Clear route to registration positions lucerastat as the potential first oral therapy for all patients with Fabry disease

Core Insights - Idorsia Ltd has announced the design of its FDA-agreed Phase 3 registration program for lucerastat in treating Fabry disease, focusing on its impact on renal pathology to secure market authorization [1][4] - The Fabry disease market is projected to reach around USD 4 billion by 2034, indicating a growing demand for innovative therapies [2] - Lucerastat is positioned as a differentiated oral therapy that addresses the underlying biology of Fabry disease, with a mutation-independent mechanism and long-term evidence supporting its efficacy [3][21] Company Developments - The registration program includes two clinical trials aimed at characterizing lucerastat's renal effects, aligning with feedback from health authorities [4] - A pivotal kidney biopsy study and a renal function comparative study are part of the program, with a potential regulatory filing expected as early as 2029 [5][6] - Long-term data from the MODIFY study indicates that lucerastat treatment is associated with a slower decline in kidney function compared to historical data [11] Clinical Findings - The MODIFY study did not meet its primary endpoint of reducing neuropathic pain, but showed significant reductions in plasma and urinary Gb3 levels, indicating robust pharmacodynamic effects [10][21] - An interim analysis revealed a notable reduction in the rate of eGFR decline in patients treated with lucerastat, particularly in those with severe disease [11] - Kidney biopsy results from long-term treated patients demonstrated low-to-no levels of kidney Gb3 inclusions, supporting the drug's efficacy [12] Market Context - Fabry disease is a rare disorder with approximately 16,000 diagnosed patients in major markets, expected to increase to around 21,000 by 2034 [2] - Current treatment options have limitations, creating a significant unmet need for a well-tolerated, oral, disease-modifying therapy [17] - Lucerastat's mechanism of action allows it to be effective regardless of α-Gal A activity or prior treatment history, broadening therapeutic options for patients [18][21]