In PH-HFpEF Trial, Switch to Oral Levosimendan a Success, Data Show
Move from weekly infusions to daily oral therapy well-tolerated by patients
Switching from weekly infusions of levosimendan to a daily oral version of the experimental medication was well-tolerated among people with pulmonary hypertension and heart failure with preserved ejection fraction (PH-HFpEF), according to new trial data.
That data, from the open-label extension phase of the HELP Phase 2 clinical trial (NCT03541603), was presented this month at the Heart Failure Society of America (HFSA) Scientific Sessions 2022. The presentation was titled “The Transition from Chronic Intravenous to Oral Levosimendan Is Safe and Effective in Patients with Pulmonary Hypertension with Heart Failure and Preserved Ejection Fraction.”
According to Tenax Therapeutics, the company developing levosimendan in North America, these results back further clinical testing of the therapy’s oral formulation.
“The observed safety and effectiveness supports the use of oral levosimendan in Phase 3 testing in patients with PH-HFpEF, a devastating disease with no effective treatment options available,” Chris Giordano, Tenax’s CEO, said in a press release.
Added Stuart Rich, MD, chief medical officer at Tenax: “This important finding confirms that these patients with advanced PH-HFpEF can be treated successfully with daily oral levosimendan while avoiding the risks associated with weekly IV [infusion] treatments. We are very encouraged to see these effects in patients who have received levosimendan therapy for over two years.”
In PH-HFpEF, the heart beats normally, but its muscles are too stiff and weak to properly pump blood out to the body. Results from the HELP trial suggested treatment with levosimendan improved exercise tolerance and some measures of heart function in people with PH-HFpEF. It is thought to work by reducing the amount of blood putting pressure on the circulatory system.
Investigating oral levosimendan
After the initial study, participants in HELP had the option to enroll in an open-label extension, in which all were treated with levosimendan — administered intravenously or via infusion into the bloodstream, once per week.
As part of the study’s extension, participants were offered the opportunity to switch from infusions to once-daily oral treatment. The purpose of this sub-study was to test the hypothesis that switching to oral treatment would safely maintain levosimendan’s effectiveness while reducing the risk of infusion-related infections and clotting problems.
A total of 18 participants transitioned from infusions to oral treatment over 6–8 weeks, though results for efficacy measures were not available for all of these PH-HFpEF patients. The patients had been on infused levosimendan for an average of about 18 months.
Available data showed that switching to oral levosimendan led to an increase in mean heart rate, by 4.9 beats per minute, and in systolic arterial blood pressure, by 4.1 mm Hg.
The mean distance participants could walk in six minutes — a common measure of exercise capacity — increased by 13.1 meters (nearly 43 feet) after switching to oral treatment. Levels of two markers of heart damage, BNP and NT-proBNP, decreased by 133.3 and 239.4 picograms per deciliter, respectively.
Improvements also were reported for average scores on the Kansas City Cardiomyopathy Questionnaire, which assesses the impact of heart failure symptoms in daily life.
According to Tenax, these results indicate that “oral levosimendan at 3-4 mg/day may provide a superior formulation for chronic use in PH-HFpEF patients when compared to the intravenous administration of levosimendan.”
“We are grateful to the patients and their families, our investigators, and all the research staff who continue participating in this open label extension,” Giordano said.