Longeveron’s laromestrocel missed the Phase 2b ELPIS II primary endpoint in infants with HLHS, while exploratory outcomes showed numerical differences.
Written By: Kirti Kumbhar, M. Pharm (QA)
Reviewed By: Pharmacally Editorial Team
Longeveron reported topline results from the Phase 2b ELPIS II trial evaluating laromestrocel as an adjunct to Stage 2 palliative surgery in 40 infants with hypoplastic left heart syndrome (HLHS). The study did not meet its primary efficacy endpoint, which assessed the change from baseline in right ventricular ejection fraction (RVEF) at Month 12.
In the intent-to-treat (ITT) population, the least-squares mean difference between the treatment groups was −0.7 percentage points (95% CI, −7.3 to 5.9; p=0.8336).
HLHS and Laromestrocel Overview
HLHS is a rare, life-threatening congenital heart defect in which the left ventricle is severely underdeveloped, limiting the heart’s ability to provide adequate systemic blood flow. Infants with HLHS undergo a series of three staged reconstructive surgeries early in life.
Despite surgical palliation, progressive right ventricular dysfunction remains an important contributor to long-term morbidity and mortality. The condition affects approximately 1,000 infants in the U.S. each year.
Laromestrocel is a living cell product containing mesenchymal stem cells (MSCs) isolated from the bone marrow of young, healthy adult donors. The cells may exert immunomodulatory and regenerative effects through secretion of bioactive factors, with potential anti-inflammatory and pro-vascular activity.
Exploratory Analyses Showed Numerical Differences
Although the primary efficacy endpoint was not met, exploratory as-treated analyses identified numerical differences across several clinical outcomes.
No deaths occurred among patients who received laromestrocel during the first 12 months, compared with one death in the control group. During long-term follow-up of transplant-free survival, extending up to five years, one event occurred among 17 laromestrocel-treated patients compared with two among 21 patients receiving standard care.
Hospitalization burden was similar between groups. Adjudicated major adverse cardiovascular events (MACE) occurred approximately 31% less frequently in the laromestrocel group, with 12 events compared with 19 in the control group. However, the negative binomial analysis was not statistically significant. A sponsor-defined exploratory composite endpoint combining all-cause mortality and duration of inpatient hospitalization also failed to reach statistical significance in the ITT population.
Safety Profile Remained Consistent with Prior Trials
Laromestrocel showed a safety profile generally consistent with previous clinical trials, and no new safety signals emerged in ELPIS II.
Treatment-emergent adverse events occurred in 94.1% of laromestrocel-treated participants and 100% of controls. Treatment-emergent serious adverse events occurred in 64.7% and 71.4%, respectively. Investigators did not assess any treatment-emergent adverse event or serious adverse event as related to laromestrocel. Across Longeveron’s clinical programs, 644 participants have received the therapy to date.
ELPIS II Trial Design
ELPIS II was a randomized, double-blind, multicenter Phase 2b trial conducted in collaboration with the National Heart, Lung, and Blood Institute (NHLBI) through grants from the National Institutes of Health. The 40 infants were randomized 1:1 to receive a single intramyocardial dose of laromestrocel during Stage 2 palliative surgery, consisting of a bidirectional Glenn or hemi-Fontan procedure, or standard-of-care surgery alone. Patients were followed for 12 months, with long-term transplant-free survival follow-up planned for up to five years.
FDA to Review Results and Potential Path Forward
The FDA had previously advised that RVEF alone would not be sufficient to demonstrate efficacy for regulatory approval. Longeveron plans to complete additional analyses of the full dataset and meet with the agency to discuss the results and potential paths forward for the HLHS development program.
Company Shifts Focus to Cost Control and Aging Programs
Meanwhile, Longeveron has begun reviewing strategic options and plans to implement cash-conservation measures. The company also intends to pursue funding and other revenue opportunities to advance laromestrocel in longevity and aging-related frailty. Prior Phase 2b results in aging-related clinical frailty showed improved physical condition after nine months compared with placebo, with findings published in Cell Stem Cell in February 2026.
Reference
Longeveron Announces Topline Results from ELPIS II Phase 2b Clinical Trial Evaluating Laromestrocel as a Potential Treatment for Hypoplastic Left Heart Syndrome (HLHS), Longeveron, 16 September 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
Kirti Kumbhar (LinkedIn) is an M.Pharm graduate with experience in Quality Assurance at Lupin Limited and a strong interest in clinical research, regulatory affairs, and Trial Master File (TMF) management. She has developed knowledge of regulatory documentation, quality systems, compliance, and healthcare research through her professional experience. Passionate about clinical development and continuous learning, Kirti is committed to supporting high-quality healthcare documentation, regulatory excellence, and research-driven healthcare advancements.