Rivus制药公司宣布在《JAMA心脏病学》上发表HU6在肥胖相关心力衰竭患者中的2a期HuMAIN试验结果-动脉网

Rivus Pharmaceuticals Announces Publication of Phase 2a HuMAIN Trial of HU6 in Patients with Obesity-Related Heart Failure in JAMA Cardiology

CISION 等信源发布 2025-03-12 23:45



可切换为仅中文







–Treatment with HU6 led to significant reductions in body fat and abdominal visceral fat while preserving skeletal muscle in patients with obesity-related heart failure with preserved ejection fraction (HFpEF) –

–使用HU6治疗可显著减少伴有保留射血分数（HFpEF）的肥胖相关心力衰竭患者的体脂和腹部内脏脂肪，同时保留骨骼肌–

– HU6, a novel, once-daily, oral therapy in Phase 2 clinical development, is a Controlled Metabolic Accelerator, a new class of investigational therapies designed to selectively reduce body fat while maintaining muscle mass –

– HU6，一种新型的、每日一次的口服疗法，目前处于二期临床开发阶段，是一种受控代谢加速器，属于旨在选择性减少体脂同时保持肌肉质量的全新研究性疗法类别 –

CHARLOTTESVILLE, Va.

夏洛茨维尔，弗吉尼亚州

, and

，以及

SOUTH SAN FRANCISCO, Calif.

加利福尼亚州南旧金山

，

March 12, 2025

2025年3月12日

/PRNewswire/ -- Rivus Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company dedicated to treating cardiometabolic diseases driven by obesity, today announced the publication of results of the Phase 2a HuMAIN clinical trial of HU6 in patients with obesity-related heart failure with preserved ejection fraction (HFpEF) in .

/PRNewswire/ -- Rivus Pharmaceuticals, Inc.是一家致力于治疗由肥胖引发的心脏代谢疾病的临床阶段生物制药公司，今天宣布了HU6在肥胖相关射血分数保留型心力衰竭（HFpEF）患者中的2a期HuMAIN临床试验结果的发表。

JAMA Cardiology

JAMA心脏病学

. The study met the primary endpoint of reduction in body weight with HU6 compared to placebo over the 19-week period. This reduction was driven by decreases in fat mass and visceral fat while preserving lean mass, highlighting improved body composition with HU6. Overall rates of serious adverse events (AEs) and treatment discontinuation with HU6 were low..

研究达到了在19周内HU6相较于安慰剂减轻体重的主要终点。这种减重是由脂肪量和内脏脂肪减少而瘦体质量得以保持所驱动的，突显了HU6改善身体成分的作用。HU6的严重不良事件（AEs）总体发生率和治疗中断率较低。

HU6, a novel, once-daily, oral investigational medicine, is part of Rivus' portfolio of Controlled Metabolic Accelerators (CMAs). HU6, the company's lead program, increases metabolic rate in a controlled manner enabling sustained fat loss while preserving muscle mass, the primary engine of caloric utilization in the body.

HU6是一种新型的、每日一次的口服研究性药物，属于Rivus公司控制代谢加速剂（CMAs）产品组合的一部分。HU6作为该公司的主要项目，能够以可控的方式提高代谢率，在保持肌肉质量的同时实现持续的脂肪减少，而肌肉是身体热量消耗的主要引擎。

Excess body fat plays a key role in the underlying pathology of HFpEF, an increasingly common disorder that affects a growing population of patients for whom few effective treatments are available..

过量的体脂在HFpEF的潜在病理中起着关键作用，这是一种日益常见的疾病，影响着越来越多的患者，而针对这种疾病的有效治疗方法很少。

'I am excited to see the potential of HU6 in significantly reducing visceral adiposity and total body fat without affecting lean mass in patients with obesity and HFpEF,' said

“我非常期待看到HU6在显著减少肥胖和HFpEF患者的内脏脂肪和全身脂肪而不影响瘦体质量方面的潜力，”

Ambarish Pandey

阿姆巴里什·潘迪

, M.D., a cardiologist, lead-author of the publication and member of the HuMAIN study Steering Committee. 'As we know, visceral adiposity is causally implicated in the development and progression of HFpEF and having a therapy that can directly target this could be transformative in HFpEF treatment.'.

