Slide 1: Final safety and efficacy of pegvaliase in Japanese adults with phenylketonuria
Final safety and efficacy of pegvaliase in Japanese adults with phenylketonuria Presented by: Y Nakajima Y Nakajima1, M Ishige2, T Ito1, T Hamazaki3, M Kuwahara4, L Lee5, H Shintaku3 Scan for a digital copy of this presentation 1Department of Pediatrics, Fujita Health University School of Medicine,
Slide 2: COI disclosure
日本先天代謝異常学会 ＣＯ Ｉ 開示 筆頭発表者名： 中島 葉子 Employees: M Kuwahara, L Lee Clinical trial investigators: Y Nakajima, M Ishige, T Ito, T Hamazaki, H Shintaku (BioMarin)
Slide 3: Background and study objective
• PKU is caused by deficiency of phenylalanine hydroxylase, leading to elevated Phe levels in the blood and brain, which negatively impacts neurocognitive function in adults with PKU1-3 • The Japanese clinical guidelines recommend maintaining blood Phe below 360 µmol/L4 • Alongside diet therapy, Bio
Slide 4: Study design
• The study included a low-dose induction period followed by sequential titration to a maintenance dose (see Figure) • During Part 1, participants were instructed to maintain a stable diet, assessed using data from 3-day diet diaries; however, diet modifications could be made if blood Phe levels wer
Slide 5: Participant baseline characteristics
Characteristic All participants* (N=12) • A total of 12 participants were Age, years enrolled into the study from Mean (SD) 29.4 (8.1) 3 clinical sites in Japan Sex, n (%) Female 4 (33.3) • Mean pegvaliase treatment Weight, kg duration was 166.4 weeks Mean (SD) 64.4 (15.2) (range: 24–212 weeks) Medi
Slide 6: Mean blood Phe over time
1200 Mean (SE) Blood Phe (μmol/L) 1000 800 600 600 μmol/L 400 360 μmol/L 200 0 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 128 136 144 152 160 168 176 184 192 200 208 n 11 11 11 10 11 11 11 11 11 11 11 10 9 10 10 10 10 10 9 10 10 9 10 10 10 7 5 Week • Blood Phe data are available for 208 weeks
Slide 7: Dietary protein intake over time
70 Intact food Mean (SE) Dietary Protein Intake (g) Medical food 60 50 40 30 20 10 0 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 128 136 144 152 160 168 176 184 192 200 208 Intact food, n 12 12 12 12 11 11 11 11 11 10 11 11 10 10 10 10 10 10 10 10 10 10 10 10 10 7 5 Medical food, n 12 12 12 12
Slide 8: Blood Phe, protein intake and pegvaliase exposure
2000 Protein (g)/Pegvaliase Exposure (mg) 150 Participant 11 Blood Phe (μmol/L) 140 1800 Protein (g) from medical formula 130 1600 Protein (g) from intact food 120 Pegvaliase exposure (mg) Blood Phe (μmol/L) 110 1400 100 1200 90 80 1000 70 800 60 50 600 40 400 30 20 200 10 0 0 0 8 16 24 32 40 48 56
Slide 9: Participant details and first achievement of Phe ≤360 µmol/L
Blood Phe First achievement Participant details (μmol/L) of ≤360 µmol/L Pegvaliase administration Protein intake Daily Time to At last exposure BL Last follow-up* Age Weight dose reach Duration Dose Total Medical Total Medical ID (years) Sex (kg) BL Final (mg) (weeks) (weeks) (mg) Frequency (g) food
Slide 10: Safety summary: adverse events
• All 12 participants (100%) experienced ≥1 treatment-emergent AE – The most common AEs were injection site erythema and injection site swelling (83.3% each), arthralgia (75.0%), malaise and nasopharyngitis (66.7% each), allergic dermatitis (58.3%), and injection site pruritus and urticaria (50.0% e
Slide 11: Conclusions
Administration of pegvaliase in Japanese adults with PKU with blood Phe concentrations >600 μmol/L effectively reduced blood Phe levels to within, and often below, guideline-recommended ranges Treatment was generally well tolerated with no new safety issues identified Hypersensitivity-related AEs we
Slide 12: Acknowledgments
• The authors would like to thank the study participants and their families for their contributions to this research • The authors acknowledge medical writing assistance provided by Jason Vuong, BPharm, CMPP, of ProScribe – Envision Pharma Group and funded by BioMarin Pharmaceutical Inc. Scan for a
Slide 13: Individual participant profiles: Participants 2 and 3
2000 2000 Protein (g)/Pegvaliase Exposure (mg) Protein (g)/Pegvaliase Exposure (mg) 150 150 Participant 2 Participant 3 140 140 1800 1800 130 130 1600 120 1600 120 Blood Phe (μmol/L) Blood Phe (μmol/L) 110 110 1400 1400 100 100 1200 90 1200 90 80 80 1000 1000 70 70 800 60 800 60 50 50 600 600 40 40
Slide 14: Participants 1, 2, 3
Participant 1 Participant 2 Participant 3 Participant 4 14 Phe, phenylalanine
Slide 15: Participants 5, 6, 7
Participant 5 Participant 6 Participant 7 Participant 8 15 Phe, phenylalanine
Slide 16: Participants 9, 12, 10
Participant 9 Participant 10 Participant 12 16 Phe, phenylalanine