Results from the phase 2b ixCELL-DCM clinical study of Ixmyelocel-T in patients with advanced heart failure due to ischemic dilated cardiomyopathy, were presented at the American College of Cardiology's ( ACC ) 65th Annual Scientific Session and published in The Lancet.
The ixCELL-DCM study met its primary endpoint of demonstrating a reduction in the total number of all-cause deaths, cardiovascular hospitalizations, or unplanned outpatient and emergency department visits to treat acute decompensated heart failure during the 12 months following treatment with Ixmyelocel-T compared to placebo.
From a safety perspective, the incidence of adverse events, including serious adverse events, in patients treated with Ixmyelocel-T was comparable to or lower than patients in the placebo group.
The ixCELL-DCM clinical trial is a multicenter, randomized ( 1:1 ), double-blind, placebo-controlled phase 2b study to assess the efficacy, safety and tolerability of Ixmyelocel-T compared to placebo when administered via transendocardial catheter-based injections to subjects with end-stage heart failure due to ischemic dilated cardiomyopathy.
A total of 126 patients with NYHA class III or IV heart failure were randomly assigned to receive either Ixmyelocel-T or placebo, and 114 patients were treated at 28 sites in the United States.
All clinical events in the primary and secondary endpoints were adjudicated in a blinded fashion by an independent adjudication committee.
The trial met its primary endpoint with patients in the Ixmyelocel-T group having a 37% reduction in all-cause deaths, cardiovascular hospitalizations, or unplanned outpatient and emergency department visits to treat acute decompensated heart failure during the 12 months following treatment compared to the placebo group ( p=0.0344 ).
The primary endpoint was driven by a reduction in both all-cause deaths and cardiovascular hospitalizations.
In the primary endpoint without procedure-related events, 3% of patients in the Ixmyelocel-T group died and 38% had cardiovascular hospitalizations one or more times, compared to 14% and 47%, respectively, in the placebo group.
All deaths were adjudicated to be due to cardiovascular causes.
With respect to the secondary endpoints of the trial, the components of the primary endpoint were also analyzed using the Win ratio in a hierarchical manner to incorporate both the incidence and timing of the endpoint components.
The Win ratio result of 1.56 showed that more often Ixmyelocel-T was the "winner" in that the time to death, left ventricular assist device placement, heart transplantation or time to cardiovascular hospitalization was shorter for placebo-treated patients, but this difference did not reach statistical significance.
The time to first event was longer in the Ixmyelocel-T group compared to placebo, but was not statistically significant. There were no significant structural changes in left ventricle cavity size or left ventricular ejection fraction as measured by echocardiogram in either the Ixmyelocel-T or placebo groups.
Both treatment groups had an improvement in the NYHA class and six minute walk test, with no statistical difference between the groups at month 12 using last observation carried forward.
Overall, there were fewer adverse events and serious adverse events in the Ixmyelocel-T group compared to the placebo group.
Adverse events included those typically related to catheterization or injection procedures.
The ixCELL-DCM trial showed a statistically significant reduction in clinical events driven by both cardiac mortality and cardiac hospitalizations at 12 months compared to placebo.
These results are consistent with two previous phase 2a studies which showed that ischemic dilated cardiomyopathy patients treated with Ixmyelocel-T experienced fewer major adverse cardiovascular events during follow up compared to control patients.
Ixmyelocel-T is a patient-specific, expanded multicellular therapy manufactured from the patient's own bone marrow using Vericel's proprietary, highly automated, fully closed cell-processing system.
This process selectively expands the population of mesenchymal stromal cells and alternatively activated macrophages, which are responsible for production of anti-inflammatory and pro-angiogenic factors known to be important for repair of damaged tissue.
Ixmyelocel-T has been designated as an orphan drug by the U.S Food and Drug Administration ( FDA ) for use in the treatment of dilated cardiomyopathy. ( Xagena )
Source: Vericel, 2016