RARE Daily

FDA Grants Fast Track Designation to Iecure for Treatment of Neonatal OTC Deficiency

May 7, 2024

Rare Daily Staff

The U.S. Food and Drug Administration granted Fast Track Designation to Iecure ECUR-506, the company’s in vivo gene insertion program designed to treat neonatal onset Ornithine Transcarbamylase deficiency.

“Receipt of Fast Track designation from the FDA is a validation of the severe unmet need for patients with neonatal onset OTC deficiency and a testament to the preclinical data generated to date for ECUR-506,” said Joe Truitt, CEO of Iecure. “The benefits of Fast Track designation may accelerate our ability to get ECUR-506 into physicians’ hands, which is incredibly important when every second counts for these babies.”

Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle disorder, an inherited metabolic condition caused by a genetic defect in a liver enzyme responsible for detoxification of ammonia. Individuals with OTC deficiency can build-up excessive levels of ammonia in their blood, potentially resulting in devastating consequences, including cumulative and irreversible neurological damage, coma, and death. The severe form of the condition emerges shortly after birth and is more common in boys than girls. The only treatment for early onset severe OTC deficiency is a liver transplant. Currently available medical therapies do not correct the disease and do not eliminate the risk of life-threatening symptoms or crises.

Iecure’s approach to gene editing for its initial programs, including OTC deficiency, relies on the delivery of two adeno-associated virus (AAV) capsids, each carrying different payloads. ECUR-506 comprises two vectors, an ARCUS nuclease vector targeting gene editing in the well-characterized PCSK9 gene locus and a donor vector that inserts the desired functional OTC gene. Iecure licensed the ARCUS nuclease for ECUR-506 from Precision BioSciences. The cut in the PCSK9 site serves as the insertion site for the OTC gene, providing a potential path to permanent expression of a healthy gene. ECUR-506 is being studied in the OTC-HOPE study, the first clinical meganuclease-based in vivo gene insertion program. The ECUR-506 program is the first in vivo gene insertion program to be cleared in the U.S. for study in infants, and it represents the first time that the ARCUS nuclease has been used to provide an in vivo insertion point for a functional gene in the clinic.

ECUR-506 previously received Rare Pediatric Disease and Orphan Drug designations from the FDA, and Orphan designation from the European Commission for the treatment of OTC deficiency.

iECURE’s OTC-HOPE study, a phase 1/2 first-in-human study in newborn males with genetically confirmed neonatal onset OTC deficiency, is open for enrollment at the Great Ormond Street Hospital for Children in the United Kingdom. In addition, trial sites in the United States and Australia are activating and will be enrolling later this year. The study is designed primarily to assess the safety and tolerability of ECUR-506 following intravenous administration of a single dose. Secondary objectives are to assess the pharmacokinetics and efficacy of ECUR-506. In addition, exploratory endpoints will assess disease-specific biologic markers, developmental milestones and quality of life.

The Fast Track designation is designed to facilitate the development and expedite the review of therapeutics to treat serious conditions that fill an unmet medical need. Therapeutics that receive Fast Track designation are eligible for more frequent meetings with and written communication from FDA to discuss the therapeutic’s development plan and ensure collection of appropriate data to support potential approval of the therapeutic. Provided relevant criteria are met, programs with Fast Track designation are also eligible for accelerated approval and priority review.

Photo: Joe Truitt, CEO of Iecure

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