Idorsia starts Phase 3 kidney study for lucerastat in Fabry disease

Idorsia has initiated FAB-KLEAR, a pivotal Phase 3 kidney biopsy study of its oral candidate lucerastat in adult patients with Fabry disease, while simultaneously announcing a co-development and commercialisation agreement with Japan-based Nxera Pharma. The Swiss biotech says both studies, taken together, are designed to support a regulatory filing as early as 2029.

Lucerastat is an investigational substrate reduction therapy that inhibits glucosylceramide synthase, thereby reducing the synthesis of globotriaosylceramide (Gb3), the lipid that accumulates in Fabry patients due to deficient alpha-galactosidase A activity. Unlike enzyme replacement therapies (ERTs) or chaperone treatments, lucerastat is designed to work regardless of GLA mutation type or prior therapy, positioning it as a potential option for patients who are poorly served by current standard of care.

The FAB-KLEAR study and deal terms

FAB-KLEAR is an open-label study enrolling 16 treatment-naive or pseudo-naive adult male patients. Its primary endpoint is the change from baseline to Month 18 in kidney Gb3 BLISS score, a quantitative measure of Gb3 inclusions in kidney peritubular capillaries. A companion 74-patient study, FAB-SWITCH, will compare lucerastat against standard-of-care ERTs and is intended to establish the drug as the first oral therapy addressing the full spectrum of Fabry patients. Idorsia says both programmes have been aligned with the US FDA, and the design is consistent with EMA feedback from prior interactions.

Under the Nxera agreement, which follows Nxera's exercise of a pre-existing option tied to the 2023 sale of Idorsia's Asia Pacific operations, Nxera will pay CHF 7 million upfront and contribute to the global Phase 3 programme. Nxera receives exclusive development and commercialisation rights for Japan and selected Asia Pacific territories excluding China; Idorsia retains royalty eligibility on net sales in those markets.

Roland Wandeler, chief executive of Idorsia, called Nxera's decision to exercise its option "a significant endorsement of both the programme and the opportunity to change the treatment paradigm for people living with Fabry disease."

Regulatory backdrop and market context

The rationale for FAB-KLEAR draws on data from the Phase 3 MODIFY study and its long-term open-label extension, published in Nature Communications in January 2026. MODIFY did not meet its primary endpoint of neuropathic pain reduction, an outcome Idorsia's chief medical officer Amer Joseph acknowledged is "proving difficult to reach in Fabry disease." Nevertheless, lucerastat produced sustained reductions in plasma and urinary Gb3 levels, and an interim OLE analysis covering patients with at least 42 months of treatment showed a meaningful attenuation of eGFR decline compared with each patient's pre-treatment trajectory (eGFR slope, historical: -3.50; lucerastat: -1.64). The effect was particularly pronounced in classic male patients and those with impaired renal function at baseline.

Fabry disease affects approximately 16,000 diagnosed patients across the seven major markets, according to market research cited in the release, a figure projected to reach around 21,000 by 2034, with the overall market valued at roughly USD 4 billion by that date. The condition remains chronically underdiagnosed given its variable presentation. Current approved options include ERTs such as agalsidase alfa and agalsidase beta, as well as the chaperone migalastat, which is effective only in patients with amenable mutations. An oral therapy with broad mutation independence would address a meaningful unmet need, particularly in patients who develop antibodies to ERT, a cohort in which lucerastat's renal data appear especially striking.

Lucerastat holds orphan drug designation in both the US and EU, which provides regulatory incentives including extended market exclusivity on approval. Idorsia, headquartered near Basel and listed on the SIX Swiss Exchange, will need to demonstrate histological improvement in the small FAB-KLEAR cohort to satisfy the FDA's requirements for a biopsy-based registration strategy. Investors should note that the pivotal readout is not expected before the mid-2020s and that a failed primary endpoint in MODIFY remains an overhang on sentiment toward the programme.