，医学博士，心脏病学家，该出版物的第一作者以及HuMAIN研究指导委员会成员。“正如我们所知，内脏脂肪在HFpEF的发展和进展中具有因果作用，拥有一种能够直接针对这一问题的疗法可能会对HFpEF的治疗产生变革性影响。”

The published HuMAIN study results showed that HU6 resulted in a significantly greater reduction in body weight (-6.8 lbs vs -0.5 lbs, p=0.0026), total fat mass (-7.4 lbs vs. -0.88 lbs with placebo, p=0.0003), percent visceral fat (-1.5% vs. -0.2% with placebo, p=0.0028) and percent reduction in body fat percentage (-4.8% vs.

HuMAIN研究结果表明，HU6组体重显著下降（-6.8磅 vs -0.5磅，p=0.0026），总体脂肪量显著减少（-7.4磅 vs 安慰剂组的-0.88磅，p=0.0003），内脏脂肪百分比下降（-1.5% vs 安慰剂组的-0.2%，p=0.0028），体脂百分比减少（-4.8% vs。

-0.45% with placebo, p=0.0002) at 19 weeks compared with baseline. Other measures of body composition showed:.

-0.45% 与安慰剂相比，p=0.0002）在第19周时相较基线。身体组成的其他指标显示：。

No significant change in lean body mass or skeletal muscle mass with HU6 vs. placebo or with HU6 at 19 weeks compared with baseline. A reduction in abdominal visceral adipose tissue with HU6 vs. placebo (-0.19 L) in patients whose body composition was assessed by MRI.

与安慰剂相比，使用HU6并未导致瘦体质量或骨骼肌质量的显著变化，并且在19周时与基线相比也无显著变化。对于通过MRI评估身体成分的患者，HU6相较于安慰剂减少了腹部内脏脂肪组织（-0.19升）。

Although this Phase 2a study was a short duration of 19 weeks, additional secondary endpoints were assessed to evaluate the impact of HU6 on a number of cardiac markers. The findings showed:

尽管这项 2a 期研究仅持续了 19 周，但评估了额外的次要终点，以评价 HU6 对多种心脏标志物的影响。研究结果显示：

Significant improvements from placebo in left ventricular systolic function (increased left ventricular ejection fraction [LVEF] of 3.76% and decreased left ventricular end-systolic volume of -5.64 ml) and right ventricular function (right ventricular systolic [RV S'] velocity of 2.10 cm/s) as assessed by echocardiography..

与安慰剂相比，左心室收缩功能（左心室射血分数 [LVEF] 增加 3.76%，左心室收缩末期容积减少 -5.64 毫升）和右心室功能（右心室收缩 [RV S'] 速度为 2.10 厘米/秒）在超声心动图评估中均有显著改善。

Significant reductions from placebo in resting systolic blood pressure (-8.7 mm Hg) and diastolic blood pressure (-4.9 mm Hg), which was observed early and persisted throughout the study.

与安慰剂相比，静息收缩压（-8.7 毫米汞柱）和舒张压（-4.9 毫米汞柱）显著降低，这种效果出现得较早并持续整个研究过程。

No significant differences in changes in cardiac safety parameters in participants who underwent a cardiac MRI or in resting heart rate or respiratory rate.

接受心脏核磁共振成像检查的参与者在心脏安全参数、静息心率或呼吸频率的变化方面没有显著差异。

No significant difference was noted in peak exercise oxygen uptake between HU6 and placebo arms.

HU6组和安慰剂组在峰值运动摄氧量方面没有显著差异。

The safety profile of HU6 was consistent with previous studies. HU6 was well tolerated in study participants, who were on average elderly, obese, had multiple comorbidities, and were taking 15 concomitant medications. Overall rates of serious AEs were low. Four patients taking HU6 and one patient taking placebo experienced a serious AE, all of which were deemed unrelated to the study drug..

HU6的安全性特征与之前的研究一致。HU6在研究参与者中耐受性良好，这些参与者平均年龄较大、肥胖、有多重合并症，并且正在服用15种伴随药物。严重不良事件（AE）的总体发生率较低。四名服用HU6的患者和一名服用安慰剂的患者经历了严重的不良事件，所有这些事件均被认为与研究药物无关。

'Although HuMAIN was a small study of short duration powered only for a reduction in body weight, the significant improvements observed in body composition and cardiac and metabolic secondary endpoints are meaningful,' said

“尽管HuMAIN是一项仅针对体重减轻的小规模短期研究，但在身体成分和心脏及代谢次要终点观察到的显著改善是有意义的，”

Jayson Dallas

杰森·达拉斯

, M.D., chief executive officer, Rivus Pharmaceuticals. 'These positive study results, especially the improvements in cardiac structure and function, suggest that HU6 could be the first disease-modifying treatment for HFpEF, a debilitating disorder associated with poor quality of life and physical limitations.'.

