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Effect of long-term sepiapterin treatment on dietary phenylalanine tolerance in patients with phenylketonuria: interim results from the phase 3 APHENITY Extension Study

Purpose - To report interim results from the ongoing, open-label, phase 3 APHENITY Extension Study (NCT05166161), evaluating long-term treatment with sepiapterin in patients with phenylketonuria. - Methods - Participants received an age-based dose of oral sepiapterin daily; those with mean blood phe...

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Main Authors: Spronsen, F. J. van (Author) , Peters, Heidi (Author) , Margvelashvili, Lali (Author) , Agladze, Dodo (Author) , Schwartz, Ida Vanessa D. (Author) , Giżewska, Maria (Author) , Hamazaki, Takashi (Author) , Guilder, Laura (Author) , MacDonald, Anita (Author) , Vijay, Suresh (Author) , Inwood, Anita (Author) , Minami, Maria (Author) , Fjellbirkeland, Olivia (Author) , Lund, Allan (Author) , Lah, Melissa (Author) , Thomas, Janet A. (Author) , Longo, Nicola (Author) , Kiykim, Ertuğrul (Author) , Ishige, Mika (Author) , Burlina, Alberto (Author) , Bélanger-Quintana, Amaya (Author) , Rutsch, Frank (Author) , Opladen, Thomas (Author) , Mungan, Halise (Author) , Ezgü, Fatih (Author) , Bratkovic, Drago (Author) , Chakrapani, Anupam (Author) , Ito, Tetsuya (Author) , Guimas, Arlindo (Author) , Zori, Roberto (Author) , Tchan, Michel (Author) , Sacharow, Stephanie (Author) , Oliveira, Anabela (Author) , Janeiro, Patricia (Author) , Guerra, Ixiu-Cabrales (Author) , Plana, Jaume Campistol (Author) , Yıldız, Yılmaz (Author) , Canda, Ebru (Author) , Khan, Aneal (Author) , Vockley, Jerry (Author) , Breilyn, Margo Sheck (Author) , Manti, Filippo (Author) , Larkin, Alex (Author) , Hughes, Catalina (Author) , Liu, Emelline (Author) , Gao, Lan (Author) , Ingalls, Kimberly (Author) , Smith, Neil (Author) , Muntau, Ania C. (Author)
Format: Article (Journal)
Language:English
Published: April 2026
In: Genetics in medicine
Year: 2026, Volume: 28, Issue: 4, Pages: 1-14
ISSN:1530-0366
DOI:10.1016/j.gim.2026.101683
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.gim.2026.101683
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S1098360026000018
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Author Notes:Francjan van Spronsen, Heidi Peters, Lali Margvelashvili, Dodo Agladze, Ida Vanessa D. Schwartz, Maria Giżewska, Takashi Hamazaki, Laura Guilder, Anita MacDonald, Suresh Vijay, Anita Inwood, Maria Minami, Olivia Fjellbirkeland, Allan Lund, Melissa Lah, Janet A. Thomas, Nicola Longo, Ertuğrul Kiykim, Mika Ishige, Alberto Burlina, Amaya Bélanger-Quintana, Frank Rutsch, Thomas Opladen, Halise Mungan, Fatih Ezgü, Drago Bratkovic, Anupam Chakrapani, Tetsuya Ito, Arlindo Guimas, Roberto Zori, Michel Tchan, Stephanie Sacharow, Anabela Oliveira, Patricia Janeiro, Ixiu-Cabrales Guerra, Jaume Campistol Plana, Yılmaz Yıldız, Ebru Canda, Aneal Khan, Jerry Vockley, Margo Sheck Breilyn, Filippo Manti, Alex Larkin, Catalina Hughes, Emelline Liu, Lan Gao, Kimberly Ingalls, Neil Smith, Ania C. Muntau
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Summary:Purpose - To report interim results from the ongoing, open-label, phase 3 APHENITY Extension Study (NCT05166161), evaluating long-term treatment with sepiapterin in patients with phenylketonuria. - Methods - Participants received an age-based dose of oral sepiapterin daily; those with mean blood phenylalanine (Phe) levels <360 μmol/L (<5.95 mg/dL) after 2 weeks underwent a 26-week dietary Phe tolerance assessment, wherein dietary Phe intake was adjusted and blood Phe levels monitored. Other participants continued treatment with optional diet liberalization. Primary endpoints included change from baseline to week 26 in dietary Phe intake and treatment-emergent adverse events (TEAEs). - Results - As of September 2, 2024, 169 participants received sepiapterin (median [minimum, maximum] age: 14.0 [0.2, 55.0] years, median exposure: 72.9 weeks); 102 participants underwent dietary Phe tolerance assessments. Mean (SD) dietary Phe intake increased from 27.6 (18.0) mg/kg/day at baseline to 62.5 (41.5) mg/kg/day at week 26 (least-squares mean change [SE]: 36.4 [2.8] mg/kg/day from baseline) (P < .0001 from post hoc analysis). The incidence of treatment-related TEAEs was 29.0%; 3 participants (1.8%) discontinued treatment owing to treatment-related TEAEs. There were no treatment-related serious TEAEs or deaths. - Conclusion - Interim results support the long-term safety of sepiapterin and demonstrate the potential for diet liberalization in adults and children with phenylketonuria. - ClinicalTrials.gov identifier - NCT05166161 (https://www.clinicaltrials.gov/study/NCT05166161; date of registration, December 8, 2021)
Item Description:Gesehen am 17.04.2026
Physical Description:Online Resource
ISSN:1530-0366
DOI:10.1016/j.gim.2026.101683

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