20.500.12556/DiRROS-28316 Efficacy and safety of sepiapterin versus sapropterin in patients with phenylketonuria results from the Phase 3, randomized, crossover, open-label, active-controlled AMPLIPHY trial 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. AMPLIPHY efficacy PKU phenylketonuria phenylalanine safety sapropterin sepiapterin true false true Angleški jezik Ni določen Neznano 2026-03-13 14:10:08 2026-03-13 14:10:08 2026-03-14 04:26:02 0000-00-00 00:00:00 2026 0 0 Nasl. z nasl. zaslona; Opis z dne 9. 2. 2026; str. 1-10 [article no.] 156513 Vol. 178 2026 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616 1532-8600 10.1016/j.metabol.2026.156513 267796995 RAZ_Giżewska_Maria_2026.pdf RAZ_Giżewska_Maria_2026.pdf 1 8FD0CABD7704820A090B35DC1722B120 f01bdae7c5b6db91c83db0685422a94e1866c5a05671e7270f392491872df888 266d8679-1ede-11f1-acf8-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=41815 https://www.metabolismjournal.com/article/S0026-0495(26)00022-3/fulltext 0 34c48ce0-1ede-11f1-acf8-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=41816 Univerzitetni klinični center Ljubljana 0 0 0