Effect of avalglucosidase alfa on disease-specific and general patient-reported outcomes in treatment-naïve adults with late-onset Pompe disease compared with alglucosidase alfa: Meaningful change analyses from the Phase 3 COMET trial.

BACKGROUND: The Phase 3 COMET trial (NCT02782741) comparing avalglucosidase alfa and alglucosidase alfa included health-related quality of life (HRQoL) assessments in treatment-naïve patients with late-onset Pompe disease (LOPD). Here, we further characterize results from disease-specific and general patient-reported outcome (PRO) measures. METHODS: Adults who participated in the COMET trial receiving avalglucosidase alfa or alglucosidase alfa (both 20 mg/kg biweekly) during the 49-week double-blind treatment period were included in the analysis. Proportions of patients exceeding meaningful change thresholds at Week 49 were compared post hoc between treatment groups. PROs and their meaningful change thresholds included: Pompe Disease Severity Scale (PDSS; decrease 1.0-1.5 points), Pompe Disease Impact Scale (PDIS; decrease 1.0-1.5 points), Rasch-built Pompe-specific Activity Scale (R-PAct; change from unable to able to complete activity), 12-item Short Form Health Survey (SF-12; physical component summary [PCS] score: increase ≥6 points, mental component summary [MCS] score: increase ≥7 points), EuroQol 5 Dimension 5 Level (EQ-5D-5L; improvement of ≥1 category), and Patient Global Impression of Change (PGIC; any improvement). RESULTS: The analysis included 99 adult patients (avalglucosidase alfa n = 50; alglucosidase alfa n = 49). Patients who received avalglucosidase alfa had significantly greater odds of achieving a meaningful change versus alglucosidase alfa for the PDSS Shortness of Breath (OR [95% CI] 11.79 [2.24; 62.18]), Fatigue/Pain (6.24 [1.20; 32.54]), Morning Headache (13.98 [1.71; 114.18]), and Overall Fatigue (5.88 [1.37; 25.11]) domains, and were significantly more likely to meet meaningful change thresholds across multiple PDSS domains (all nominal p < 0.05). A numerically greater proportion of patients in the avalglucosidase alfa group were able to complete selected activities of the R-PAct compared with the alglucosidase alfa group. Significantly greater proportions of patients who received avalglucosidase alfa achieved meaningful improvements for EQ-5D-5L usual activities dimension, EQ visual analog scale, and all four PGIC domains. The proportion of patients with improvements in SF-12 PCS and MCS was greater in the avalglucosidase alfa group versus alglucosidase alfa group, but was not significant (p > 0.05). CONCLUSIONS: These analyses show that avalglucosidase alfa improves multiple symptoms and aspects of daily functioning, including breathing and mobility. This supports the clinical relevance of the effects of avalglucosidase alfa on HRQoL for patients with LOPD.

Unveiling the untreated: development of a database algorithm to identify potential Fabry disease patients in Germany.

BACKGROUND: Fabry disease (FD), an X-linked lysosomal storage disorder, is caused by mutations in the gene encoding α-galactosidase A, resulting in lysosomal accumulation of globotriaosylceramide and other glycosphingolipids. Early detection of FD is challenging, accounting for delayed diagnosis and treatment initiation. This study aimed to develop an algorithm using a logistic regression model to facilitate early identification of patients based on ICD-10-GM coding using a German Sickness Fund Database. METHODS: The logistic regression model was fitted on a binary outcome variable based on either a treated FD cohort or a control cohort (without FD). Comorbidities specific to the involved organs were used as covariates to identify potential FD patients with ICD-10-GM E75.2 diagnosis but without any FD-specific medication. Specificity and sensitivity of the model were optimized to determine a likely threshold. The cut-point with the largest values for the Youden index and concordance probability method and the lowest value for closest to (0,1) was identified as 0.08 for each respective value. The sensitivity and specificity for this cut-point were 80.4% and 79.8%, respectively. Additionally, a sensitivity analysis of the potential FD patients with at least two codes of E75.2 diagnoses was performed. RESULTS: A total of 284 patients were identified in the potential FD cohort using the logistic regression model. Most potential FD patients were < 30 years old and female. The identification and incidence rates of FD in the potential FD cohort were markedly higher than those of the treated FD cohort. CONCLUSIONS: This model serves as a tool to identify potential FD patients using German insurance claims data.