Heart Failure with Preserved Ejection Fraction
Heart failure with preserved ejection fraction (HFpEF) is a growing global epidemic with no approved therapies. HFpEF often leads to impaired daily functioning, low exercise tolerance and frequent hospitalizations.
Heart Failure with Preserved Ejection Fraction (HFpEF) and the Role of Nitric Oxide Deficiency
Patients with HFpEF have clinical signs and symptoms that include difficulty breathing, swelling of the legs, congestion in the lungs and enlargement of the heart. These patients are often unable to participate in physical activities, have impaired quality of life, and are frequently hospitalized for heart failure symptoms. Low exercise capacity is a significant cause of poor health in HFpEF patients and substantially affects patients’ day-to-day functioning. HFpEF patients generally suffer from multiple co-morbid conditions including type 2 diabetes, chronic kidney disease, metabolic syndrome, coronary artery disease, obesity and hypertension.
There are no approved therapies to treat HFpEF. Lifestyle modifications such as diet and exercise are recommended but are often ineffective. Current disease management strategies are based on treating the related medical conditions that often occur with HFpEF such as diabetes, hypertension, chronic kidney disease, chronic pulmonary disease, obesity and coronary artery disease.
HFpEF is associated with nitric oxide deficiency, resulting in endothelial dysfunction, chronic microvascular inflammation and decreased blood flow to the heart and other muscles in the body. These effects may lead not only to increased heart stiffness (fibrosis) and cardiac dysfunction, but also play a role in limiting oxygen extraction in skeletal muscle which is a potential contributor to exercise intolerance symptoms in HFpEF patients.
We believe our investigational, oral product candidate, praliciguat, has the potential to provide both short- and long-term beneficial effects for patients with HFpEF. By enhancing impaired nitric oxide signaling in the heart and systemic circulation, we believe praliciguat has the potential to improve coronary blood flow as well as oxygen delivery to skeletal muscle. Furthermore, we believe longer-term treatment with praliciguat has the potential to reduce cardiac stiffness, microvascular inflammation and fibrosis. We believe praliciguat may have a positive impact on patient symptoms, including improving exercise capacity and day-to-day functioning, as well as reduce hospitalizations and mortality in this underserved patient population.
Praliciguat was granted Fast Track Designation for the treatment of HFpEF by the U.S. Food and Drug Administration and is currently in a Phase 2 proof-of-concept trial, CAPACITY-HFpEF, that is expected to enroll approximately 184 patients. We expect results from this study in the second half of 2019.
Facts & Figures:
- Heart failure remains a rising global epidemic with an estimated prevalence of approximately 38 million individuals globally. HFpEF comprises 44% to 72% of new heart failure diagnoses.
- Heart failure is the most common cause of hospitalization in Medicare patients and represents approximately one million discharges per year.
- Between 1987 and 2001, the average prevalence of HFpEF hospitalizations increased from 38% to 54%.
- Admitted patients with HFpEF have a 50% chance of re-hospitalization for heart failure within six months.
- Mortality rates over five years for patients diagnosed with HFpEF have been reported to range from 55% to 74%.