Regulators fast-track gene editing for neonatal liver disease

“RMAT designation represents an important validation of ECUR-506 and the clinical data generated to date in neonatal onset OTC deficiency”Joe Truitt, CEO of iECURE

The FDA's RMAT designation provides intensive guidance and expedited review throughout ECUR-506's development, complementing the company's recent alignment with the agency on primary and secondary efficacy endpoints for the OTC-HOPE study that could support a Biologics License Application. Meanwhile, the UK's Innovative Licensing and Access Pathway has selected ECUR-506 as one of only three investigational products under its relaunched programme, all focused on rare diseases, making it the sole end-to-end access pathway globally to integrate coordinated engagement across regulatory authorities, health technology assessment bodies, and healthcare delivery partners.

»RMAT designation represents an important validation of ECUR-506 and the clinical data generated to date in neonatal onset OTC deficiency,« said Joe Truitt, chief executive officer of iECURE. »Building on our alignment with the FDA on the OTC-HOPE study design, this milestone provides a clear and actionable regulatory path forward.«

OTC deficiency is a rare genetic disorder of the urea cycle in which ammonia – a toxic waste product generated during protein breakdown – accumulates in the blood. Newborns with neonatal onset disease experience hyperammonemia shortly after birth, manifesting as lethargy, poor feeding, and vomiting that can rapidly progress to seizures, brain damage, coma, and death without intervention. Current management relies on dialysis during acute crises, followed by lifelong ammonia scavenger medications and severe protein restriction, yet breakthrough hyperammonemic episodes often occur despite medical management, leading clinicians to recommend liver transplantation within the first year of life. While curative, transplantation carries substantial risks, including graft failure and increased susceptibility to malignancy and infection from prolonged immunosuppression.

“Our team is highly encouraged to see this baby, who after having experienced two spikes in blood ammonia levels before three and a half months of age, reach a point where he no longer needs ammonia scavengers and is eating age-appropriate levels of protein for a baby of his age”Julien Baruteau, PI at Great Ormond Street Hospital for Children in London

The regulatory designations are based on data from the OTC-HOPE Phase 1/2 study, in which the first infant received ECUR-506 at the lowest dose level of 1.3 × 10¹³ genome copies per kilogram. This participant, who had experienced two hyperammonemic crises before treatment at 6.5 months of age, achieved complete discontinuation of ammonia scavenger medications by 12 weeks post-dosing, followed by normalisation of protein intake to age-appropriate levels. The treatment was generally well tolerated, though asymptomatic elevation of liver enzymes occurred at four weeks post-infusion – a pattern not uncommon in AAV-mediated gene therapy trials. Liver biopsy confirmed an acute T-cell inflammatory response, which resolved within four weeks with immunosuppressive therapy. From three to six months post-treatment, the infant maintained normal ammonia and glutamine levels without any hyperammonemic episodes.

»Our team is highly encouraged to see this baby, who after having experienced two spikes in blood ammonia levels before three and a half months of age, reach a point where he no longer needs ammonia scavengers and is eating age-appropriate levels of protein for a baby of his age,« said Julien Baruteau, principal investigator in the study and consultant in metabolic medicine at Great Ormond Street Hospital for Children in London. »This novel gene therapy approach might enable bypassing the need for liver transplantation.«

The RMAT programme, established under the 21st Century Cures Act, expedites the development and review of regenerative medicine therapies for serious or life-threatening diseases where early clinical evidence indicates potential to address unmet medical needs. ECUR-506 has also previously received Rare Pediatric Disease and Orphan Drug designations from the FDA. The OTC-HOPE study has regulatory authorisation in four geographies – the United States, United Kingdom, Spain, and Australia – with UCLA Mattel Children's Hospital and Children's Hospital of Colorado now open for enrollment, and additional Spanish sites in development. The trial is enrolling male infants up to seven months of age at screening who meet specific diagnostic criteria, with complete data readout anticipated in the first half of 2026.

The regulatory milestones were announced by iECURE earlier this month and by the UK Government in October 2025. Clinical data were presented in March 2025. Information about the OTC-HOPE study is available here.