Date: 2016-11-11
Type of information: Publication of results in a medical journal
phase: 3
Announcement: publication of results in the Journal of Medical Genetics
Company: Amicus Therapeutics (USA - NJ)
Product: migalastat
Action
mechanism: chaperone. Fabry disease is an inherited lysosomal storage disorder caused by deficiency of an enzyme called alpha-galactosidase A (alpha-Gal A). The role of alpha-Gal A within the body is to break down specific lipids in lysosomes, including globotriaosylceramide (GL-3, also known as Gb3). Lipids that can be degraded by the action of alpha-Gal are called "substrates" of the enzyme. Reduced or absent levels of alpha-Gal A activity leads to the accumulation of GL-3 in the affected tissues, including the kidneys, heart, central nervous system, and skin. Migalastat HCl is designed to bind to and stabilize, or "chaperone" a patient's own alpha-galactosidase A (alpha-Gal A) enzyme in those patients with genetic mutations that are amenable to this chaperone in a cell-based assay. This assay (Galafold Amenability Assay) was used to classify more than 800 known GLA mutations as "amenable" or "not amenable" to treatment with Galafold. The current label includes all 269 GLA mutations that have been identified and determined to be amenable based on the Galafold Amenability Assay, which represent between 35% and 50% of the currently diagnosed Fabry population. Amicus commenced the commercial launch on May 31, 2016 following the European Commission's full approval for migalastat, under the trade name Galafold™, as a first line therapy for long-term treatment of adults and adolescents aged 16 years and older with a confirmed diagnosis of Fabry disease and who have an amenable mutation.
Disease: Fabry disease
Therapeutic area: Rare diseases - Genetic diseases
Country:
Trial
details: Study 012 was a Phase 3 open-label study that compared oral migalastat to standard-of-care Enzyme Replacement Therapies (ERTs) for Fabry disease (agalsidase alfa or beta). The study enrolled 60 patients (26 males and 34 females) with Fabry disease with amenable mutations in a clinical trial assay who had been treated with ERT for a minimum of 12 months prior to study entry. These patients were randomized 1.5:1 to switch to migalastat (36 patients) or remain on ERT (24 patients) for the primary 18-month treatment period. The co-primary outcome measures were the mean annualized changes in estimated glomerular filtration rate (eGFR) and measured (iohexol) GFR (mGFR) assessed by descriptive comparisons of migalastat and ERT over 18 months. Secondary outcome measures included left ventricular mass index (LVMi), as well as a composite of Fabry-associated clinical events (i.e. renal, cardiac, or cerebrovascular). Upon completion, patients were eligible to roll over into a separate extension to continue migalastat.
Latest
news: * On November 11, 2016, Amicus Therapeutics announced that data from the pivotal Phase 3 Study 012 (ATTRACT) evaluating the efficacy and safety of the oral pharmacological chaperone migalastat compared with Enzyme Replacement Therapy (ERT) in individuals with Fabry disease were published online in the Journal of Medical Genetics (Hughes, et al. Oral Pharmacological Chaperone Migalastat Compared With Enzyme Replacement Therapy in Fabry Disease: 18-Month Results from the Randomized Phase 3 ATTRACT Study, J Medical Genetics, online publication 10 November 2016. doi:10.1136/jmedgenet- 2016-104178). The study showed that migalastat and ERT had similar effects on renal function. Left ventricular mass index decreased significantly with migalastat treatment (?6.6?g/m2 (?11.0 to ?2.2)); there was no significant change with ERT. Predefined renal, cardiac or cerebrovascular events occurred in 29% and 44% of patients in the migalastat and ERT groups, respectively. Plasma globotriaosylsphingosine remained low and stable following the switch from ERT to migalastat.
