Longeveron Stem Cell Phase 2b for Hypoplastic Left Heart Syndrome Misses Primary Endpoint
In the 40-infant randomized, double-blind trial, patients received a single intramyocardial dose. It did not improve right ventricular ejection fraction at 12 months.
Key Points
- Longeveron reported that the Phase 2b ELPIS II trial of laromestrocel in hypoplastic left heart syndrome did not meet its primary endpoint of improvement in right ventricular ejection fraction at 12 months.
- Exploratory analyses showed no new safety signals, with additional clinical outcome data under review ahead of discussions with the FDA on possible next steps.
- The company said it is reviewing strategic options, pursuing cost containment, and continuing to look for funding opportunities to advance laromestrocel in aging-related frailty.
Longeveron announced topline results from ELPIS II, its Phase 2b clinical trial evaluating the investigational stem cell therapy laromestrocel as an adjunct to Stage 2 palliative surgery in 40 infants with hypoplastic left heart syndrome (HLHS). The trial did not meet its primary efficacy endpoint of change from baseline in right ventricular ejection fraction (RVEF) at Month 12. In the intent-to-treat population, the least-squares mean difference between treatment groups was −0.7 percentage points (95% CI: −7.3 to 5.9; p=0.8336).
Initial exploratory clinical outcomes in the as-treated analyses include:
- Over a 12-month period, there were no deaths in patients that received laromestrocel, compared to one patient in the control group.
- Over a long-term follow up of transplant-free survival of up to five years across all patients, the laromestrocel arm had one event out of 17 patients versus two events out of 21 patients in the standard-of-care arm.
- Hospitalization burden was similar between arms.
- Adjudicated Major Adverse Cardiovascular Events (MACE) were approximately 31% fewer in the laromestrocel arm, with 12 events in the treated arm versus 19 events in the untreated arm. However, the negative binomial analysis was not statistically significant.
- A sponsor-defined exploratory hierarchical composite endpoint consisting of all-cause mortality and duration of inpatient hospitalization was not statistically significant in the intent-to-treat population.
Laromestrocel demonstrated a safety profile generally consistent with prior clinical trials, and no new safety signals were identified in the study. Treatment-emergent adverse events and treatment-emergent serious adverse events were reported in 94.1% and 64.7% of laromestrocel-treated participants, respectively, compared with 100% and 71.4% of control participants. No treatment-emergent adverse events or treatment-emergent serious adverse events were assessed by investigators as related to laromestrocel.
The company is conducting additional analyses of the complete dataset and intends to discuss the results with the FDA to determine potential next steps for the HLHS development program. FDA previously indicated its willingness to meet with the company following completion of the study to discuss the results and potential paths forward.
Sunjay Kaushal, M.D., Ph.D., Professor of Surgery, Cardiovascular and Thoracic Surgery at University of Nevada, Las Vegas commented: “There remains a significant unmet medical need to boost the survival of the babies undergoing standard of care surgeries that still have only a 50-60% survival rate to adolescence with approximately 20% requiring heart transplant. ELPIS II provides evidence of the safety of using stem cells to address this unmet need.”
“Since its founding, Longeveron has advanced the stem cell therapy laromestrocel, completed multiple clinical trials and built a robust intellectual property portfolio,” said Stephen H. Willard, Chief Executive Officer of Longeveron. “The ELPIS II results continue to build our body of knowledge of laromestrocel for which we see significant promise across multiple indications, particularly in longevity and Aging-related Frailty. We will work with our advisors to evaluate all options to maximize shareholder value.”
Strategic Review and Cost Containment
The company said it has initiated a process to review options with the goal of maximizing shareholder value and intends to engage an investment bank to act as a strategic advisor. In conjunction with that process, it said it will look to implement cash conservation measures to optimize cost containment.
Frailty Program
The company said it intends to pursue funding sources and other potential revenue opportunities to advance laromestrocel in longevity and aging-related frailty. It said results from a Phase 2b clinical trial showed that intravenous laromestrocel improved the physical condition of patients with age-related clinical frailty after nine months, compared to placebo. These results were published in Cell Stem Cell in February 2026.
Longeveron also said in August 2026 that it was selected from more than 600 worldwide applicants to advance to the final phase of the XPRIZE Healthspan competition as a Milestone 2 Awardee team. The company received the $1,000,000 Milestone 2 Award to be used toward the future competition clinical trial in accordance with the XPRIZE competition rules, with the opportunity to compete for the XPRIZE Grand Prize of up to $81 million.
Trial and Product Background
ELPIS II is a Phase 2b, randomized, double-blind, multicenter, two-arm trial conducted by Longeveron in collaboration with the National Heart, Lung, and Blood Institute through grants from the National Institutes of Health (NCT04925024). A total of 40 infants with HLHS were randomized 1:1 to receive a single intramyocardial dose of laromestrocel administered during Stage 2 palliative surgery, either bidirectional Glenn or hemi-Fontan procedure, or standard-of-care surgery alone, and were followed for 12 months. Long-term follow-up for transplant-free survival is planned for up to 5 years.
The trial’s primary endpoint was the difference between groups’ change from baseline in RVEF at 12 months, assessed by cardiac magnetic resonance. As previously disclosed, FDA advised Longeveron that RVEF alone would not be sufficient to demonstrate efficacy for regulatory approval.
Hypoplastic left heart syndrome is a rare congenital heart defect that affects approximately 1,000 infants per year in the U.S. Infants with HLHS are born with an underdeveloped left ventricle, which creates a life-threatening condition due to the heart’s inability to pump adequate amounts of blood throughout the body. Current treatment requires infants to undergo a complex three-stage heart reconstruction surgery process over the first five years of life.
Laromestrocel is a living cell product made from specialized cells isolated from the bone marrow of young, healthy adult donors. These specialized cells, known as mesenchymal stem cells (MSCs), are described by the company as part of the body’s biological repair mechanisms. Longeveron’s lead investigational product is laromestrocel, an allogeneic (donor derived) MSC therapy product.
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