Gene therapy fast-tracked for liver disorder in babies

A novel gene insertion therapy to treat a rare liver disorder in newborns has received regulatory designations in the USA and the UK.

The therapy, ECUR-506, is currently in clinical development for the treatment of ornithine transcarbamylase (OTC) deficiency, a rare, X-linked genetic condition. OTC deficiency is a metabolic disorder characterised by a buildup of toxic ammonia in the blood, potentially leading to permanent brain damage if left untreated. The US Regenerative Medicine Advanced Therapy (RMAT) designation and the UK Innovative Licensing and Access Pathway (ILAP) provide structured regulatory support and access to faster approval routes, supporting the development of the therapy and the potential for earlier patient access.

'RMAT designation represents an important validation of ECUR-506 and the clinical data generated to date in neonatal onset OTC deficiency,' said Joseph Truitt, CEO of the Philadelphia-based biotechnology company iECURE, who developed the therapy. 'Together with the Innovation Passport granted under the UK's ILAP, these advancements reinforce our commitment to moving as efficiently as possible toward delivering a potentially durable therapeutic option for infants and families affected by this devastating disease.'

RMAT is a Food and Drug Administration designation that accelerates the development and review of regenerative therapies, including cell and gene therapies. ILAP is a UK-wide pathway that supports accelerated approval and early patient access to innovative medicines and technologies.

ECUR-506 is currently being investigated in the OTC-HOPE clinical trial, which is a first-in-human, phase 1/2, multi-centre trial. The trial is open for male infants under seven months of age who have a genetically confirmed neonatal onset OTC deficiency, with the aim of assessing the safety and efficacy of ECUR-506 as a viable treatment option. Targeting the underlying genetic cause has potential to offer more stable ammonia control and improve long-term patient outcomes.

ECUR-506 is designed as a one-time treatment to permanently insert a functional OTC gene. Preliminary findings of the therapy were reported last year, showing a complete clinical response in the first infant with neonatal OTC deficiency to receive the treatment (see BioNews 1272). Together, the RMAT and ILAP designations recognise ECUR-506 as a therapy under development for a condition with an unmet need, for which liver transplantation is currently the only cure.

'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 Dr 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'.

Dr Baruteau discussed the OTC-HOPE trial at a PET (Progress Educational Trust) event last year (see BioNews 1315 and 1319). Participant screening is underway in the UK, USA, Spain and Australia, with complete data expected during the first half of 2026.