LoargysArginase 1 deficiency
New molecular entity
Development and Regulatory status
Phase III Clinical Trials
Phase III Clinical Trials
Aug 22EMA validate MAA for treatment of Arginase 1 deficiency .
Jun 22The FDA have issued a refusal-to-file letter and has requested more data to support pegzilarginase´s efficacy. The company plan to meet with the FDA to address the letter .
Apr 22Immedica Pharma have submitted a Biologics License Application (BLA) to the US FDA for pegzilarginase for arginase 1 deficiency with a request for priority review. 
Dec 21Aeglea Bio plan to file for FDA approval in the first half of 2022 and to work with European partner Immedica Pharma to submit applications outside the US .
Jun 19Aeglea BioTherapeutics announces that the US FDA has granted a breakthrough therapy status for pegzilarginase for treatment of ARG1-D, based on data from the PI/II and ongoing PII open-label extension clinical trials .
Sep 18US FDA grants rare paediatric disease designation to pegzilarginase for the treatment of patients with arginase 1 deficiency. The designation confirms the eligibility to receive a Rare Pediatric Disease priority review voucher upon approval of a qualifying BLA for pegzilarginase if approved before October 1, 2026 .
May 16Granted fast track status in US .
Apr 16Has orphan drug status in US and EU .
Recombinant enzyme replacement derived from human arginase 1 and engineered to include the substitution of cobalt for the manganese cofactor and pegylated to increase catalytic activity and serum stability compared to native human arginase 1
ARG1-D has been estimated to occur in 1 in 300,000-1,000,000 births. It is among the least common of all the disorders of the urea cycle. The estimated frequency of urea cycle disorders collectively is one in 30,000. However, because urea cycle disorders like ARG1-D often go unrecognized, these disorders are under-diagnosed, making it difficult to determine the true frequency of urea cycle disorders in the general population . Company estimates there are 25 people with ARG1-D in the UK .
Arginase 1 deficiency
Trial or other data
Apr 22Further data from PIII double-blinded, placebo-controlled PEACE study (n=32 pts with ARG1-D aged 2 or under) shows 76.7% arginine reduction in pt plasma levels. Overall 90.5% in the treatment group reached normal plasma arginine levels. Pts were also reported to display improved Gross Motor Function Measure E and 2-minute walk test measurements. Adverse effects were mild to moderate and patient tolerability was high.
Dec 21PIII PEACE met primary endpoint of a statistically significant drop in plasma arginine from baseline after 24 weeks of treatment observed in 90.5% of pts given pegzilarginase. Company plans to submit biologics license application to the FDA in the first half of 2022. 
May 21PIII PEACE study continues but is no longer recruiting .
Apr 19PIII PEACE study to evaluate the safety and efficacy of pegzilarginase in patients with ARG1-D starts (NCT03921541). 32 subjects aged 2 years and older will be randomised to treatment following completion of all screening assessments and confirmation of study eligibility in a 2:1 ratio to receive weekly IV infusions of pegzilarginase plus individualized disease management (IDM) or placebo plus IDM during the 24-week double blind treatment period. After completion of the 24-week double-blind treatment period, each subject will enter the long term, open-label extension, the first 8 weeks of which are blinded. During the long-term extension, all subjects receive pegzilarginase plus IDM. After 8 weeks of the LTE study, patients have the option to receive treatment by subcutaneous administration (SC). Study sites include the US and Europe (including the UK). Primary outcome is change from baseline in plasma arginine concentration after 24 weeks of treatment; collection of these data is due to complete Sep 21 .
Feb 19PI/II study (NCT02488044) completes .
Jun 16PI/II study to evaluate the safety and tolerability of IV administration of AEB1102 for the treatment of pediatric and adult patients with arginase I deficiency and hyperargininemia starts (NCT02488044). This study will be conducted in 2 parts: Part 1 (Single Ascending Dose Escalation) and Part 2 (Repeated Dosing). Each part will be preceded by a baseline assessment of arginine levels. All patients who participate in Part 1 may continue AEB1102 dosing in Part 2 if they qualify for continued dosing. 16 patients aged from 2 years will be recruited in the US, Portugal and in the UK (at Great Ormond Street). AEB1102 will be administered, in Part 1, in up to 7 doses given up to every other week over a maximum of 14 weeks; and in Part 2 each patient will receive up to 8 weeks of repeat-dose therapy .