Data Readout

FDA tells Longeveron its HLHS trial's endpoint can't prove efficacy, mid-study

The agency rejected ejection fraction as sufficient in ELPIS II and stripped the study of pivotal status, leaving Longeveron to defend a new composite endpoint once August's blinded data unblind.

By AppliedXLJuly 14, 2026Trial NCT04925024

Executive Summary

Before its data even read out, this trial lost the primary endpoint it was designed around, after the FDA told the sponsor that endpoint cannot demonstrate efficacy on its own.
The agency now declines to call the study pivotal, so a positive result on the original endpoint would no longer be enough to move toward approval without further agreement on a new analysis plan.
The FDA named a narrower set of objective outcomes it would accept as evidence of benefit, and the sponsor is capturing all of them, but has not yet secured the agency's sign-off on how they will be combined into a single endpoint.
A blinded, NIH-run interim analysis is already underway inside the trial, a constraint that kept the FDA from settling on a new endpoint before the study finishes enrollment and data collection.
No other cell therapy in this rare congenital heart defect has produced a resolved efficacy result to benchmark against, so this readout would be the first of its kind regardless of which endpoint ultimately gets used.

What the FDA said

Longeveron Inc. (NASDAQ: LGVN) said the FDA told the company its ELPIS II primary endpoint, change in right ventricular ejection fraction (RVEF), is not an appropriate measure to demonstrate efficacy in hypoplastic left heart syndrome (HLHS). RVEF is the trial's registered primary outcome measure. Longeveron said it agreed with the FDA that RVEF alone is insufficient and came prepared to discuss alternative endpoints, but the agency said a new primary endpoint could not be agreed to while the trial remains ongoing, because an interim analysis mandated by the National Institutes of Health is underway and the company remains blinded to it. Without a settled efficacy endpoint, the FDA told Longeveron it no longer refers to ELPIS II as pivotal, a designation the agency had used in a 2024 Type C meeting. Longeveron+1

The trial

ELPIS II (NCT04925024) is a multicenter, randomized, controlled Phase 2b trial testing laromestrocel (LOMECEL-B), an allogeneic mesenchymal stem cell therapy, as an adjunct to Stage II surgical palliation in infants with HLHS. The trial enrolled 40 patients across twelve U.S. sites, sponsored by Longeveron with the National Heart, Lung, and Blood Institute as a collaborator. It moved to Active, not recruiting status in June 2025 once enrollment reached target. The trial's primary completion date has moved four times since 2024, most recently landing on June 30, 2026, with the overall study completion date set at August 31, 2026. Longeveron has guided to an August 2026 top-line readout in each of its last several disclosures. NCT04925024+1

What would count as evidence

The FDA told Longeveron that only the most objective measures could be informative of efficacy in this setting: all-cause mortality, cardiac transplant-free survival, cardiac transplantation events, and well-defined major adverse cardiac events (MACE). Longeveron said it is capturing all of these measures in ELPIS II, along with additional secondary measures, and intends to submit a Sponsor Statistical Analysis Plan proposing a composite primary endpoint built from them for FDA review. The company said it remains open to filing a Biologics License Application on the strength of the ELPIS II results, and that the FDA agreed to reconvene once the study completes to discuss results and a potential path forward. No submitted analysis plan, and no FDA response to one, has been disclosed. Longeveron

The competitive field

No trial shares laromestrocel's modality-indication pairing with a resolved efficacy result to benchmark against. The two nearest precedents are Longeveron's own earlier mesenchymal-cell studies in HLHS, an initial Lomecel-B trial and a separate mesenchymal-cell study, both single- or early-phase without a controlled comparator. The only other active interventional trials in HLHS use different modalities, a protein-based cardiac patch and surfactant therapy, neither of which is a cell therapy and neither of which targets the same treatment window. ELPIS II is one of just two active industry-sponsored trials in this indication tracked in current competitive searches, alongside a Baxter adhesion-prevention device trial in broader congenital heart disease. The rarity of the disease and the narrowness of the field mean this readout, whatever endpoint ultimately governs it, would be the first controlled cell-therapy result in HLHS regardless of outcome.

The regulatory backdrop

Laromestrocel already holds FDA Rare Pediatric Disease and Orphan Drug designations for HLHS, both granted in 2021. Those designations reflect the disease's rarity and unmet need rather than any signal about whether this trial's data will be sufficient for approval. The substantive regulatory event is the endpoint rejection itself: a mid-trial determination that the study's registered primary outcome cannot carry an efficacy claim, delivered while enrollment and the underlying interim analysis are locked.

This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.