In 2012, the FDA established its Rare Pediatric Disease designation initiative through the Food and Drug Administration Safety and Innovation Act. Rare Pediatric Disease designation is granted to drugs or biologics intended to treat, diagnose, or prevent rare diseases affecting children (under age 18). Rare conditions are those affecting fewer than 200,000 children within the US. Alongside this status, a drug sponsor may be eligible for a Rare Pediatric Disease Priority Review Voucher, which can later be used to receive Priority Review on another marketing application. According to a news release from gene editing company iECURE, its therapy GTP-506 recently received Rare Pediatric Disease designation for the treatment of Ornithine Transcarbamylase (OTC) deficiency. 

GTP-506 utilizes adeno-associated virus (AAV) capsids with different viral payloads. It uses two vectors – an ARCUS nuclease vector, licensed from Precision BioSciences, and a therapeutic donor vector which helps insert a functional OTC gene into the patient. While still in preclinical studies, iECURE believes that GTP-506 has the potential to provide improved and restored metabolic function in those with OTC deficiency, filling a huge unmet need within this patient community.

Moving forward, the company plans to submit an Investigational New Drug (IND) application sometime in 2023. If accepted, the company would then move forward with human clinical trials to evaluate the safety, efficacy, and tolerability of this gene therapy solution. 

What is Ornithine Transcarbamylase (OTC) Deficiency?

OTC gene mutations cause Ornithine Transcarbamylase (OTC) deficiency, a rare genetic metabolic disorder characterized by high levels of ammonia in the blood. Normally, OTC is responsible for the production of the enzyme ornithine transcarbamylase. This plays a role in the urea cycle. However, these gene mutations prevent this cycle from running smoothly, causing ammonia to build up. When ammonia levels become too high, serious health consequences – including neurological damage, liver damage, and coma – can occur. Because OTC deficiency is an X-linked disorder, it affects males more than females. While females can show symptoms, these are typically less severe. 

There are multiple forms of OTC deficiency, depending on when symptoms appear. Neonatal-onset OTC deficiency typically manifests soon after birth. This form tends to be very severe. Without treatment, this form can be fatal. Symptoms can, but do not always, include:

• Hypotonia (weak/poor muscle tone)
• Lethargy
• Irritability
• Vomiting
• Poor feeding
• Failure to thrive
• Respiratory abnormalities
• Enlarged liver
• Developmental and intellectual delays
• Seizures

Alternately, the late-onset form typically appears in adolescence or adulthood, and is less severe. Symptoms may occur in episodes, often following another illness. These symptoms can, but do not always, include:

• Irritability
• Nausea and vomiting
• Hyperactivity or lethargy
• Self-mutilating behaviors
• Confusion
• Ataxia (impaired balance and coordination)