Lucerastat is an experimental treatment by Idorsia now in advanced clinical studies for Fabry disease. It functions as a substrate reduction therapy.

How does lucerastat work?

Fabry disease patients are unable to make the enzyme alpha-galactosidase A because of a mutation in the gene (GLAthat contains the information to make this enzyme. Alpha-galactosidase A is necessary to break down fat molecules called globotriaosylceramide (Gb3 or GL-3). Without the enzyme, Gb3 builds up inside cells and damages them, leading to disease symptoms.

Lucerastat is a small molecule called an “iminosugar,” and is almost identical to a sugar molecule except for the substitution of a nitrogen atom in place of an oxygen atom. It is designed to block production of another enzyme, glucosylceramide synthase, which plays a role in the production of Gb3. With less glucosylceramide synthase, less Gb3 is produced, and its build-up is lower even in the absence of alpha-galactosidase A.

Lucerastat in clinical trials

Lucerastat has been tested in three Phase 1 clinical trials in healthy volunteers to assess its safety, tolerability, and pharmacokinetics (movement in the body) at various doses. These trials showed that the medication was well-tolerated at all doses and did not cause any serious adverse events.

Lucerastat was also tested in a Phase 1 clinical trial (NCT02930655) in Fabry patients who were being treated with enzyme replacement therapy (ERT). This small, open-label exploratory trial included 10 people who were given oral lucerastat in addition to ERT, and four  who received ERT only. Its results showed that levels of Gb3 and related fats in the blood decreased significantly in the lucerastat group. The medication was also well-tolerated by adults with Fabry disease.

A Phase 3 clinical trial (NCT03425539), called MODIFY, is now assessing the safety and effectiveness of lucerastat (1,000 mg total; taken as two capsules twice daily) against placebo in adults with Fabry disease. Effectiveness at six months will be measured by patient-reported neuropathic pain, gastrointestinal symptoms, and Gb3 levels in the blood. This trial is currently recruiting up to 108 patients at sites across the U.S., Australia, Canada, and Europe; information is available here. Study results are expected in June 2021, when the trial concludes.

Patients who complete MODIFY will have the open of rolling into a Phase 3 long-term, open-label extension study (NCT03737214). Here, all will be given lucerastat for 24 months and then followed after another month. The study will monitor treatment-emergent adverse events, along with physiological measures like changes in Gb3 blood levels. It is expected to conclude in May 2022.


Last updated: Feb. 18, 2020


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