– Study evaluating HU6 in patients with
obesity-related heart failure with preserved ejection fraction is
on track to report topline data in the second half of 2024 –
– HU6, a novel Controlled Metabolic Accelerator,
is a new class of investigational medicines designed to reduce
weight while preserving muscle –
CHARLOTTESVILLE, Va. and SAN FRANCISCO, June 26,
2024 /PRNewswire/ -- Rivus Pharmaceuticals Inc., a
clinical-stage biopharmaceutical company dedicated to improving
metabolic health, today announced publication of the rationale and
design of the company's Phase 2a HuMAIN trial in the European
Journal of Heart Failure. Rivus has completed patient enrollment in
this clinical trial of HU6, an investigational Controlled Metabolic
Accelerator (CMA), in patients with obesity-related heart failure
with preserved ejection fraction (HFpEF) and expects to report
topline data in the second half of 2024.
"HuMAIN is the first clinical trial to evaluate the effects of a
CMA in patients with obesity-related HFpEF, who have a median
survival rate of around two years following hospitalization," said
Jayson Dallas, M.D., chief executive
officer, Rivus Pharmaceuticals. "HU6 has the potential to be the
first disease-modifying treatment for HFpEF. We look forward to
further evaluating the potential benefits of HU6 in this large and
growing patient population and sharing topline results in the
second half of 2024."
HFpEF is a chronic debilitating syndrome characterized by
severely reduced exercise capacity, which degrades quality of life.
Obesity is a major independent 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. Weight loss approaches that
involve dieting, bariatric surgery and 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.
"Given the limitations of current options for patients with
obesity-related HFpEF, novel disease-modifying treatments are
urgently needed," said Dalane W.
Kitzman, M.D., lead author of the publication and professor
of internal medicine and cardiovascular medicine at Wake Forest University School of Medicine. "As
detailed in this new publication, HU6 reduces fat, which is pivotal
to the development of HFpEF, by increasing energy expenditure while
preserving muscle. The Phase 2a trial will examine HU6's potential
to improve key outcomes in HFpEF, including increasing exercise
capacity and quality of life, reducing systemic inflammation, and
improving blood pressure and glucose metabolism."
About the Phase 2a HuMAIN
Trial
The randomized, double-blind,
placebo-controlled, parallel-group, dose-escalation Phase 2a HuMAIN
study (ClinicalTrials.gov: NCT05284617) is evaluating the safety,
tolerability, pharmacodynamics and pharmacokinetics of ascending
doses of HU6 (150 mg, 300 mg, 450 mg daily) in patients with
obesity-related HFpEF. A total of 65 study participants (37 women
and 28 men) age 30 or older with a body mass index
(BMI) >30 kg/m2 were randomized to 134 days of daily dosing
with HU6 or placebo.
The primary efficacy endpoint is weight reduction (as measured
by the change from baseline in body weight at Day 134). The key
secondary efficacy endpoint is exercise capacity (as measured by
the change from baseline in peak VO2 [mL/kg/min] during
a standardized, noninvasive cardiopulmonary exercise test at Day
134). The effects of HU6 on disease-specific quality of life,
changes in body composition and cardiac function/structure, and
markers of cardiometabolic dysfunction (e.g., changes in blood
pressure and pulse, glucose control, inflammation, lipid levels and
liver fat and liver enzymes) are also being evaluated. The study is
designed to identify the optimal dose of HU6 for Phase 3 trials.
HuMAIN is being conducted at 22 clinical sites in the United States.
About Controlled Metabolic Accelerators (CMAs)
Rivus
is advancing a new class of investigational medicines called
Controlled Metabolic Accelerators (CMAs) that have the potential to
improve metabolic health for people with obesity and
associated metabolic diseases. CMAs are oral small molecules
designed to increase resting metabolic rate, which results in
increased consumption of energy, primarily from fat. The loss in
fat mass addresses multiple cardiometabolic conditions driven by
adiposity. CMAs increase metabolism in a continuous and
imperceptible manner by leveraging the natural metabolic process of
mitochondrial uncoupling. Uncoupling accounts for 20%-40% of
resting caloric consumption. A key advantage of this mechanism for
increasing energy expenditure is that the resulting weight loss is
fat selective with preservation of muscle mass. In contrast,
caloric-restriction strategies reduce energy input and result in
loss of fat as well as muscle mass. Initial data in humans has
demonstrated that CMAs provide fat-selective weight loss, improved
insulin sensitivity, and a significant reduction in oxidative
stress and inflammation.
About HU6
HU6, an oral, once-daily investigational
medicine, 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 promotes sustained weight loss by gently, safely
and imperceptibly increasing resting metabolism, which results in
fat burn, while preserving muscle mass. Phase 2 results in patients
with a high body mass index (BMI) and metabolic
dysfunction-associated steatotic liver disease (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.1 HU6 was well
tolerated; side effects were mainly mild or moderate in
severity.
The current clinical development of HU6 is focused on metabolic
diseases with the most morbidity and greatest treatment needs:
heart failure with preserved ejection fraction (HFpEF) and
metabolic dysfunction-associated steatohepatitis (MASH)/MASLD.
About Rivus Pharmaceuticals
Rivus Pharmaceuticals,
Inc., a leader in mitochondrial biology, is dedicated to improving
metabolic health by advancing a new class of investigational
medicines called Controlled Metabolic Accelerators (CMAs). Rivus'
lead CMA is the investigational small molecule HU6 in development
to treat heart failure with preserved ejection fraction (HFpEF),
metabolic dysfunction-associated steatotic liver disease
(MASLD)/metabolic dysfunction-associated steatohepatitis (MASH) and
Type 2 diabetes. For more information, please visit
www.rivuspharma.com.
Contact:
Meredith
Mallen
Real Chemistry
mmallen@realchemistry.com
+1-516-987-2313
References
- 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. Lancet Gastroenterol
Hepatol. 2023.
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