Japan's first oral therapeutic agent for Fabry disease

May 30, 2018, Fabry's disease treatment medicine Migalastat hydrochloride (trade name Galafold capsule 123 mg) was released. Adaptation is "Fabry disease accompanied by reactive GLA gene mutation of Migallastat", dosage regimen "Oral administration of 123 mg once every day for patients over the age of 16. In principle, to set the administration time constant every time And administration by avoiding 2 hours before and after eating because pharmacokinetic parameters (Cmax, AUC) are affected by meals. "

Fabry disease is one of "lysosomal diseases" that the country designates intractable disease (specific intractable disease).

Due to the deletion of α-galactosidase A (α-Gal A) by mutation of the GLA gene, glycosphingolipid, including its substrate globotriosylceramide (GL-3), is expressed in vascular endothelial cells, smooth muscle cells, It is an X chromosome recessive genetic disease that accumulates in ganglion cells and the like. Fabry disease is classical type that exhibits typical Fabry disease symptoms such as limb pain, hypohidrosis, skin angular hemangioma, renal failure, cardiac hypertrophy, heart type confined to the symptoms of the heart, symptoms of the kidneys There are no racial differences in incidence and it is reported as 1 in about 100,000 to 400,000 people.

Conventionally, symptomatic treatments such as carbamazepine (Tegreto et al.) And the like were used for treatment of Fabry disease for limb pain, but enzyme replacement therapy of agalcidase beta (Fabrazyme) and agalcidase alpha (repreparal) was introduced and effective Improvement of sex was aimed. However, on the other hand, both drugs are intravenous drip infusion preparations, and it has been a problem that there are many burdens on patients such as chills, fever and other allergic reactions due to administration develop.

Migarastat is an analogue of terminal galactose of glycosphingolipid and promotes proper transport of α-Gal A to the lysosome by binding to mutant α-Gal A as a pharmacological chaperone, It is an oral preparation having a new mechanism of action different from existing enzyme supplement formulation which increases α-Gal A activity.

Effectiveness and safety in the international joint Phase III trial until approval (target: Fabry disease patients including Japanese in switching from enzyme replacement therapy) and overseas Phase III trial (subject: untreated Fabry disease patients) Was confirmed. Overseas, as of March 2018, it has been approved in Europe, Australia, Canada, Israel, South Korea and Switzerland. In Japan, it is designated as a drug for rare diseases in April 2017. However, among the known genetic mutations in the GLA gene, there is a reactive genetic mutation to Migallastat and there is a gene mutation, so we confirmed "GLA mutation reactive with garafardo" to the manufacturing and selling company It is supposed to be.