Clinical Development
The Hemodynamic Evaluation of Levosimendan in Patients with PH-HFpEF (HELP) Trial

WHO Group 2 : Pulmonary Hypertension with Left Heart Disease

The HELP Trial was a Phase 2 study designed to evaluate the hemodynamic effects of levosimendan at rest, during exercise, and on exercise capacity after 6 weeks of treatment in patients with advanced PH-HFpEF. The initial part of the trial included a heart catheterization at rest and exercise before and after receiving levosimendan for 24 hours. Following 24 hours of IV administration of levosimendan showed a marked effect in lowering the PCWP and the central venous pressure. The second part was a randomized placebo-controlled design to test if these effects would be sustained over 6 weeks, and result in an improvement in exercise capacity as determined by a 6 minute walk test.  After 6 weeks the patients who received the levosimendan had sustained hemodynamic effects and an improvement in exercise capacity, while the patients who received placebo had no change in hemodynamics and a worsening in exercise capacity. This was the first time that any treatment of PH-HFpEF showed sustained beneficial effects.

We subsequently conducted an IV to oral transition study in the patients who had received weekly IV infusions during our HELP Study extension. This study provided us with guidance on the optimal dosing regimen for Phase 3 development.

Future Phase 3 Development

Based on the HELP Study results, we received agreement from the FDA to conduct a Phase 3 development program of levosimendan in PH-HFpEF patients that would be adequate to support regulatory approval.