Cost-Utility Analysis (CUA) of Sepiapterin for Treatment of Phenylketonuria (PKU)
Author(s)
Rongrong Zhang, MSc1, Anupam Chakrapani, MD2, Takashi Hamazaki, MD3, Melissa D. Lah, MD4, Ania C Muntau, MD5, Danielle J Ruebel, RDN4, Suresh Vijay, MD6, Roberto T Zori, MD7, Francois Feillet, MD8, Thomas OConnell, MA9, Jonathan J. Woolley, MSc9, Yixi Teng, MS9, Marjorie Crowell, MPA9, Ioannis Tomazos, MBA, PhD10.
1PTC Therapeutics, Askim, Sweden, 2Great Ormond Street Hospital for Children, London, United Kingdom, 3Department of Pediatrics, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan, 4Indiana University School of Medicine, Indianapolis, IN, USA, 5University Children’s Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, 6Birmingham Children's Hospital, Birmingham, United Kingdom, 7Pediatric Genetics and Metabolism, University of Florida, Gainesville, FL, USA, 8Reference Centre for Inborn Errors of Metabolism, Department of Pediatrics, Children's Hospital of Nancy, France, Nancy, France, 9Medicus Economics, Boston, MA, USA, 10Executive Director, Head of GHEOR, PTC Therapeutics, Warren, NJ, USA.
1PTC Therapeutics, Askim, Sweden, 2Great Ormond Street Hospital for Children, London, United Kingdom, 3Department of Pediatrics, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan, 4Indiana University School of Medicine, Indianapolis, IN, USA, 5University Children’s Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, 6Birmingham Children's Hospital, Birmingham, United Kingdom, 7Pediatric Genetics and Metabolism, University of Florida, Gainesville, FL, USA, 8Reference Centre for Inborn Errors of Metabolism, Department of Pediatrics, Children's Hospital of Nancy, France, Nancy, France, 9Medicus Economics, Boston, MA, USA, 10Executive Director, Head of GHEOR, PTC Therapeutics, Warren, NJ, USA.
OBJECTIVES: PKU results from an inborn deficiency in the phenylalanine (Phe) hydroxylase gene, causing reduced processing of Phe, an amino acid contained in dietary protein. A lifelong protein-restricted diet (PRD) is essential to prevent neurotoxic blood Phe levels. The pharmacological therapies sapropterin dihydrochloride and pegvaliase have received approvals for PKU. CUAs for these treatments have used inconsistent approaches, reflecting a lack of consensus on clinically-accurate modeling approaches. Here, a de-novo CUA model was developed to compare quality-adjusted life years (QALYs) for sepiapterin, a PKU treatment currently in development, vs. sapropterin and PRD, from a US societal perspective.
METHODS: A targeted review of sapropterin and pegvaliase health technology assessments was conducted to characterize challenges with the approaches for CUAs in PKU. These informed a scoping survey with clinical experts (n=8) to determine the clinical outcomes of greatest importance to model; subsequently, an international Delphi panel (n=11) identified clinically-accurate modelling approaches for these outcomes. A second clinician survey (n=29) was conducted to elicit perspectives on the associations of PKU with comorbidities and related mechanisms.
RESULTS: The de-novo economic model for PKU includes five health states defined by blood Phe levels. Clinical outcomes comprise four classes: symptoms/manifestations, intellectual disability, comorbidities, and diet restrictions/liberalization. Change in blood Phe and dietary tolerance are informed by clinical trials, and comorbidity burden by the clinician survey and literature. Comparative effectiveness of each treatment arm is specified based on the distribution of the cohort across blood Phe levels and dietary restrictions (total daily protein-equivalent consumption, and percentage from supplemental/Phe-free foods), which influence the four classes of clinical outcomes modeled.
CONCLUSIONS: This CUA model reflects a clinically-accurate approach for evaluating the benefits of sepiapterin compared to sapropterin or PRD for the treatment of PKU. The approach takes into account the heterogeneity in unmet need among individuals with PKU when evaluating relative treatment benefits.
METHODS: A targeted review of sapropterin and pegvaliase health technology assessments was conducted to characterize challenges with the approaches for CUAs in PKU. These informed a scoping survey with clinical experts (n=8) to determine the clinical outcomes of greatest importance to model; subsequently, an international Delphi panel (n=11) identified clinically-accurate modelling approaches for these outcomes. A second clinician survey (n=29) was conducted to elicit perspectives on the associations of PKU with comorbidities and related mechanisms.
RESULTS: The de-novo economic model for PKU includes five health states defined by blood Phe levels. Clinical outcomes comprise four classes: symptoms/manifestations, intellectual disability, comorbidities, and diet restrictions/liberalization. Change in blood Phe and dietary tolerance are informed by clinical trials, and comorbidity burden by the clinician survey and literature. Comparative effectiveness of each treatment arm is specified based on the distribution of the cohort across blood Phe levels and dietary restrictions (total daily protein-equivalent consumption, and percentage from supplemental/Phe-free foods), which influence the four classes of clinical outcomes modeled.
CONCLUSIONS: This CUA model reflects a clinically-accurate approach for evaluating the benefits of sepiapterin compared to sapropterin or PRD for the treatment of PKU. The approach takes into account the heterogeneity in unmet need among individuals with PKU when evaluating relative treatment benefits.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
EE295
Topic
Economic Evaluation
Disease
Rare & Orphan Diseases