What Has Worked Well in Fabry Disease? An HTA Landscape Assessment Study
Author(s)
Raju Gautam, PhD1, Ratna Pandey, MSc2, Shilpi Swami, MSc1, Tushar Srivastava, MSc1.
1ConnectHEOR, London, United Kingdom, 2Connectheor, Delhi, India.
1ConnectHEOR, London, United Kingdom, 2Connectheor, Delhi, India.
OBJECTIVES: Fabry disease (FD) is a rare inherited lysosomal disorder impacting multiple organs such as kidneys, heart, skin and nervous system. Health technology assessments (HTAs) for rare diseases often face challenges of clinical uncertainty due to small patient numbers. This analysis aims to assess the HTA landscape of treatments for FD.
METHODS: Treatments available or approved for FD were identified by desk research. The submissions of these treatments were searched on following HTA websites: NICE (UK), SMC (Scotland), CDA (Canada), HAS (France), G-BA, IQWiG (Germany), and European Network of HTA (EUnetHTA). These submissions were assessed for the final recommendations for reimbursement and key issues.
RESULTS: We found four treatments for FD, including agalsidase alfa, agalsidase beta, pegunigalsidase alfa, and migalastat. Fourteen HTA reports of these treatments were identified between 2004 and March 2025., comprising 5 for CDA (two treatments had two reports each), 2 each for NICE, SMC, IQWiG, and 1 each for HAS, G-BA, and ACE (Singapore). Most assessments (7/14, 50%) received conditional recommendations, which include clinical (i.e., patients with amenable mutation, high clinical need, existing therapy not responsive) or commercial restrictions (i.e., commercial agreement, discount on patient access scheme). Three HTAs (21%) received full recommendations, while four (28%) were not recommended. The key issues highlighted that randomized controlled trials were limited by short duration, small sample sizes, and insufficiently robust comparative methodologies. While these treatments demonstrated effects on certain surrogate markers, their impact on clinically meaningful outcomes remains unclear.
CONCLUSIONS: This analysis suggests that HTA journey of treatments in FD has been challenging and inconsistent, with most HTA receiving conditional recommendations. While orphan medications address medical needs for a small number of patients and their development should be encouraged, HTA agencies mainly assess it from economic value in addition to the clinical benefits over the existing standard care.
METHODS: Treatments available or approved for FD were identified by desk research. The submissions of these treatments were searched on following HTA websites: NICE (UK), SMC (Scotland), CDA (Canada), HAS (France), G-BA, IQWiG (Germany), and European Network of HTA (EUnetHTA). These submissions were assessed for the final recommendations for reimbursement and key issues.
RESULTS: We found four treatments for FD, including agalsidase alfa, agalsidase beta, pegunigalsidase alfa, and migalastat. Fourteen HTA reports of these treatments were identified between 2004 and March 2025., comprising 5 for CDA (two treatments had two reports each), 2 each for NICE, SMC, IQWiG, and 1 each for HAS, G-BA, and ACE (Singapore). Most assessments (7/14, 50%) received conditional recommendations, which include clinical (i.e., patients with amenable mutation, high clinical need, existing therapy not responsive) or commercial restrictions (i.e., commercial agreement, discount on patient access scheme). Three HTAs (21%) received full recommendations, while four (28%) were not recommended. The key issues highlighted that randomized controlled trials were limited by short duration, small sample sizes, and insufficiently robust comparative methodologies. While these treatments demonstrated effects on certain surrogate markers, their impact on clinically meaningful outcomes remains unclear.
CONCLUSIONS: This analysis suggests that HTA journey of treatments in FD has been challenging and inconsistent, with most HTA receiving conditional recommendations. While orphan medications address medical needs for a small number of patients and their development should be encouraged, HTA agencies mainly assess it from economic value in addition to the clinical benefits over the existing standard care.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
HTA364
Topic
Health Technology Assessment, Study Approaches
Topic Subcategory
Decision & Deliberative Processes
Disease
Rare & Orphan Diseases