Investigating the Patient-Relevance of Achieving Blood Phe Thresholds in PKU: Results From an Analysis of the OPAL Study
Author(s)
Milad Karimi, PhD1, Daniel Serrano, PhD2, Dammie Brown, MD3, Paul Okhuoya, MSc1.
1BioMarin Europe Ltd., London, United Kingdom, 2The Psychometrics Team, Ltd., London, United Kingdom, 3BioMarin Pharmaceutical Inc., Novato, CA, USA.
1BioMarin Europe Ltd., London, United Kingdom, 2The Psychometrics Team, Ltd., London, United Kingdom, 3BioMarin Pharmaceutical Inc., Novato, CA, USA.
OBJECTIVES: Phenylketonuria (PKU) is characterized by chronic elevations of blood phenylalanine (Phe). Untreated PKU patients can have Phe levels >1200 µmol/L, while the normal physiologic upper limit is ~120 µmol/L. The objective was to investigate the patient relevance of blood Phe reductions by exploring the association between Phe and patient-reported outcomes (PRO) in PKU.
METHODS: A secondary analysis was conducted using an interim data cut (March 2024) of OPAL, a phase 4, multicenter, observational study assessing the real-world safety and effectiveness of pegvaliase. Blood Phe monitoring was recommended monthly (collected per local standard of care), and PRO data were collected at baseline, 24-, 48-, and 96-weeks post-baseline. The PKU Symptom Severity and Impacts Scale (PKU-SSIS; psychometric validation ongoing) is a PKU-specific PRO employing a 7-day recall period. PKU-SSIS total score ranges from 0 to 100; higher scores indicate greater severity. Blood Phe measures within the recall period of PRO collection were averaged. Phe threshold achievement was operationalized as a count of the number of study visits at which blood Phe was <120 µmol/L. A linear mixed model was used to predict PKU-SSIS total scores from Phe<120 µmol/L, study visit, their interaction, and correlated random effects for subject and study visit.
RESULTS: Data from 48 patients were included at baseline. The Phe<120 µmol/L by study visit interaction was significant (p < 0.05), indicating that those who achieved the Phe threshold experienced more improvement in PKU-SSIS total score compared to those who did not. The marginal means and 95% confidence intervals estimated for changes from baseline to week 96 were -4 (-8.7, 0.69), -11 (-15.0, -6.5), and -18 (-26.0, -9.6) points for those experiencing 0, 1, or 2 visits of Phe<120 µmol/L.
CONCLUSIONS: Achievement of the <120 µmol/L Phe threshold was associated with improvements in health-related quality of life, suggesting that Phe threshold achievement is patient-relevant.
METHODS: A secondary analysis was conducted using an interim data cut (March 2024) of OPAL, a phase 4, multicenter, observational study assessing the real-world safety and effectiveness of pegvaliase. Blood Phe monitoring was recommended monthly (collected per local standard of care), and PRO data were collected at baseline, 24-, 48-, and 96-weeks post-baseline. The PKU Symptom Severity and Impacts Scale (PKU-SSIS; psychometric validation ongoing) is a PKU-specific PRO employing a 7-day recall period. PKU-SSIS total score ranges from 0 to 100; higher scores indicate greater severity. Blood Phe measures within the recall period of PRO collection were averaged. Phe threshold achievement was operationalized as a count of the number of study visits at which blood Phe was <120 µmol/L. A linear mixed model was used to predict PKU-SSIS total scores from Phe<120 µmol/L, study visit, their interaction, and correlated random effects for subject and study visit.
RESULTS: Data from 48 patients were included at baseline. The Phe<120 µmol/L by study visit interaction was significant (p < 0.05), indicating that those who achieved the Phe threshold experienced more improvement in PKU-SSIS total score compared to those who did not. The marginal means and 95% confidence intervals estimated for changes from baseline to week 96 were -4 (-8.7, 0.69), -11 (-15.0, -6.5), and -18 (-26.0, -9.6) points for those experiencing 0, 1, or 2 visits of Phe<120 µmol/L.
CONCLUSIONS: Achievement of the <120 µmol/L Phe threshold was associated with improvements in health-related quality of life, suggesting that Phe threshold achievement is patient-relevant.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO157
Topic
Clinical Outcomes, Patient-Centered Research
Topic Subcategory
Clinical Outcomes Assessment
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, Rare & Orphan Diseases