P283: A prolonged-release formula has a positive impact on morning phenylalanine and tyrosine fluctuations in patients with classical phenylketonuria (PKU)

Results: A total of 137 participants are enrolled as of February 2024: 2E/R4, n=45; 2D/R3, n=49; and 2C/R5, n=43; age 4-7y, n=10; 8-16y, n=59; and 17y, n=68.79/137 (58.0%) are female and 75/137 (54.7%) are ambulatory (2E/R4, n=25; 2D/R3, n=36; and 2C/R5, n=14).At baseline, 26.7% (2E/R4), 2.0% (2D/ R3), and 16.3% (2C/R5) have cardiac disorders.Mean baseline NSAD total scores by subtype and age (4-7y, 8-16y, 17y) are (ambulatory) 2E/R4: 44.0, 40.6, 32.0; 2D/R3: 46.5, 34.3, 33.3; and 2C/R5: 47.0, 24.0, N/A; and (nonambulatory) 2E/R4: N/A, 1.5, 4.1; 2D/R3: N/A, 8.7, 1.5; and 2C/R5: N/A, 4.8, 2.5, respectively.Mean baseline PUL total scores by subtype and age (4-7y, 8-16y, 17y) are (ambulatory) 2E/R4: 36.8, 37.8, 36.6;2D/R3: 33.5, 36.0,34.3; and 2C/R5: 37.0, 30.3,N/A; and (nonambulatory) 2E/R4: N/A, 14.7, 16.9; 2D/R3: N/A, 29.3, 13.9; and 2C/R5: N/A, 17.1, 15.9, respectively.In ambulatory participants, physical functional assessments are generally worse in older patients across each subtype.Pulmonary functional assessments are generally worse in older nonambulatory patients (mean % forced expiratory volumes by subtype and age [4-7y, 8-16y, 17y] are 2E/R4: N/A, 75.86, 54.12; 2D/R3: N/A, 91.28, 56.71; and 2C/R5: N/A, 84.18, 55.72, respectively).Of the participants with ECG data available, 26.0% of ambulatory and 54.2% of nonambulatory participants have clinically insignificant ECG abnormalities; no ambulatory and 5.1% of nonambulatory participants have clinically significant ECG abnormalities.Conclusion: JOURNEY is a natural history study of LGMD, adding to the overall understanding of clinical characteristics and disease progression of individuals with subtypes 2E/R4, 2D/R3, and 2C/R5.Understanding of the clinical characteristics and disease progression of LGMD may aid physicians with diagnosis and development of appropriate therapies.