FDA Recognizes Ornithine Transcarbamylase Deficiency Gene Editing Therapy


iECURE and the University of Pennsylvania Gene Therapy Program have collaborated to develop the GTP-506 program.

The FDA has granted rare pediatric disease designation to iECURE’s gene editing therapy GTP-506 being investigated for the potential treatment of Ornithine Transcarbamylase (OTC) deficiency.1

iECURE plans to submit an investigational new drug application (IND) for GTP-506 in mid-2023. OTC deficiency is a rare genetic urea cycle disorder that can lead to irreversible neurological impairment, seizures, coma and death in children.

“Receiving Rare Pediatric Disease Designation for GTP-506 for the treatment of OTC deficiency highlights the dire need for new treatment options for this devastating pediatric disease,” Joe Truitt, chief executive officer,iECURE, said in a statement.1 “GTP-506 is a potentially transformative therapy for babies born with OTC deficiency, and we expect to file an IND application with the FDA for our first-in-human clinical trial in mid-2023.”

GTP-506 is an in-vivo gene insertion therapy designed to restore metabolic function in patients with OTC deficiency. The therapy uses both an ARCUS nuclease adeno associated virus vector (AAV; GTP-506A) to target gene editing in the PCSK9 gene locus as well as a therapeutic donor vector (GTP-506D) that inserts the correct OTC gene at the cut in the PCSK9 site.

READ MORE: Homology Trades in Gene Delivery for Gene Editing to Treat Phenylketonuria

The GTP-506 program, along with others of iECURE’s programs, is being developed in collaboration with the University of Pennsylvania’s Gene Therapy Program led by James M. Wilson, MD, PhD. iECURE, with the help of UPenn’s translational expertise and infrastructure, has generated an initial pipeline of potential product candidates, including programs in Citrullinemia Type 1 and phenylketonuria in addition to GTP-506. iECURE is also partnered with Precision Biosciences for a genome-editing program in familial hypercholesterolemia. The ARCUS nuclease used in many of iECURE’s programs was also developed by Precision Biosciences.

iECURE previously presented positive preclinical data on GTP-506 at the American Society of Gene & Cell Therapy (ASGCT) annual meeting in May 2022.2 The data showed that in nonhuman primates, gene insertion was highly efficient and well-tolerated. Two different therapeutic genes were inserted, 1 for factor IX and 1 for OTC. Long-term gene expression data demonstrated 30-60% of normal levels of human FIX expression in newborn and 3-month olds for 17 to 20 months. The gene editing was well tolerated based on weight gain and alanine transaminase levels.

“One of the greatest challenges for using healthy genes to treat liver disorders affecting infants is the rapid division of liver cells, which prevents long-term expression of genes that have not integrated into the genome,” James M. Wilson, MD, PhD, Rose H. Weiss professor and director, Orphan Disease Center; professor, Departments of Medicine and Pediatrics, Perelman School of Medicine, and director, Gene Therapy Program, University of Pennsylvania, said in a previous statement.2 “The data we generated show exceptional promise for long-term expression of therapeutic genes, which we believe could help address the unmet medical needs for children with a range of inborn errors of metabolism, many of which result in death at a far too early age.” 

1. iECURE receives FDA Rare Pediatric Disease designation for GTP-506, an investigational gene editing product candidate for the treatment of ornithine transcarbamylase (OTC) deficiency. News release. IECURE. August 23, 2022. https://www.businesswire.com/news/home/20220823005280/en/iECURE-Receives-FDA-Rare-Pediatric-Disease-Designation-for-GTP-506-an-Investigational-Gene-Editing-Product-Candidate-for-the-Treatment-of-Ornithine-Transcarbamylase-OTC-Deficiency
2. Nonhuman primate data from iECURE’s knock-in in vivo gene editing approach for deadly urea cycle disorder to be presented in presidential symposium at ASGCT 2022. News release. iECURE. May 18, 2022. https://iecure.com/news/nonhuman-primate-data-from-iecures-knock-in-in-vivo-gene-editing-approach-for-deadly-urea-cycle-disorder-to-be-presented-in-presidential-symposium-at-asgct-2022/
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