- Amicus Therapeutics (NASDAQ:FOLD) intends to submit a New Drug Application (NDA) to the FDA in Q4 seeking approval for lead product candidate migalastat in Fabry disease (FD), an inherited lysosomal storage disorder caused by a deficiency in an enzyme called alpha-galactosidase A which leads to the accumulation of a type of fat in the body's cells. The condition, affecting one in 40,000 to 60,000 males, leads to progressive kidney damage, heart attack and stroke.
- Based on FDA feedback in a recent pre-NDA meeting, the application will use the reduction in disease substrate (kidney interstitial capillary GL-3) as the primary endpoint. The filing will also include the protocol for a Phase 4 study of the effect of migalastat on gastrointestinal symptoms associated with FD. The NDA will be reviewed under the FDA's Accelerated Approval pathway.
- The current standard of care treatment for FD is enzyme replacement therapy (ERT). Migalastat, being a pharmacological chaperone, has a unique mechanism of action. Many FD sufferers produce some alpha-galactosidase A that is capable of degrading substrate but the genetic mutation prevents it from being delivered to lysosomes in sufficient amounts to reduce GL-3 (type of fat). Migalastat binds to and stabilizes alpha-galactosidase A which increases its trafficking to lysosomes (acts as a "chaperone") which increases the breakdown of GL-3. As many as 50% of FD patients have the amenable mutations to respond to migalastat monotherapy.
- The company is developing a next-generation therapy that combines migalastat with ERT that will potentially enable all FD patients to benefit from migalastat treatment.
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