Amicus Therapeutics has submitted a Japanese new drug application (J-NDA) to the Pharmaceuticals and Medical Devices Agency (PMDA) to request marketing authorization for migalastat, an oral precision medicine for Fabry disease.
John F. Crowley, Chairman and Chief Executive Officer of Amicus Therapeutics, Inc., stated, “On the heels of our initial commercial launch success for migalastat in the EU, we are pleased to submit our Japanese new drug application for migalastat. With more than 700 Fabry patients currently treated in Japan, we believe that a substantial number of Japanese Fabry patients could potentially benefit from migalastat as a differentiated precision oral therapy with a unique mechanism of action. Japan is a key part of our patient-focused vision to provide migalastat to amenable Fabry patients throughout the world as soon as possible. We look forward to working collaboratively with the PMDA toward a potential approval in the coming months.”
Based on a previous meeting with and written correspondence from the PMDA, the J-NDA is based upon data from completed clinical studies with migalastat, including two pivotal Phase 3 studies, as well as a Phase 1 study that evaluated the pharmacokinetics of migalastat in Japanese volunteers. Migalastat has orphan drug designation in Japan which makes it eligible for priority review as well as 10 years of market exclusivity, if approved. Based on the priority review timeline, Amicus expects a decision from the PMDA in the first half of 2018.
Japan represents the second largest Fabry market in the world by country, with approximately 13% of the $1.2B global Fabry ERT sales generated in Japan in 2016. Fabry disease is a rare genetic disease and potentially life-threatening condition caused by the accumulation of disease substrate (globotriaosylceramide, GL-3) in the lysosome due to a dysfunctional or deficient enzyme. Migalastat works by stabilizing the body’s own dysfunctional enzyme, so it can clear the accumulated disease substrate in patients who have amenable mutations. An amenable mutation is one that is responsive to therapy with migalastat based on a proprietary in vitro assay (Galafold Amenability Assay). Amicus estimates that 35%-50% of Fabry patients globally may have amenable genetic mutations, and amenability rates within this range vary by geography.
Migalastat is currently reimbursed in 11 countries in the EU and other parts of the world, on a commercial basis or through expanded access programs (EAPs). The European Commission granted 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 (alpha-galactosidase A deficiency) and who have an amenable mutation. The EC approval was based on clinical data from two Phase 3 pivotal studies in both treatment-naïve (Study 011, or FACETS) and enzyme replacement therapy (ERT) switch patients (Study 012, or ATTRACT), as well as ongoing long-term extension studies.
About Fabry Disease
Fabry disease is an inherited lysosomal storage disorder caused by deficiency of an enzyme called alpha-galactosidase A (alpha-Gal A), which is the result of mutations in the GLA gene. The primary biological function of alpha-Gal A is to degrade specific lipids in lysosomes, including globotriaosylceramide (referred to here as GL-3 and also known as Gb3). Lipids that can be degraded by the action of alpha-Gal A are called “substrates” of the enzyme. Reduced or absent levels of alpha-Gal A activity lead to the accumulation of GL-3 in the affected tissues, including the central nervous system, heart, kidneys, and skin. Progressive accumulation of GL-3 is believed to lead to the morbidity and mortality of Fabry disease, including pain, kidney failure, heart disease, and stroke. The symptoms can be severe, differ from patient to patient, and begin at an early age. All Fabry disease is progressive and may lead to organ damage regardless of the time of symptom onset.