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Ornithine Transcarbamylase Gene Editing Program Nabs Another FDA Designation

iECURE is planning to submit an IND for GTP-506 in mid-2023.

The FDA has granted orphan drug designation to iECURE’s gene editing therapy GTP-506 for the potential treatment of ornithine transcarbamylase (OTC) deficiency.1

The announcement comes shortly after the FDA granted rare pediatric disease designation to GTP-206 in late August for the same indication.2 OTC deficiency is a rare genetic urea cycle disorder that can lead to irreversible neurological impairment, seizures, coma and death in children. iECURE plans to submit an investigational new drug application (IND) for GTP-506 to treat OTC deficiency in mid-2023.

“FDA’s decision to grant both orphan drug designation and rare pediatric disease designation for our investigational gene editing therapy aligns with our mission to provide treatments for patients where few if any options exist and highlights the urgency of developing a treatment for pediatric patients with OTC deficiency, a serious and life-threatening liver disease,” Joe Truitt, chief executive officer, iECURE, said in a statement.1 “We look forward to filing an IND application with the FDA for our first-in-human clinical trial next year.”

The in-vivo, gene insertion therapy GTP-506 uses twin adeno-associated virus capsids, an ARCUS nuclease AAV vector (GTP-506A) that targets gene editing in the PCSK9 gen locus and a therapeutic donor vector (GTP-506D) that inserts the correct OTC gene at the cut in the PCSK9 site. It is designed to restore metabolic function in patients with OTC deficiency.

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iECURE is collaborating on the GTP-506 program with the University of Pennsylvania’s Gene Therapy Program led by James M. Wilson, MD, PhD.2 With the help of the program’s translational expertise and infrastructure, thecompany has developed multiple potential product candidates, including programs in Citrullinemia Type 1 and phenylketonuria in addition to GTP-506.

Another of iECURE’s genome-editing programs, in hypercholesterolemia, is being developed in collaboration with Precision Biosciences, the company that also developed the ARCUS nuclease used in many of iECURE’s programs.

“OTC deficiency is a devastating genetic disease that presents as early as the first few days of life with loss of OTC enzyme activity. Current treatment options involve life-long dietary restrictions, nitrogen scavenger therapy, as well as liver transplant for patients who qualify,” George Diaz, MD, PhD, vice president, Urea Cycle Disorders,iECURE, added to the statement.1 “Targeted genome editing using GTP-506 has the potential to enable OTC-deficient patients to produce healthy, functional OTC enzyme in their own liver cells.”

GTP-506 previously showed positive preclinical data presented at the American Society of Gene & Cell Therapy (ASGCT) annual meeting in May 2022.3 Investigators assessed 2 different therapeutic genes for insertion and found that gene insertion was highly efficient and well-tolerated in nonhuman primates and long-term expression was 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.

REFERENCES
1. iECURE receives FDA orphan drug designation for GTP-506, an investigational gene editing product candidate for the treatment of ornithine transcarbamylase (OTC) Deficiency. News release. IECURE.
2. 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
3. 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/