What side effects are associated with this type of intervention?

Common treatments for Gaucher Disease include enzyme replacement therapy (ERT) and substrate reduction therapy (SRT). ERT, such as Cerezyme, can cause infusion-related reactions including fever, chills, and allergic reactions. Long-term use may lead to antibody formation. SRT, which includes drugs like Venglustat, can cause gastrointestinal issues such as diarrhea, nausea, and abdominal pain, as well as fatigue and headache. Both therapies require monitoring for potential adverse effects to ensure patient safety.

What prior FDA approvals exist?

The FDA has approved several treatments for Gaucher Disease, primarily focusing on enzyme replacement therapies (ERT) and substrate reduction therapies (SRT). ERTs like Cerezyme (imiglucerase), Vpriv (velaglucerase alfa), and Elelyso (taliglucerase alfa) are commonly used. For SRT, drugs like Cerdelga (eliglustat) and Zavesca (miglustat) have been approved. Venglustat, a Glucosylceramide Synthase Inhibitor, is being studied as a potential treatment, similar to Cerdelga, which also inhibits glucosylceramide synthase to reduce the substrate accumulation in Gaucher Disease.

What other types of research exist?

Promising novel alternatives to Venglustat for Gaucher Disease patients in 2024 include: 1. Eliglustat (another SRT that has shown efficacy in Gaucher Disease Type 1). 2. Gene therapy approaches, such as those targeting the GBA gene to correct the underlying genetic defect. 3. Newer enzyme replacement therapies that may offer improved efficacy or reduced infusion frequency. 4. Other investigational SRTs that are currently in clinical trials and showing positive results.

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Substrate Reduction Therapy

Venglustat vs Imiglucerase for Gaucher Disease (LEAP2MONO Trial)

Q: What is the mechanism of action of this treatment?

Gaucher Disease is commonly treated with enzyme replacement therapy (ERT) and substrate reduction therapy (SRT). ERT involves the intravenous administration of recombinant glucocerebrosidase to replace the deficient enzyme in patients, thereby reducing the accumulation of glucocerebroside in cells. SRT, including Glucosylceramide Synthase Inhibitors like Venglustat, works by inhibiting the synthesis of glucosylceramide, the substrate that accumulates due to the enzyme deficiency. This reduction in substrate production helps to balance the reduced enzyme activity, alleviating symptoms and preventing further damage. These treatments are crucial for managing Gaucher Disease as they address the underlying biochemical defect, improving quality of life and preventing severe complications.

Phase 3

Waitlist Available

Research Sponsored by Genzyme, a Sanofi Company

Eligibility Criteria Checklist

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

Must have

The participant has a modified SARA score of 1 or above

Adult participant is ≥18 years of age

Must not have

Prior esophageal varices or liver infarction or current liver enzymes (alanine aminotransferase [ALT]/ aspartate aminotransferase [AST]) or total bilirubin >2 times the upper limit of normal, unless the participant has a diagnosis of Gilbert Syndrome

The participant has renal insufficiency, as defined by an estimated glomerular filtration rate <30 mL/min/1.73m2 at the screening visit

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial compares a pill to injections in patients aged 12-18 and adults with Gaucher disease Type 3. The pill aims to help with brain symptoms, while the injections maintain overall health. The pill has the potential to improve Gaucher disease by rebalancing certain substances in the body.

Who is the study for?

This trial is for adults and children aged ≥12 with Gaucher Disease Type 3 (GD3) who have been on Enzyme Replacement Therapy for at least 3 years. They must not be pregnant, breastfeeding, or planning to donate sperm; should weigh over 30 kg; and have controlled seizures if present. Exclusions include those needing ventilatory support, with allergies to study drugs, recent use of certain CYP3A affecting substances including grapefruit products, history of cancer (except basal cell carcinoma), planned hospitalizations, significant other diseases or conditions that could interfere with the study.

What is being tested?

The trial compares the effectiveness and safety of an oral drug called Venglustat against intravenous infusions of Imiglucerase (Cerezyme). It's designed as a Phase 3 study where participants are randomly assigned to one of two groups: one taking Venglustat daily by mouth and the other receiving Cerezyme injections every two weeks. The goal is to see which treatment better improves or stabilizes neurological symptoms while maintaining overall health in GD3 patients.

What are the potential side effects?

While specific side effects aren't listed here, common ones associated with medications like Venglustat may include stomach issues, fatigue, headache, dizziness or allergic reactions. For Imiglucerase infusions such as Cerezyme side effects can range from discomfort at injection site to more serious immune responses.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My balance and coordination are affected.

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I am 18 years old or older.

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I weigh at least 30 kg.

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I have been diagnosed with Gaucher's disease type 3.

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I have difficulty moving my eyes side to side quickly.

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I am between 12 and 17 years old.

Exclusion Criteria

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

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My liver function tests are not more than twice the normal limit, unless I have Gilbert Syndrome.

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My kidney function is low, with a filtration rate under 30 mL/min.

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I have had a major organ transplant.

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I need a breathing machine for more than 12 hours a day while awake.

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I have had cancer before, but not skin cancer (basal cell carcinoma).

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I will be hospitalized for surgery during the study.

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I need a machine to help me breathe.

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I need regular blood transfusions to manage my condition.

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I have been diagnosed with progressive myoclonic epilepsy.

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

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

2Treatment groups

Experimental Treatment

Active Control

Group I: VenglustatExperimental Treatment1 Intervention

Venglustat

Group II: CerezymeActive Control1 Intervention

Cerezyme

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Venglustat

2018

Completed Phase 1

~90

0 / 15Eligibility 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

Gaucher Disease is commonly treated with enzyme replacement therapy (ERT) and substrate reduction therapy (SRT). ERT involves the intravenous administration of recombinant glucocerebrosidase to replace the deficient enzyme in patients, thereby reducing the accumulation of glucocerebroside in cells. SRT, including Glucosylceramide Synthase Inhibitors like Venglustat, works by inhibiting the synthesis of glucosylceramide, the substrate that accumulates due to the enzyme deficiency. This reduction in substrate production helps to balance the reduced enzyme activity, alleviating symptoms and preventing further damage. These treatments are crucial for managing Gaucher Disease as they address the underlying biochemical defect, improving quality of life and preventing severe complications.