Amicus Therapeutics (NASDAQ: FOLD) said Wednesday that its Fabry disease drug migalastat meets main goals in phase III study (Study 012). Do you know that this drug was so close to being killed?
Fabry disease is a rare genetic lysosomal storage disease caused by deficiency of an enzyme called α-galactosidase A (α-Gal). Deficiency of α-Gal leads to accumulation of globotriaosylceramide (GL-3), resulting in severe damage to various organs.
The current treatment for Fabry disease is enzyme replacement therapy (ERT) with Sanofi’s Fabrazyme or shire’s Replagal, both of which require intravenous infusions every two weeks. Migalastat is a pill which would be far easier for children to take.
Amicus conducted a placebo-controlled study to support US registration and an ERT-controlled study to support global registration, known as Study 011 and Study 012, respectively.
In December 2012, Amicus announced the 6-month results from Study 011. Migalastat demonstrated greater reduction in kidney interstitial capillary GL-3 than placebo, however, the difference was not statistically significant.
GlaxoSmithKline licensed migalastat from Amicus with $60 million upfront and $170 million milestone payments in October 2010. However, GlaxoSmithKline returned the rights to migalastat to Amicus after the failure in Study 011.
Fortunately, John Crowley, Amicus’ CEO, decided to stick with it.
Migalastat is a competitive α-Gal inhibitor which binds to and stabilizes patient’s endogenous α-Gal. Thereby, patients with too little native α-Gal or badly mutated α-Gal don’t benefit from migalastat monotherapy. Thus Amicus developed a HEK cell-based in vitro assay to screen patients with amenable mutations.
In April 2014, Amicus announced positive 12- and 24-month data from Study 011. Migalastat showed a statistically significant reduction in kidney interstitial capillary GL-3 in HEK amenable patients. According to John Crowley, at least 30% of Fabry patients have amendable mutations.
Four months later, Amicus disclosed phase III data from Study 012. Migalastat had a comparable effect to ERT on patients’ kidney function as measured by the change in eGFR and mGFR.
Amicus now owns 100% of the worldwide rights to migalastat. If all goes well, migalastat will be the first oral treatment for Fabry disease.
 Nat Med. 1999, 5(1), 112-115.