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. That 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.

Future Phase 3 Development

Based on the HELP Study results, we received agreement from the FDA to conduct a Phase 3 study of levosimendan in PH-HFpEF patients for regulatory approval. An important advance will be a switch from the intravenous form of levosimendan, which was used in the Phase 2 trial, to an oral formulation of levosimendan for Phase 3. We are currently conducting an IV to oral transition study in the patients who have been receiving weekly IV infusions from our HELP Study extension, which should provide us guidance on the optimal dosing regimen for our Phase 3 trial.