In short
Migalastat hydrochloride is a chemical substance investigated as a medicine for Fabry disease, a rare inherited condition. It is already authorised in the EU for patients aged 12 and older under the brand name Galafold. One authorised clinical trial is currently testing a dispersible tablet form in children aged 2 to under 12 years with Fabry disease and amenable GLA variants, with a planned enrollment of 8 participants.
Key points
- Phase 3 open-label trial of migalastat hydrochloride in children aged 2 to under 12 years with Fabry disease.
- The trial has a planned enrollment of 8 participants.
- The trial is authorised and will evaluate safety, pharmacokinetics, pharmacodynamics, and efficacy over 12 months.
- Migalastat is already authorised in the EU as Galafold for patients aged 12 and older.
- The paediatric trial uses a dispersible tablet given orally at 140 mg.
- Migalastat works by stabilising the alpha-galactosidase A enzyme so it can break down GL-3.
What is migalastat hydrochloride?
Migalastat hydrochloride is a chemically synthesised small-molecule substance. It is the active ingredient in the medicine Galafold, which is authorised in the European Union for the treatment of Fabry disease in patients aged 12 years and older. Fabry disease is a rare inherited disorder in which mutations in the gene that produces the enzyme alpha-galactosidase A mean the enzyme does not work properly. As a result, a fatty substance called globotriaosylceramide (GL-3) builds up in various cells of the body, including in the heart and kidneys.
In the product records for the paediatric trial, migalastat hydrochloride is described as an investigational substance with no marketing authorisation for this specific paediatric formulation. It has received orphan designation for Fabry disease, which is a status given to medicines intended for rare diseases. The product name listed in the registry is Migalastat Hydrochloride Dispersible Tablet, supplied by Amicus Therapeutics.
How does migalastat hydrochloride work?
Migalastat attaches to certain unstable forms of the alpha-galactosidase A enzyme and stabilises it. This stabilisation allows the enzyme to be transported to the areas of the cell where it can break down GL-3. By helping the body's own enzyme to function, migalastat addresses the underlying enzyme deficiency in Fabry disease. This mechanism is specific to patients who have certain mutations, known as amenable GLA variants, in the alpha-galactosidase A gene.
Which conditions is it used or studied for?
- Fabry disease — a rare inherited disorder where the body cannot break down a fatty substance called GL-3, leading to its accumulation in cells and organs. The authorised paediatric trial is studying migalastat in children aged 2 to under 12 years with Fabry disease and amenable GLA variants.
How is migalastat hydrochloride given?
Migalastat hydrochloride is given orally. The authorised medicine Galafold is available as capsules, with a recommended dose of one capsule every other day. Patients should not eat for at least two hours before and two hours after taking Galafold to allow full absorption. The NHS dm+d browser lists migalastat 123 mg capsules with an oral route of administration.
For the paediatric trial, a dispersible tablet formulation is being used, with a dose of 140 mg given orally. This formulation is prepared for children, and the trial includes a paediatric formulation designation in its product records. An earlier extension study in adults and adolescents used an oral dose of 150 mg of migalastat hydrochloride every second day.
What do the clinical trials show?
The paediatric trial registered in the EU Clinical Trials Information System is a Phase 3, open-label, interventional study. It is authorised and plans to enroll 8 participants. The trial aims to characterise the pharmacokinetics of migalastat — that is, how the drug is absorbed, distributed, and eliminated from the body — and to confirm paediatric dose regimens predicted to provide plasma migalastat exposure levels similar to those seen in adolescents and adults. It will also evaluate safety in children aged 6 to under 12 years and 2 to under 6 years with Fabry disease and amenable GLA variants.
The primary outcomes include derived pharmacokinetic parameters for dosing confirmation, as well as safety measures such as the incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events leading to discontinuation of the study drug. The trial will also measure changes from baseline in clinical laboratory test results, vital signs, physical examination findings, body weight and height, ECG results, echocardiogram parameters, and Tanner stage for female subjects aged 8 years and older and male subjects aged 9 years and older.
An earlier Phase 3 open-label extension study evaluated the long-term safety and efficacy of migalastat hydrochloride monotherapy in subjects with Fabry disease. This study was funded by GlaxoSmithKline and expected at least 100 subjects to be eligible, with approximately 10 participants recruited in the UK. Participants received an oral dose of 150 mg of migalastat hydrochloride every second day.
What side effects are known?
The summary of product characteristics for Galafold, published by the European Medicines Agency, does not list specific side effects in the provided excerpt. The paediatric trial will measure the incidence of treatment-emergent adverse events, serious adverse events, and adverse events leading to discontinuation of the study drug, which will provide safety data for this age group.