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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.

Allschwil, Switzerland – October 28, 2026
Idorsia Ltd (SIX: IDIA) today 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.

About FAB-KLEAR
FAB-KLEAR is an open-label study that will enroll 16 treatment-naïve or pseudo-naïve adult male patients with Fabry disease. The study is designed to assess the potential for lucerastat to reduce kidney Gb3 accumulation, a key driver of Fabry-related kidney disease, through the primary endpoint of change from baseline to Month 18 in kidney Gb3 BLISS score (average number of Gb3 inclusions per kidney peritubular capillary (PTC)). A decrease from baseline to Month 18 in kidney Gb3 BLISS score indicates a reduction in the average number of Gb3 inclusions per peritubular capillary and therefore evidence of a histological treatment effect on kidney Gb3. The study will also measure the change from baseline to Month 18 in plasma Gb3 concentration, as well as assessing the safety and pharmacokinetic profile of lucerastat.

Data supporting lucerastat in Fabry disease
Results from the Phase 3 MODIFY study and its long-term extension demonstrated robust and sustained reductions in plasma and urinary Gb3 levels. In addition, long-term follow-up showed a slower rate of kidney function decline compared with the pre-treatment period, with particularly pronounced effects observed in patients with more severe disease, including males with classic Fabry disease, patients with anti-drug antibodies (ADA) against ERT, and patients with impaired renal function at baseline.

Kidney biopsy data from patients treated with lucerastat (n=6) for a median of almost five years further demonstrated low-to-no levels of kidney Gb3 inclusions, supporting the rationale for the ongoing pivotal biopsy study.

About the agreement
As part of the transaction regarding the sale of Idorsia’s Asia Pacific (ex-China) operations in July 2023 (press release), Idorsia had granted Nxera an option for a regional license for lucerastat. Under the new agreement, Nxera will receive exclusive rights to develop and commercialize lucerastat in Japan and selected Asia Pacific territories (ex-China). Nxera will pay an upfront of CHF 7 million as per pre-agreed option terms and contribute to the global Phase 3 development program. Idorsia is eligible to receive royalties on net sales in the licensed territories. The companies will work together to advance lucerastat through the Phase 3 program and support its potential registration in multiple territories.

Notes to the editor

About Fabry disease
Fabry disease is a rare, X-linked lysosomal storage disorder caused by mutations in the GLA gene that results in the absence or markedly reduced activity of the enzyme α-galactosidase A (α-GalA). α-GalA normally breaks down a lipid known as globotriaosylceramide (Gb3) in the cells of the body. Deficiency over time results in an accumulation of Gb3 deposits throughout the body, leading to multisystem disease, mainly affecting the kidneys, heart, and nervous system.

The disease manifests in two main phenotypes: classic Fabry disease, typically presenting in childhood with severe, multisystemic involvement, and late-onset Fabry disease, which may emerge in adulthood with predominant cardiac or renal symptoms. Fabry disease affects a patient’s life expectancy and quality of life. Due to its variable presentation and non-specific symptoms, Fabry disease is frequently underdiagnosed or misdiagnosed, leading to delays in treatment and increased risk of irreversible organ damage.

As the gene responsible for Fabry disease is found on the X chromosome (of which males have one, and females two), males with deleterious mutations have little or no residual alpha-GalA activity. Therefore, these male patients with Fabry disease experience a wider spectrum of symptoms, and in some cases, a greater severity. It is now widely accepted that women with Fabry disease are heterogeneous with respect to disease severity and may sometimes also develop life threatening complications of the disorder. Up to 70% of female carriers develop Fabry related symptoms at some point in their life.

According to DelveInsight, approximately 16,000 patients were diagnosed with Fabry disease across the seven major markets (US, EU4, UK, Japan) in 2020, a number expected to increase to roughly 21,000 by 2034. The Fabry disease market is projected to reach around USD 4 billion by 2034, underscoring the continued demand for innovative, patient-focused therapies.

About lucerastat
Lucerastat is an investigational, oral substrate reduction therapy designed to treat Fabry disease independently of α-Gal A activity, GLA mutation status, or prior enzyme replacement therapy. It acts by inhibiting glucosylceramide synthase, thereby reducing the synthesis of glycosphingolipids, including globotriaosylceramide (Gb3), which accumulate due to deficient α-galactosidase A activity in Fabry disease.

About lucerastat in Fabry disease
MODIFY was a multicenter, double-blind, randomized, placebo-controlled, Phase 3 study evaluating lucerastat as an oral monotherapy for adults with Fabry disease. A total of 118 patients from 14 countries were randomized 2:1 to lucerastat or placebo. Upon completion of the double-blind period, 107 patients entered a long-term OLE assessing safety, tolerability, and renal outcomes. Primary results from MODIFY and the 12-month interim OLE analysis have been published in Nature Communications, (“Lucerastat, an oral therapy for Fabry disease: Results from a pivotal phase 3 study and its open-label extension”, January 2026).

