| Title: | Efficacy and safety of sepiapterin versus sapropterin in patients with phenylketonuria : results from the Phase 3, randomized, crossover, open-label, active-controlled AMPLIPHY trial |
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| Authors: | ID Giżewska, Maria (Author)
ID Inwood, Anita (Author)
ID Tyčová, Renáta (Author)
ID Vijay, Suresh (Author)
ID Fjellbirkeland, Olivia (Author)
ID Grošelj, Urh (Author), et al. |
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| Files: |  PDF - Presentation file, download (1,25 MB)
MD5: 8FD0CABD7704820A090B35DC1722B120
 URL - Source URL, visit https://www.metabolismjournal.com/article/S0026-0495(26)00022-3/fulltext
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| Language: | English |
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| Typology: | 1.01 - Original Scientific Article |
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| Organization: |  UKC LJ - Ljubljana University Medical Centre
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| Abstract: | Aim: AMPLIPHY is the first Phase 3 study comparing sepiapterin versus sapropterin in children and adults with phenylketonuria (PKU). Methods: AMPLIPHY was an international, Phase 3, two-part, open-label study in participants with PKU aged ≥2 years. Participants responsive to sepiapterin (60 mg/kg/day) in Part 1 (≥20% reduction in blood phenylalanine [Phe]) entered Part 2, a crossover treatment period, and were randomized 1:1 to alternative treatment sequences of sepiapterin (60 mg/kg/day, licensed dosage) and sapropterin (20 mg/kg/day, maximum licensed dosage) for 4 weeks each, with a 14-day washout between treatments. The primary endpoint was mean change in blood Phe from baseline to Weeks 3-4 of each treatment period (Part 2). Results: Of 82 participants enrolled, 67 (81.7%) and 62 (75.6%) had reductions in blood Phe ≥20% and ≥ 30%, respectively, in Part 1. Sixty-two participants were randomized in Part 2 (mean [SD] age, 15.8 [10.8] years). In the primary analysis set (≥30% reduction in blood Phe in Part 1, n = 58), mean (SD) baseline blood Phe before sepiapterin and sapropterin treatment was 725.8 (302.1) and 790.4 (370.0) μmol/L, respectively. Least-squares mean (SE) reduction in blood Phe from baseline was -437.0 (28.0) and - 256.6 (28.2) μmol/L, respectively, representing a least-squares mean difference of -180.4 μmol/L (95% CI: -229.5, -131.4; p < 0.0001) and a relative 70% greater reduction with sepiapterin versus sapropterin. Both treatments were well tolerated, with safety profiles consistent with previous reports. Conclusions: Sepiapterin was superior to the highest approved dose of sapropterin in lowering blood Phe. No new safety signals were observed. |
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| Keywords: | AMPLIPHY, efficacy, PKU, phenylketonuria, phenylalanine, safety, sapropterin, sepiapterin |
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| Publication status: | Published |
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| Publication version: | Version of Record |
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| Year of publishing: | 2026 |
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| Number of pages: | str. 1-10 |
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| Numbering: | Vol. 178, [article no.] 156513 |
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| PID: | 20.500.12556/DiRROS-28316  |
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| UDC: | 616 |
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| ISSN on article: | 1532-8600 |
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| DOI: | 10.1016/j.metabol.2026.156513 |
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| COBISS.SI-ID: | 267796995 |
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| Note: | Nasl. z nasl. zaslona;
Opis z dne 9. 2. 2026;
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| Publication date in DiRROS: | 13.03.2026 |
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| Views: | 17 |
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| Downloads: | 13 |
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