– The IMPROVE-ISCHEMIA Phase 2 clinical trial met the primary endpoint of tolerability and safety; 8-weeks treatment with ninerafaxstat also demonstrated a statistically significant improvement in dobutamine stress-induced ischemic left ventricular (LV) dysfunction compared to placebo, as well as an increase in myocardial glucose utilization, confirming target engagement –
– Results confirm the direct anti-ischemic effect of ninerafaxstat and support further development in cardiac ischemic disorders including stable angina –
BOSTON, Nov. 12, 2023 (GLOBE NEWSWIRE) — Imbria Pharmaceuticals, Inc., a clinical stage, cardiometabolic company dedicated to developing innovative therapies designed to improve patient symptoms and function by enhancing cellular energetics, today announced positive topline results from the randomized, double-blind, placebo-controlled Phase 2 IMPROVE-ISCHEMIA trial, evaluating ninerafaxstat, a novel cardiac mitotrope and partial fatty acid oxidation (pFOX) inhibitor, in patients with chronic stable angina.
Treatment with ninerafaxstat was well tolerated and no safety signals were observed.
At 8-weeks, treatment with ninerafaxstat demonstrated clinically and statistically significant improvements in dobutamine stress-induced ischemic left ventricular (LV) wall motion abnormalities. This robust anti-ischemic effect was not dependent on changes in myocardial blood flow, consistent with a direct, metabolic mechanism of action of ninerafaxstat targeting the cardiomyocyte. In addition, a significant increase in myocardial glucose utilization compared to placebo was observed, confirming the ability of ninerafaxstat to induce a switch in substrate use to glucose, the optimal energy source in the setting of ischemia.
“The randomized, placebo-controlled IMPROVE-ISCHEMIA trial provides detailed insights into the anti-ischemic effects of ninerafaxstat in symptomatic patients with stable angina,” said Juhani Knuuti, M.D., Ph.D., Professor and Director of Turku PET Centre in Turku, Finland and chief investigator of the IMPROVE-ISCHEMIA trial. “Given the large projected future increases in the incidence of ischemic heart disease and the limited level of therapeutic innovation, there is a pressing need to address the high symptomatic burden of angina with novel effective oral therapies.”
“These topline results from IMPROVE-ISCHEMIA confirm the anti-ischemic effect of ninerafaxstat and support further development in cardiac ischemic disorders,” said Jai Patel, MRCP (U.K.), chief medical officer of Imbria. “This novel approach may have the potential to achieve optimal relief of angina and improve quality of life of patients when used alone or in combination with existing therapies.”
Imbria anticipates sharing full data from the IMPROVE-ISCHEMIA Phase 2 clinical trial at an upcoming medical conference.
About IMPROVE-ISCHEMIA
IMPROVE-ISCHEMIA (NCT04826172) is a randomized, double-blind, placebo-controlled clinical trial evaluating the safety, tolerability of ninerafaxstat in patients with stable angina and chronic coronary syndrome treated for 8-weeks on top of current antianginals. The trial further evaluated the anti-ischemic effects of ninerafaxstat through assessment of myocardial blood flow and myocardial functional response to ischemia using dobutamine stress echocardiography.
About Stable Angina
In the U.S. alone, the overall prevalence of stable angina is estimated at approximately 4% of all adults (>10 million, Tsao et al., Circulation 2023) with 500,000 new cases of angina occurring annually. Stable angina is characterized by recurrent episodes of reversible cardiac oxygen demand/supply mismatch typically resulting in pain or heaviness in the anterior chest and may be accompanied by fatigue resulting in poor quality of life.
Although cardiac ischemia is a metabolic disorder disrupting cellular energetics, there are currently no approved pharmacological therapies in the U.S. which directly address this by targeting cardiomyocyte metabolism. Pharmacological treatment of angina has traditionally focused on manipulating hemodynamics to reduce cardiac oxygen demand by lowering blood pressure, cardiac contractility, and/or heart rate using beta blockers, calcium channel antagonists, and nitrates frequently in combination. However, when titrated to effect, these agents often reach a plateau of hemodynamic suppression, where adding further dose increments or therapies with a similar hemodynamic mechanism of action confers little additive symptomatic benefit, while adverse effects increase, which may limit tolerability and prevent adequate symptom relief.
About ninerafaxstat
Our lead product candidate, ninerafaxstat, is an innovative treatment for cardiac diseases characterized by an imbalance of energy supply and demand in the heart. To maintain normal pump function and cell viability, the heart requires substantial amounts of energy, which is produced in the form of ATP. The heart normally uses two primary fuels for energy generation: fatty acids and glucose. Ninerafaxstat, a partial fatty acid oxidation (pFOX) inhibitor, acts to shift the heart’s preference from fatty acids towards glucose. This shift in metabolism leads to more efficient energy generation with the potential for improved cardiac function both at rest and during exercise.
About Imbria
Imbria is a privately held, clinical stage company developing novel therapies for patients with life-altering cardiometabolic disorders. Our clinical stage pipeline is focused on restoring or improving the cell’s ability to produce energy in cardiovascular disorders where energetic impairment is a fundamental contributor to symptoms and functional deficits. The lead product candidate, ninerafaxstat, is currently in Phase 2 clinical development in three indications: non obstructive cardiomyopathy (nHCM), stable angina, and heart failure with preserved ejection fraction (HFpEF). For additional information, please visit www.imbria.com.
Contact:
Komal Joshi
Imbria Pharmaceuticals, Inc.
kjoshi@imbria.com