While the MODIFY study did not meet its primary endpoint of reducing neuropathic pain over six months, lucerastat demonstrated a robust pharmacodynamic effect, significantly reducing plasma and urinary Gb3 levels compared to placebo. These reductions were sustained over time in the OLE, with patients switching from placebo to lucerastat showing similar biomarker reductions. More importantly, as presented at WORLDSymposium™ 2026, an interim analysis of the OLE, where ongoing patients had been treated with lucerastat for at least 42 months – some exceeding six years of continuous therapy – revealed a notable shift in renal function trajectory. Treatment with lucerastat was associated with a reduction in the rate of eGFR decline as compared to eGFR slope observed in the 2 years preceding their enrollment in MODIFY (eGFR slope, historical: -3.50; Lucerastat: -1.64). Lucerastat treatment was also associated with a particularly marked attenuation of kidney function loss in patients with severe disease course, such as classic males with Fabry disease (historical: -4.32; Lucerastat: -2.05), patients with impaired renal function at baseline (eGFR <90 mL/min/1.73m2) (historical: -6.18; Lucerastat: -2.49), Anti-Drug Antibody (ADA+) positive patients (historical: -7.75; Lucerastat: -3.43). The effect was independent of the gene variants’ amenability to migalastat. Lucerastat also led to a 51% decrease in plasma Gb3 levels and was well-tolerated with long-term treatment. As the next steps in the Phase 3 program are underway, the OLE study was concluded and participants still receiving lucerastat at study closure were moved to a post-trial access program ensuring continuity of care. (Wallace E., et al. Mol Genet Metab. 2026;147(2):109659)

In addition, the positive impact on kidney function was supported by a kidney biopsy sub-study of six male adult patients with classic Fabry disease who had received lucerastat monotherapy for a median treatment period of 56 months. The study evaluated the number of kidney Gb3 inclusions using established quantitative (Barisoni Lipid Inclusion Scoring System (BLISS)) and semi-quantitative (Fabrazyme Scoring System (FSS)) methodologies. At enrollment in MODIFY, 4 participants were ERT naïve or pseudo-naïve and 2 switched from ERT. Median kidney Gb3 BLISS score was 1.7 (range: 0.7–4.5; mean (SD): 2.41 (1.59)). Mean FSS scores were 0 indicative of “no or trace” accumulation (5/6 participants) or 1 indicative of mild accumulation (1/6). The 2 patients who switched from ERT had BLISS scores of 1.6-1.8 and a FSS score of 0. The results indicate that long-term treatment with lucerastat monotherapy was associated with low-to-no levels of kidney Gb3 inclusions. (Germain DP., et al. Mol Genet Metab. 2026;147(2):109423)

In the MODIFY study, lucerastat was well tolerated. No clinically meaningful changes in vital signs or ECGs or marked laboratory abnormalities were observed. Two patients in each group (lucerastat 2.5%; placebo 5.4%) discontinued treatment due to adverse events. Serious adverse events were reported in 5 patients (6.3%) in the lucerastat group and in 1 patient (2.7%) in the placebo group.

Lucerastat for Fabry disease has received orphan drug designation in the US and the EU.

About Prof. Germain
Dominique P Germain, MD PhD is Professor of Medical Genetics at the University of Versailles (UVSQ) and Paris-Saclay University, and the Head of the Division of Medical Genetics at the Raymond Poincaré Hospital (APHP – University Paris Saclay).

Professor Germain graduated in medicine (MD, Dermatology), from the University of Nancy, France. He completed a Doctorate in Human Genetics (PhD) at the University Paris VII – Denis Diderot. He obtained his Habilitation in 2005 from the University Paris V – René Descartes. In 2006, he was appointed Director of the French Referral Centre for Fabry Disease by the French Ministry of Health, a position which he has kept ever since. In 2016, Professor Germain was appointed Director of a European Referral Centre for rare disorders (MetabERN: rare metabolic diseases) at the Hôpitaux Universitaires Paris Ile de France Ouest. In 2017, he also became the Director of a Centre of Expertise for birth defects and rare disabling congenital malformations.

Professor Germain’s research interests include the clinical and biochemical genetics of lysosomal storage disorders. He has a strong interest in enzyme replacement therapies, chaperon therapies, substrate reduction therapies and gene therapies. Throughout his career, Professor Germain has contributed extensively on the topics of Fabry disease, lysosomal storage diseases and neuro-muscular genetic diseases. He has contributed to several international and multi-disciplinary guidelines, has authored several book chapters and has published over 160 peer-reviewed articles, most of them as a lead or senior author including publications in The New England Journal of Medicine, The American Journal of Human Genetics and Genetics in Medicine. Prof. Germain serves as a consultant to Idorsia.

About Idorsia
The purpose of Idorsia is to discover, develop and commercialize innovative medicines to help more patients. To achieve this, we will develop Idorsia into a leading biopharmaceutical company, with a strong scientific core.

Headquartered near Basel, Switzerland – a European biotech hub – Idorsia has a highly experienced team of dedicated professionals, covering all disciplines from bench to bedside; QUVIVIQ™ (daridorexant), a different kind of insomnia treatment with the potential to revolutionize this mounting public health concern; strong partners to maximize the value of our portfolio; a promising in-house development pipeline; and a specialized drug discovery engine focused on small-molecule drugs that can change the treatment paradigm for many patients. Idorsia is listed on the SIX Swiss Exchange (ticker symbol: IDIA).

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