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Longeveron starts strategic review after laromestrocel failure to improve heart function in HLHS infants

Longeveron starts strategic review after laromestrocel failure to improve heart function in HLHS infants

Longeveron Inc.'s (Nasdaq: LGVN) laromestrocel failed to improve right ventricular function in infants with hypoplastic left heart syndrome (HLHS), according to topline results from the ELPIS II Phase IIb trial, prompting a review of strategic alternatives. Longeveron posted the results on September 16, 2026.

HLHS affects approximately 1,000 infants per year in the US. The underdeveloped left ventricle forces the right ventricle to sustain systemic circulation through a complex three-stage surgical palliation process. Even with surgery, only about 50%-60% of patients survive to adolescence, with roughly 20% requiring heart transplant.

Laromestrocel is an allogeneic mesenchymal stem cell (MSC) therapy derived from the bone marrow of healthy adult donors. The cells are hypothesized to secrete bioactive factors with anti-inflammatory and pro-vascular regenerative effects, potentially supporting right ventricular repair when delivered as a single intramyocardial injection during Stage 2 palliative surgery. The FDA had previously advised Longeveron that right ventricular ejection fraction (RVEF) alone would not be sufficient to demonstrate efficacy for regulatory approval.

In the intent-to-treat (ITT) population of the randomized, double-blind, multicenter trial enrolling 40 infants, the least-squares mean difference in RVEF change from baseline at 12 months was −0.7 percentage points (95% CI: −7.3 to 5.9; p=0.8336). A sponsor-defined exploratory hierarchical composite endpoint of all-cause mortality and inpatient hospitalization duration was also not statistically significant in the ITT population. Exploratory as-treated analyses showed zero deaths in the laromestrocel arm versus one in the control group over 12 months, and approximately 31% fewer adjudicated major adverse cardiovascular events (MACE) — 12 versus 19 events — though the negative binomial analysis for MACE did not reach statistical significance. Longeveron said no new safety signals were identified and no treatment-emergent adverse events were assessed as related to laromestrocel.

The trial was conducted in collaboration with the National Heart, Lung, and Blood Institute (NHLBI) through National Institutes of Health (NIH) grants. The independent Data Monitoring Committee had cleared the study to continue following its final prespecified safety review in May 2026. Earlier in the year, the FDA had advised Longeveron during a Type C meeting that right ventricular ejection fraction alone would not be considered an appropriate efficacy endpoint for approval, prompting the company to develop a statistical analysis plan incorporating a composite clinical endpoint ahead of the readout.

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The failure puts the HLHS BLA filing — which Longeveron had positioned as its primary near-term regulatory milestone — on hold pending FDA discussions. The company said it intends to meet with the FDA to determine potential next steps, and will conduct additional analyses of the complete dataset. The FDA had previously expressed willingness to meet following study completion to discuss results and potential paths forward.

With HLHS in doubt, Longeveron said it will shift focus to laromestrocel's aging-related frailty program, where Phase IIb data published in Cell Stem Cell in February 2026 showed improved physical function at nine months versus placebo. The company also holds Regenerative Medicine Advanced Therapy (RMAT) and Fast Track designations for laromestrocel in mild Alzheimer's disease, with a Phase II/III design aligned with the FDA following a Type B meeting in March 2025. Longeveron said it has initiated cost containment measures and will engage an investment bank to explore all options to maximize shareholder value. As of June 30, 2026, the company reported USD 10.1 million in cash, which it had projected would fund operations into Q4 2026.


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