Core Insights - Idorsia Ltd has published results from the pivotal Phase 3 MODIFY study and its open-label extension, highlighting the potential of lucerastat as an oral substrate reduction therapy for Fabry disease, particularly in patients with renal impairment [1][3]. Study Overview - The MODIFY study was a multicenter, double-blind, randomized, placebo-controlled trial involving 118 patients, aimed at assessing the efficacy and safety of lucerastat as an oral monotherapy for adult patients with Fabry disease [2]. - The study's primary endpoint of reducing neuropathic pain over six months was not met; however, lucerastat showed significant reductions in plasma and urinary Gb3 levels compared to placebo, with sustained effects observed in the open-label extension [3][17]. Renal Function Insights - An interim analysis of the open-label extension indicated a notable improvement in renal function trajectory, with a reduced rate of eGFR decline in patients treated with lucerastat compared to their eGFR slope prior to enrollment [4][9]. - In patients with impaired renal function or fast-deteriorating eGFR at baseline, lucerastat was associated with a significant reduction in kidney function loss, suggesting a potential disease-modifying effect [4][17]. Long-term Treatment and Tolerability - The open-label extension has collected data from patients treated with lucerastat for over 42 months, with some receiving treatment for more than 6 years, demonstrating good tolerability and no serious treatment-related adverse events [5][8]. - A kidney biopsy sub-study was conducted to evaluate Gb3 inclusions in kidney cells of male participants with classic Fabry disease treated for over 3 years with lucerastat [5]. Future Directions - The company is collaborating with the US FDA to design a new Phase 3 program to ensure a regulatory pathway for lucerastat's approval [6][10]. - A post-trial access program is being established to ensure continuity of care for participants still receiving lucerastat at the study's closure [7].

Core Insights - Idorsia Ltd has published results from the pivotal Phase 3 MODIFY study and its open-label extension, demonstrating the potential of lucerastat as an oral substrate reduction therapy for Fabry disease, particularly in patients with renal impairment [1][17]. Study Overview - The MODIFY study was a multicenter, double-blind, randomized, placebo-controlled trial involving 118 patients, aimed at assessing the efficacy and safety of lucerastat as an oral monotherapy for adult patients with Fabry disease [2]. - The study's primary endpoint of reducing neuropathic pain over six months was not met; however, lucerastat showed significant reductions in plasma and urinary Gb3 levels compared to placebo, with sustained effects observed in the open-label extension [3][17]. Renal Function Insights - An interim analysis of the open-label extension indicated a notable improvement in renal function trajectory, with a reduced rate of eGFR decline in patients treated with lucerastat compared to their eGFR slope prior to enrollment [4][9]. - In patients with impaired renal function or fast-deteriorating eGFR at baseline, lucerastat was associated with a significant reduction in kidney function loss, suggesting a potential disease-modifying effect [4][9]. Long-term Treatment and Tolerability - The open-label extension has collected data from patients treated with lucerastat for over 42 months, with some receiving treatment for more than 6 years, showing good tolerability and no serious treatment-related adverse events [5][8]. - A kidney biopsy sub-study was conducted to evaluate Gb3 inclusions in kidney cells of male participants with classic Fabry disease treated for over 3 years with lucerastat monotherapy [5]. Future Directions - The company is collaborating with the US FDA to design a new Phase 3 program to ensure a regulatory pathway for lucerastat's approval [6][10]. - A post-trial access program is being established to ensure continuity of care for participants still receiving lucerastat at the study's closure [7]. Industry Context - Fabry disease is a rare lysosomal storage disorder caused by mutations in the GLA gene, leading to the accumulation of Gb3 and resulting in progressive damage to multiple organ systems [10][11]. - Current treatment options are limited, highlighting the unmet need for a well-tolerated, oral, disease-modifying therapy that can be used regardless of genotype or prior treatment history [13][14].