Longeveron reports fewer major cardiac events with laromestrocel in its Phase 2b HLHS trial, although the study missed its primary RVEF endpoint.
Written By: Creola Gonsalves, MS Biotech
Reviewed By: Pharmacally Editorial Team
Longeveron reported statistically significant reductions in major adverse cardiac events (MACE) with its investigational cell therapy laromestrocel in infants with hypoplastic left heart syndrome (HLHS). However, the Phase 2b ELPIS II trial missed its primary endpoint of improving right ventricular ejection fraction at 12 months, leaving the treatment’s potential clinical benefit to be evaluated through further regulatory discussions.
Secondary Endpoint Shows Fewer Cardiac Events
The updated analysis of ELPIS II showed one major adverse cardiac event in the laromestrocel arm compared with eight in the standard-of-care (SoC) arm, a statistically significant difference (P=0.043). The trial also recorded fewer total major cardiac events among infants receiving laromestrocel, with three events versus 22 in the SoC group.
Longeveron developed laromestrocel as an investigational adjunct to Stage II palliative surgery for HLHS, a rare congenital heart defect that leaves the left ventricle severely underdeveloped. The findings suggest a potential reduction in postoperative cardiac complications, although the missed primary endpoint limits conclusions about the therapy’s overall efficacy.
Primary Endpoint Remains Unmet
ELPIS II was a randomized, double-blind, multicenter Phase 2b trial involving 40 infants with HLHS. Participants received either a single intramyocardial dose of laromestrocel during Stage II surgical palliation or standard-of-care surgery alone, followed by 12 months of monitoring.
The primary endpoint measured the change from baseline in right ventricular ejection fraction (RVEF) at Month 12 using cardiac magnetic resonance imaging. Among the 28 infants with available baseline and Month 12 measurements, mean RVEF declined by 2.6 percentage points in the SoC group and 3.3 percentage points in the laromestrocel group. The baseline-adjusted difference was −1.36 percentage points (95% confidence interval, −8.0 to 6.7; P=0.68), showing no statistically significant treatment benefit on the primary endpoint.
The secondary analysis recorded at least one major cardiac event in nine infants receiving SoC and three receiving laromestrocel. The total event rate was 0.261 versus 0.041 per 100 person-days, respectively, with a reported rate ratio of 0.16 (95% CI, 0.030–0.52; P less than 0.001). Tricuspid regurgitation events or valve surgery occurred five times in the SoC arm and not at all in the laromestrocel arm (P=0.066). One death and one ventricular assist device implantation were recorded in the SoC group, compared with neither event in the treatment group.
Safety Profile and Clinical Significance
Laromestrocel showed a favorable safety and tolerability profile through 12 months, with no treatment-related serious adverse events identified, according to Longeveron.
The therapy, also known as Lomecel-B, contains allogeneic mesenchymal stem cells isolated from the bone marrow of young, healthy adult donors. These cells may influence inflammatory responses, tissue repair and regenerative signaling, although the trial does not establish which mechanisms, if any, account for the observed differences in cardiac events.
The findings warrant further investigation but require cautious interpretation. The study enrolled only 40 infants, and the statistically significant MACE result represents a secondary endpoint based on a small number of events. The available results do not establish a definitive clinical benefit or demonstrate improved long-term survival.
FDA Discussion and Next Milestones
Longeveron plans to request a meeting with the U.S. Food and Drug Administration to discuss the updated findings and determine potential next steps for the HLHS program. The company has previously disclosed that the FDA advised that RVEF alone would not be sufficient to demonstrate efficacy for regulatory approval.
The ELPIS II results have also been selected for a late-breaking science podium presentation at the American Heart Association’s 2026 Scientific Sessions in Chicago. The presentation is scheduled for November 8, 2026.
Long-term follow-up for transplant-free survival is planned for up to five years. These data may help clarify whether the reduction in cardiac events translates into sustained clinical benefit for infants undergoing staged surgical palliation.
Reference
Longeveron Announces Updated Results from ELPIS II Phase 2b Clinical Trial Evaluating Laromestrocel as a Potential Treatment for Hypoplastic Left Heart Syndrome (HLHS), Longeveron, 26 October 2026
Evaluation of Lomecel-B™ Injection in Patients with Hypoplastic Left Heart Syndrome (HLHS): A Phase IIb Clinical Trial. (ELPIS II), ClinicalTrials.gov ID NCT04925024
About the Writer
Creola Gonsalves (Linkedin) is an M.S. Biotechnology postgraduate with a strong interest in clinical research, evidence interpretation, and healthcare writing, with a focus on translating life-science knowledge into meaningful real-world insights.
She is trained in Good Clinical Practice (GCP), clinical research principles, and critical interpretation of randomized clinical trials, with certifications from NIH and Stanford University.
Her research background in biotechnological applications and microbial research strengthens her ability to understand scientific evidence and develop clear, accurate, and research-driven healthcare content.