Longeveron's Laromestrocel Misses Primary Endpoint in ELPIS II Phase 2b Trial in Hypoplastic Left Heart Syndrome
核心洞察
Longeveron's ELPIS II Phase 2b trial of laromestrocel in 40 infants with hypoplastic left heart syndrome (搜索) missed its primary endpoint of change in right ventricular ejection fraction at 12 months.
The intent-to-treat least-squares mean difference in RVEF was -0.7 percentage points (95% CI: -7.3 to 5.9; p=0.8336), and a sponsor-defined hierarchical composite endpoint was also not statistically significant.
Laromestrocel showed a safety profile consistent with prior trials, with no new safety signals and no treatment-emergent adverse events assessed by investigators as related to the therapy.
Longeveron Inc. (NASDAQ: LGVN) reported that its Phase 2b ELPIS II trial of the investigational allogeneic mesenchymal stem cell therapy laromestrocel (Lomecel-B) failed to meet its primary efficacy endpoint in infants with hypoplastic left heart syndrome (搜索) (HLHS). The trial did not achieve a significant change from baseline in right ventricular ejection fraction (RVEF) at Month 12, with an intent-to-treat (ITT) least-squares mean difference between treatment groups of −0.7 percentage points (95% CI: −7.3 to 5.9; p=0.8336).
The company disclosed the topline results on Sept. 16, 2026, and said it is conducting additional analyses of the complete dataset and intends to discuss the results with the U.S. Food and Drug Administration 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. The agency had also advised Longeveron that RVEF alone would not be sufficient to demonstrate efficacy for regulatory approval.
Trial Design and Population
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 (NHLBI) through grants from the National Institutes of Health (NIH) (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 (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 primary endpoint was the difference between groups' change from baseline in RVEF at 12 months, assessed by cardiac magnetic resonance (CMR).
Exploratory Outcomes and Safety
In initial exploratory clinical outcomes from the as-treated analyses, there were no deaths over a 12-month period in patients who received laromestrocel, compared with one patient in the control group. Over long-term follow-up of transplant-free survival (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 also not statistically significant in the ITT population.
On safety, laromestrocel demonstrated a profile generally consistent with prior clinical trials, and no new safety signals were identified. Treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TE-SAEs) were reported in 94.1% and 64.7% of laromestrocel-treated participants, respectively, compared with 100% and 71.4% of control participants. No TEAEs or TE-SAEs were assessed by investigators as related to laromestrocel. Across Longeveron's clinical development programs, 644 participants have been treated to date.
"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," said Sunjay Kaushal, M.D., Ph.D., Professor of Surgery, Cardiovascular and Thoracic Surgery at University of Nevada, Las Vegas.
Disease Burden in HLHS
HLHS 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, creating 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. Despite staged surgical palliation, long-term mortality and morbidity remain substantial, with progressive right ventricular dysfunction representing a major contributor to adverse outcomes.
Strategic Review and Pipeline Priorities
Longeveron announced it has initiated a process to review all 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, the company will look to implement cash conservation measures to optimize cost containment.
"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 (搜索). We will work with our advisors to evaluate all options to maximize shareholder value."
The company said it intends to pursue funding sources and other potential revenue opportunities to advance laromestrocel in longevity and Aging-related Frailty (搜索). Results from a Phase 2b clinical trial demonstrated that intravenous laromestrocel improved the physical condition of patients with age-related clinical frailty after nine months compared to placebo; those results were published in Cell Stem Cell in February 2026. Based on these results, Longeveron announced in August 2026 that it was selected from over 600 worldwide applicants to advance to the final phase of the XPRIZE Healthspan competition as a Milestone 2 Awardee team, receiving a $1,000,000 Milestone 2 Award toward a future competition clinical trial, with the opportunity to compete for a Grand Prize of up to $81 million.
Laromestrocel is a living cell product made from specialized cells isolated from the bone marrow of young, healthy adult donors. These cells, known as mesenchymal stem cells (搜索), are essential to the human endogenous biological repair mechanism and may respond to sites of injury or disease and secrete bioactive factors that are immunomodulatory and regenerative. Longeveron is pursuing four pipeline indications: HLHS, Alzheimer's disease (搜索), Pediatric Dilated Cardiomyopathy (搜索) (DCM) and Aging-related Frailty (搜索). The laromestrocel development programs have received five FDA designations: Orphan Drug, Fast Track and Rare Pediatric Disease designations for the HLHS program, and Regenerative Medicine Advanced Therapy (RMAT) and Fast Track designations for the Alzheimer's disease program.