC)提交的文件中描述的其他風險,包括我們在10-K表年度報告中以及隨後向美國證券交易委員會提交的任何文件中在 “風險因素” 標題下描述的其他風險。提醒您不要過分依賴這些前瞻性陳述,這些陳述僅代表截至本文發佈之日,我們沒有義務更新此類陳述以反映本文發佈之日之後發生的事件或存在的情況。本警示聲明根據1995年《私人證券訴訟改革法》的安全港條款對所有前瞻性陳述進行了全面限定。