FAB-KLEAR investigates lucerastat as a potential disease-modifying therapy targeting the kidney manifestations of Fabry disease.

Nxera will contribute to development and hold commercialization rights in Japan and selected Asia Pacific markets.

Idorsia Ltd (SIX: IDIA) announced the initiation of FAB-KLEAR, the pivotal Phase 3 kidney biopsy study of lucerastat in adult patients with Fabry disease, and a co-development and commercialization agreement with Nxera Pharma Co., Ltd. (Nxera).

The agreement strengthens the global development of lucerastat through shared investment in the Phase 3 program and grants Nxera exclusive development and commercialization rights in Japan and selected Asia Pacific territories (ex-China). Following exercise of its pre-existing option, Nxera will pay Idorsia CHF 7 million and contribute to the global Phase 3 development program. Idorsia remains eligible to receive royalties on net sales in the licensed territories.

Roland Wandeler, CEO of Idorsia, commented:
“With a clearly defined regulatory pathway, compelling long-term clinical experience, and now the support of Nxera as a development and commercialization partner, we are entering an important new phase for lucerastat. The decision by Nxera to exercise its option and invest alongside us represents a significant endorsement of both the program and the opportunity to change the treatment paradigm for people living with Fabry disease. As we advance development, this partnership brings shared investment, complementary capabilities, and a common commitment to making lucerastat available to patients worldwide.”

Lucerastat is an investigational, oral substrate reduction therapy designed to treat Fabry disease independently of α-Gal A activity, type of GLA mutation, or prior treatment with enzyme replacement or chaperone therapy.

FAB-KLEAR is part of an FDA-aligned registration strategy designed to confirm lucerastat's ability to reduce renal globotriaosylceramide (Gb3) accumulation, a key driver of kidney disease in Fabry disease, and support a regulatory filing as early as 2029. Consistent with regulatory guidance for histology-based studies, FAB-KLEAR will enroll a small, highly characterized population of 16 treatment-naïve or pseudo-naïve (previously treated but not receiving Fabry disease-specific therapy for at least 6 months) adult male patients, a population selected to maximize the ability to detect changes in kidney Gb3 accumulation.

Progressive kidney disease remains one of the most serious manifestations of Fabry disease and a major cause of long-term morbidity. Protecting kidney function is therefore a key treatment objective for patients living with the disease.

Amer Joseph, MD, Chief Medical Officer and Head of Global Clinical Development at Idorsia commented:
“The recently published Phase 3 MODIFY study and its long-term extension have provided strong evidence of lucerastat’s disease-modifying potential. While the primary endpoint of neuropathic pain reduction was not met, a subjective outcome that is proving difficult to reach in Fabry disease, lucerastat demonstrated robust and sustained biomarker reductions and a promising signal for slowing renal function decline in patients. The next step is to generate the baseline-controlled data required by authorities for registration.”

Christopher Cargill, President and CEO of Nxera Pharma, added:
“The clinical evidence generated to date, together with the defined Phase 3 development program, gives us confidence in the potential of lucerastat for people living with Fabry disease. We look forward to working closely with Idorsia to advance development and bring this potential new treatment option to patients across our territories.”

Prof. Dominique P Germain, MD PhD, University of Versailles / Paris-Saclay University, Head of the Division of Medical Genetics at the Raymond Poincaré Hospital, and Investigator in Idorsia’s Fabry disease development program, commented:
“We have now followed some patients receiving lucerastat for more than six years, generating over 400 patient-years of safety and efficacy experience, something rarely achieved for an investigational therapy in a rare disease program. The findings from our previous work with lucerastat suggest that it may offer long-term kidney protection and broaden therapeutic options for Fabry patients, especially those underserved by current treatments. I’m very pleased that Idorsia together with the regulatory authorities have established a clear development pathway for further evaluation of lucerastat in Fabry disease. I look forward to playing my role in the program for the Fabry community.”

The broader Phase 3 program will also include a 74-patient comparative renal function study, FAB-SWITCH, evaluating lucerastat against standard-of-care enzyme replacement therapies, designed to establish lucerastat as the first oral therapy addressing the full spectrum of Fabry patients. Together, these complementary studies are expected to support a regulatory filing as early as 2029. Idorsia has aligned the development strategy of the Phase 3 program with the US FDA. The design of the program is also consistent with feedback received from the European Medicines Agency during previous regulatory interactions.