医学博士，Rivus制药公司首席执行官表示：“这些积极的研究结果，尤其是心脏结构和功能的改善，表明HU6可能成为首个针对HFpEF的疾病修饰治疗药物。HFpEF是一种与生活质量差和身体受限相关的衰弱性疾病。”

Data from HuMAIN study participants in the compliance population (i.e., those who complied with taking HU6 throughout the study based on a measure of a primary metabolite of HU6) are available on the

HuMAIN研究中合规人群（即，根据HU6的一种主要代谢物的测量结果，确定在研究期间一直服用HU6的参与者）的数据可在此处获得。

Rivus website

里维斯网站

。

In addition to the Phase 2a HuMAIN study, Rivus is evaluating HU6 in the randomized, double-blind, placebo-controlled, parallel-group Phase

除了第2a阶段的HuMAIN研究外，Rivus还在随机、双盲、安慰剂对照、平行组的第2b阶段评估HU6。

2 M

2 米

-ACCEL trial (ClinicalTrials.gov: NCT05979779) in patients with MASH. The company remains on track to announce topline results from M-ACCEL in the second quarter of 2025.

-ACCEL试验（ClinicalTrials.gov: NCT05979779）针对MASH患者。公司仍有望在2025年第二季度公布M-ACCEL的初步结果。

About the Phase 2a

关于第2a阶段

HuMAIN Trial

HuMAIN试验

The multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-escalation Phase 2a HuMAIN trial (

多中心、随机、双盲、安慰剂对照、平行组、剂量递增的2a期HuMAIN试验（

ClinicalTrials.gov: NCT05284617

) evaluated the efficacy and safety of oral HU6 in patients with chronic, stable obesity-related HFpEF. In the intention-to-treat (ITT) population, 66 study participants were randomized to HU6 (starting at 150 mg/day and potentially up-titrated to 450 mg/day based on safety and tolerability) or placebo.

）评估了口服HU6在慢性、稳定性肥胖相关HFpEF患者中的疗效和安全性。在意向治疗（ITT）人群中，66名研究参与者被随机分配到HU6组（起始剂量为150毫克/天，并根据安全性和耐受性可能上调至450毫克/天）或安慰剂组。

Study participants were over age 30 (average of 64.5 years; range: 38 to 87 years) with a body mass index (BMI) .

研究参与者年龄超过30岁（平均64.5岁；范围：38至87岁），身体质量指数（BMI）。

30 kg/m2 (average of 39.4 kg/m

30公斤/平方米（平均值为39.4公斤/平方米）

) and an average body weight of 110.9 kg (245 pounds). The primary efficacy endpoint was the change in body weight from baseline to Day 134 (19 weeks). The key secondary efficacy endpoint was the change in peak oxygen uptake (VO

）平均体重为110.9公斤（245磅）。主要疗效终点是从基线到第134天（19周）的体重变化。关键的次要疗效终点是峰值摄氧量（VO的变化。

). Exploratory secondary endpoints included changes in body composition, 6-minute walk distance (6MWD), Kansas City Cardiomyopathy Questionnaire (KCCQ) score, N-terminal pro b-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (Hs-CRP) and safety/tolerability. HuMAIN was conducted at 14 clinical sites in .

).探索性的次要终点包括身体成分的变化、6分钟步行距离（6MWD）、堪萨斯城心肌病问卷（KCCQ）评分、N末端前B型钠尿肽（NT-proBNP）、高敏C反应蛋白（Hs-CRP）以及安全性和耐受性。HuMAIN在14个临床站点进行。

the United States

美国

。

About Heart Failure with Preserved Ejection Fraction (HFpEF)

关于射血分数保留的心力衰竭 (HFpEF)

Heart failure with preserved ejection fraction (HFpEF) is a chronic debilitating syndrome characterized by severely reduced exercise capacity, which degrades quality of life. Obesity is a strong risk factor for HFpEF and key contributor to the increasing worldwide prevalence of this disorder, with as many as 80% of patients with HFpEF in Western countries either overweight or obese.

