Longeveron Heart Defect Study Missed Main Endpoint, but Analysis Found Fewer Serious Cardiac Events in Infants

Rare Daily Staff

Longeveron said an updated analysis of its experimental cell therapy laromestrocel found fewer major adverse cardiac events in infants with a rare, life-threatening heart defect, offering a potential path forward for a development program whose latest study failed to meet its main goal.

Hypoplastic left heart syndrome, or HLHS, is a congenital heart defect in which infants are born with an underdeveloped left side of the heart, limiting its ability to pump blood throughout the body. Treatment for HLHS involves a complex series of three operations during the first several years of life. Despite these surgeries, children remain at substantial risk of serious complications and death, with progressive weakness of the right ventricle contributing to poor outcomes.

Laromestrocel is an experimental cell therapy made from mesenchymal stem cells isolated from the bone marrow of young, healthy adult donors. These cells may support tissue repair and influence inflammation. Longeveron believes laromestrocel could help repair tissue and support blood vessel formation.

The 40-infant phase 2b trial, called ELPIS II, tested whether adding laromestrocel to surgery could improve outcomes for children with HLHS. The company reported eight major adverse cardiac events in the standard-care group, compared with one in the laromestrocel group. The difference reached statistical significance on a prespecified secondary measure.

The finding does not change the trial’s previously reported failure to meet its primary endpoint of improving the pumping function of the heart’s right ventricle after 12 months. Longeveron said it plans to request a meeting with the U.S. Food and Drug Administration to discuss the results and possible next steps.

ELPIS II randomly assigned 40 infants to receive either standard surgery alone or surgery plus a single injection of laromestrocel into the heart muscle. The treatment was administered during the second of the staged operations used to help children with HLHS survive.

The trial’s main measure was right ventricular ejection fraction—the proportion of blood the heart’s right pumping chamber pushes out with each beat. In children with HLHS, that chamber must take on the work of pumping blood to the body.

Scans taken both before treatment and at 12 months were available for 28 of the 40 infants. Average ejection fraction declined by 2.6 percentage points in the standard-care group and 3.3 percentage points in the treatment group, with no statistically significant difference between them.

The updated analysis focused on clinical events rather than that imaging measure. In addition to the major adverse cardiac events finding, Longeveron reported that nine infants receiving standard care experienced at least one event in a broader “major cardiac event” category, compared with three receiving laromestrocel. The groups experienced 22 and three total events, respectively.

Longeveron reported no serious adverse events attributed to laromestrocel during the 12-month follow-up. The standard-care group had one death and one ventricular assist device implantation; neither outcome was reported in the treatment group.

The company said the FDA had previously advised it that an improvement in right ventricular ejection fraction alone would not be sufficient to demonstrate effectiveness for approval. Longer-term follow-up is planned for up to five years to assess survival without a heart transplant. The study was conducted in collaboration with investigators supported by the National Institutes of Health.

The results are scheduled for presentation November 8 at the American Heart Association’s Scientific Sessions in Chicago.