What is the mechanism of action of this treatment?

Lucerastat, a Glucosylceramide Synthase Inhibitor, works by inhibiting the enzyme responsible for the synthesis of glucosylceramide, a precursor to glycosphingolipids. In Fabry Disease, the accumulation of glycosphingolipids due to deficient alpha-galactosidase A activity leads to cellular dysfunction and organ damage. By reducing the synthesis of these harmful substrates, Lucerastat aims to alleviate the burden on cells and tissues, potentially improving symptoms and slowing disease progression. This mechanism is crucial for Fabry Disease patients as it targets the underlying cause of lipid accumulation, offering a therapeutic approach that complements enzyme replacement therapies.

What side effects are associated with this type of intervention?

Common treatments for Fabry Disease include enzyme replacement therapy (ERT) and oral chaperone therapy. ERT, such as agalsidase beta and agalsidase alfa, can cause infusion-related reactions, including fever, chills, and fatigue, as well as potential allergic reactions. Oral chaperone therapy, like migalastat, may cause headaches, nausea, and abdominal pain. For treatments similar to Lucerastat, which is a Glucosylceramide Synthase Inhibitor, side effects may include gastrointestinal issues, such as diarrhea and abdominal pain, as well as potential liver enzyme elevations.

What prior FDA approvals exist?

Fabry Disease has been treated with enzyme replacement therapies (ERTs) such as agalsidase beta (Fabrazyme) and agalsidase alfa (Replagal), which were among the first FDA-approved treatments. These therapies work by replacing the deficient enzyme alpha-galactosidase A. More recently, chaperone therapy with migalastat (Galafold) has been approved, which stabilizes the enzyme's function. While Lucerastat, a Glucosylceramide Synthase Inhibitor, is still under study, it represents a novel approach by targeting substrate reduction therapy, aiming to reduce the accumulation of glycosphingolipids in cells.

What other types of research exist?

Promising novel alternatives to Lucerastat for Fabry Disease patients include: 1) Migalastat, a pharmacological chaperone that stabilizes the enzyme alpha-galactosidase A, improving its function. 2) Gene therapies such as FLT190, which aim to provide a long-term solution by correcting the underlying genetic defect. 3) Pegunigalsidase alfa, a novel enzyme replacement therapy designed to have a longer half-life and potentially improved efficacy compared to existing treatments.

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Substrate Reduction Therapy

Long-term Safety of Lucerastat for Fabry Disease

Phase 3

Waitlist Available

Research Sponsored by Idorsia Pharmaceuticals Ltd.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Must not have

Subject must not be enrolled in study ID-069A302 if at any time during study ID-069A301, one of the following criteria was met: Subject's eGFR per the Chronic Kidney Disease Epidemiology Collaboration creatinine equation < 15 mL/min/1.73 m2, Subject experienced an event of acute kidney injury Common Terminology Criteria for Adverse Event (CTCAE) grade 2 or above, Subject experienced an event of stroke CTCAE grade 3 or above, Subject experienced an event of heart failure leading to in-patient hospitalization or prolongation of ongoing hospitalization

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial is testing the safety and tolerability of a medication called lucerastat, which is taken by mouth. It is aimed at adults with Fabry disease, a condition where harmful fats build up in the body. Lucerastat helps to reduce these fat levels.

Who is the study for?

Adults with Fabry disease can join this trial if they've finished a previous 6-month study (ID 069A301). Women must use contraception and have monthly pregnancy tests. Men should use condoms and not father children. People with conditions that could affect the study or those at high risk for organ issues, pregnant, or lactating individuals cannot participate.

What is being tested?

The trial is testing the long-term safety of Lucerastat, an oral medication for adults with Fabry disease. It aims to understand how well patients tolerate this drug over an extended period following their initial treatment in a prior study.

What are the potential side effects?

While specific side effects are not listed here, the goal of the trial is to monitor how safe and tolerable Lucerastat is when taken by adults with Fabry disease over a long duration.

Eligibility Criteria

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I have not had severe kidney issues, stroke, or heart failure that required a hospital stay during the previous study.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Side effects data

From 2021 Phase 3 trial • 118 Patients • NCT03425539

14%

Nausea

11%

Headache

11%

Diarrhoea

10%

Nasopharyngitis

Flatulence

Pruritus

Vomiting

Neuralgia

Vaccination complication

Arthralgia

Back pain

Abdominal distension

Dry mouth

Abdominal pain

Fatigue

COVID-19

Muscle spasms

Ischaemic stroke

Ventricular tachycardia

Abdominal discomfort

Streptococcal bacteraemia

Vertigo

Drug withdrawal syndrome

Localised infection

Vertigo positional

Pleural effusion

Implantable defibrillator insertion

Hepatitis viral

Septic encephalopathy

100%

80%

60%

40%

20%

Study treatment Arm

Placebo

Lucerastat

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

1Treatment groups

Experimental Treatment

Group I: LucerastatExperimental Treatment1 Intervention

Dose will be based on subject's eGFR.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Lucerastat

Not yet FDA approved

0 / 1Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Lucerastat, a Glucosylceramide Synthase Inhibitor, works by inhibiting the enzyme responsible for the synthesis of glucosylceramide, a precursor to glycosphingolipids. In Fabry Disease, the accumulation of glycosphingolipids due to deficient alpha-galactosidase A activity leads to cellular dysfunction and organ damage. By reducing the synthesis of these harmful substrates, Lucerastat aims to alleviate the burden on cells and tissues, potentially improving symptoms and slowing disease progression. This mechanism is crucial for Fabry Disease patients as it targets the underlying cause of lipid accumulation, offering a therapeutic approach that complements enzyme replacement therapies.