射血分数保留的心力衰竭（HFpEF）是一种慢性致残综合征，其特征是运动能力严重下降，从而降低生活质量。肥胖是HFpEF的一个强风险因素，也是导致该病在全球范围内患病率上升的关键原因，在西方国家，多达80%的HFpEF患者超重或肥胖。

Specifically, systemic inflammation generated by visceral fat deposits is believed to contribute significantly to the development and progression of HFpEF. Studies have shown that the five-year survival rate in .

具体来说，内脏脂肪沉积引发的系统性炎症被认为对HFpEF的发展和进展有显著影响。研究表明，五年生存率在。

the United States

美国

for people hospitalized with HFpEF was 24.3%. Weight loss approaches that involve dieting, bariatric surgery and

因HFpEF住院的患者比例为24.3%。涉及节食、减重手术等的减重方法和策略

GLP-1

agonists work by decreasing energy intake rather than by increasing energy expenditure. In addition to loss of fat, these approaches result in marked reductions in muscle mass, which can lead to impaired function in patients with HFpEF, who are typically elderly and frail and already have reduced muscle mass..

激动剂通过减少能量摄入而不是增加能量消耗来起作用。除了脂肪减少外，这些方法还会导致肌肉质量显著下降，这可能会削弱患有HFpEF的患者的功能，这些患者通常为老年人、体弱者，并且已经存在肌肉质量下降的情况。

About Controlled Metabolic Accelerators (CMAs)

关于可控代谢加速器 (CMAs)

Rivus is advancing a new class of investigational therapies called Controlled Metabolic Accelerators (CMAs) that have the potential to improve metabolic health for people with obesity and associated metabolic diseases. Rivus' CMAs are oral small molecules in development to increase resting metabolic rate, which results in increased consumption of energy, primarily from fat.

Rivus正在推进一类名为“受控代谢加速剂（CMAs）”的新型研究性疗法，这类疗法有潜力改善肥胖及相关的代谢疾病患者的代谢健康。Rivus的CMAs是正在开发中的口服小分子药物，旨在提高静息代谢率，从而增加能量消耗，主要来源于脂肪。

The loss in fat mass may address multiple cardiometabolic conditions driven by adiposity. CMAs increase metabolism in a manner that is consistent and imperceptible to the patient by leveraging the natural metabolic process of mitochondrial uncoupling. In preclinical studies, mitochondrial uncoupling was shown to account for a significant portion (20% to 50%) of daily energy expenditure.

脂肪量的减少可能解决由肥胖引起的多种心代谢状况。CMAs通过利用线粒体解偶联的自然代谢过程，以一种一致且患者无法察觉的方式提高代谢。在临床前研究中，线粒体解偶联被证明占每日能量消耗的显著部分（20%至50%）。

Caloric-restriction strategies, on the other hand, reduce energy input and result in loss of muscle mass as well as fat. Initial data in humans has demonstrated that CMAs provided fat-selective weight loss, improved insulin sensitivity, and significantly reduced oxidative stress and inflammation..

另一方面，热量限制策略减少能量摄入，导致肌肉质量和脂肪的损失。人类的初步数据表明，CMAs 提供了选择性的减脂效果，改善了胰岛素敏感性，并显著降低了氧化应激和炎症。

About HU6

关于HU6

HU6, a novel, oral, once-daily investigational therapy, is Rivus' lead CMA. It is a purposely designed investigational oral small molecule that is intended to be a foundational monotherapy for cardiac, liver, diabetes and obesity indications. HU6 has been demonstrated to promote sustained body fat loss by imperceptibly increasing resting metabolism, which results in fat burn, while preserving muscle mass.

HU6是一种新型的、每日一次的口服研究性疗法，是Rivus公司的主要CMA。它是一种经过特意设计的研究性口服小分子，旨在成为心脏、肝脏、糖尿病和肥胖症适应症的基础单药疗法。HU6已被证明可通过不显著增加静息代谢来促进持续的体脂减少，从而实现脂肪燃烧，同时保留肌肉质量。

The current clinical development of HU6 is focused on metabolic diseases with the most morbidity and greatest treatment needs: obesity-related heart failure with preserved ejection fraction (HFpEF) and metabolic dysfunction-associated steatohepatitis (MASH)/metabolic dysfunction-associated steatotic liver disease (MASLD).

HU6当前的临床开发重点是发病率最高且治疗需求最大的代谢性疾病：射血分数保留的肥胖相关心力衰竭（HFpEF）以及代谢功能障碍相关的脂肪性肝炎（MASH）/代谢功能障碍相关的脂肪肝病（MASLD）。

To date, more than 400 patients have been treated with HU6 as part of the clinical development program..

截至目前，已有400多名患者在临床开发项目中接受了HU6的治疗。

Results of a Phase 2 metabolic study in patients with a high body mass index (BMI) and MASLD showed that once-daily HU6 significantly reduced liver fat content and body weight with no loss of lean muscle mass and improved key markers of systemic inflammation and metabolism.

高体重指数（BMI）和MASLD患者中进行的2期代谢研究结果显示，每日一次的HU6显著减少了肝脏脂肪含量和体重，且没有瘦肌肉质量的损失，并改善了系统性炎症和代谢的关键指标。

HU6 was well tolerated in this trial; side effects were mainly mild or moderate in severity. Results from the Phase 2a HuMAIN study

HU6在本试验中耐受性良好；副作用主要为轻度或中度。二期a阶段HuMAIN研究的结果

(ClinicalTrials.gov: NCT05284617

) of HU6 in patients with obesity-related HFpEF showed the trial met its primary endpoint, demonstrating that treatment with HU6 resulted in statistically significant weight loss. The rationale for the use of HU6 in HFpEF and the design of the HuMAIN trial were published in the

HU6在肥胖相关HFpEF患者中的试验显示，该试验达到了其主要终点，证明使用HU6治疗可带来统计学上显著的体重减轻。HU6在HFpEF中的应用理由以及HuMAIN试验的设计已发表在

European Journal of Heart Failure

欧洲心力衰竭杂志

在

June 2024

2024年6月

。

About Rivus Pharmaceuticals

关于Rivus Pharmaceuticals

Rivus Pharmaceuticals, Inc., a leader in mitochondrial biology, is dedicated to improving metabolic health by advancing a new class of investigational therapies called Controlled Metabolic Accelerators (CMAs). Rivus' lead CMA is the investigational small molecule HU6 in clinical development to treat obesity-related heart failure with preserved ejection fraction (HFpEF), metabolic dysfunction associated steatohepatitis (MASH)/metabolic dysfunction-associated steatotic liver disease (MASLD) and Type 2 diabetes.

Rivus制药公司是线粒体生物学领域的领导者，致力于通过推进一类名为控制代谢加速剂（CMAs）的新型研究性疗法来改善代谢健康。Rivus的主要CMA是处于临床开发阶段的研究性小分子HU6，用于治疗与肥胖相关的心力衰竭伴射血分数保留（HFpEF）、代谢功能障碍相关的脂肪性肝炎（MASH）/代谢功能障碍相关的脂肪肝病（MASLD）以及2型糖尿病。

In addition to HU6, Rivus is developing a pipeline of oral small molecule CMAs. For more information, please visit .

除了HU6，Rivus还正在开发一系列口服小分子CMA。欲了解更多信息，请访问。

www.rivuspharma.com

。

Contact:

联系人：

Sheryl Seapy

雪莉·西皮

Real Chemistry

真实化学

sseapy@realchemistry.com

949-903-4750

References

参考文献

Noureddin M, Khan S, Portell F, et al. Safety and efficacy of once-daily HU6 versus placebo in people with non-alcoholic fatty liver disease and high BMI: a randomised, double-blind, placebo-controlled phase 2a trial.

Noureddin M、Khan S、Portell F 等。每日一次 HU6 与安慰剂在非酒精性脂肪肝病和高 BMI 人群中的安全性和有效性：一项随机、双盲、安慰剂对照的 2a 期试验。

Lancet Gastroenterol Hepatol

柳叶刀胃肠病学和肝病学

. 2023;8(12):1094-1105.

. 2023；8（12）：1094-1105。

Kitzman DW, Lewis GD, Pandey A, et al. A novel controlled metabolic accelerator for the treatment of obesity-related heart failure with preserved ejection fraction: Rationale and design of the Phase 2a HuMAIN trial.

Kitzman DW，Lewis GD，Pandey A，等。一种新型可控代谢加速器用于治疗射血分数保留的肥胖相关心力衰竭：2a期HuMAIN试验的理由与设计。

Eur J Heart Fail

欧洲心脏衰竭杂志

。

June 26, 2024

2024年6月26日

。

SOURCE Rivus Pharmaceuticals

来源：里维斯制药公司

WANT YOUR COMPANY'S NEWS

想要贵公司的新闻

FEATURED ON PRNEWSWIRE.COM?