Rare Disease Report

The Effects of Migalastat on Fabry Disease and Amicus Stock Prices - Stage 1.

FEBRUARY 17, 2013
RDR Staff

Amicus had an eventful week last week. They had several presentations at the Lysosomal Disease Network (LDN) WORLD Symposium that many patients, researchers, and investors were eager to see. The most anticipated results were for its first phase 3 trial involving the effects of migalastat on patients with Fabry disease.  Migalastat is Amicus Therapeutics’ first chaperone therapy to be tested at that level.  However, for this first phase 3 study, migalastat is not being tested as a chaperone therapy but as a monotherapy where it is also believed to be effective.

 And the results from that study were – mixed.  At the symposium, the preliminary stage 1 results were presented [1] and the data did not meet the primary endpoint. However, like many treatment options for orphan diseases, things are not that black and white. The phase 3 study in question was migalastat monotherapy for Fabry Disease and the primary endpoint was a 50% reduction in kidney interstitial capillary GL-3 levels.  After 6 months of treatment, 28.1% (9 of 32) of placebo patients and 40.6% (13 of 32) of migalastat patients responded to treatment (ie, 50% lower IC-GL-3). That was not found to be a statistically significantly difference. However, the data only represents the first stage of the study. It is a 12 month study and stage 1 only represented the first 6 months of the placebo controlled study (stage 2 is a 6 month open label study).

migalastat RCT.png

During a webcast on Friday, CEO John Crowley and CSO David Lockhart reiterated that the data is still preliminary and more importantly, a post hoc analysis of the data seems to show that migalastat has a significant impact on a subpopulation of the study that the primary endpoint does not separate from the entire population. If data is collected only from patients with interstitial capillary GL-3 levels > 0.3, migalastat has a very significant affect whereas in patients with lower GL-3 levels, the response was not significantly different from baseline. This can be shown in the figure below that was presented in the Friday webcast.

migalostat mono - posthoc analyst 530.png

So what does all of this mean for patients, clinicians, and investors? That will likely depend on what the FDA says. Amicus plans to meet with the FDA later this year (mid 2013) after they have collected and analyzed the 12 month phase 3 data. At present, they expect to meet with the FDA  to discuss migalastat’s U.S. approval pathway. In the meantime, investors are being a bit pessimistic in the short term (stock declined 25% on Friday) while patients appear to like the drug in the long term. Dr. Lockhart said that the drug is well tolerated by the patients and Mr. Crowley noted that 57 of the 59 patients in the study have elected to continue to take migalastat in the ongoing study extension.

The webcast also provided an update on the latest clinical results with migalastat as a chaperone therapy for patients taking enzyme replacement therapy for Fabry disease. In the phase 2a study patients were given migalastat in combination with enzyme replacement therapy (ERT: Fabrazyme or Replagal). The study found that the addition of migalastat greatly increased the pharmacokinetics of the ERT drugs (ie, higher plasma rhGLA activity and mean skin GLA activity). [2] Similarly, results of a phase 2a study using chaperone therapy (AT2220) in combination with Myozyme/Lumizume in patients with Pompe disease was also presented at the symposium. [3] That study also observed the addition of chaperone technology to increase plasma AUC rhGAA activity and muscle GAA activity which indicate improved pharmacokinetic activity.

We look forward to seeing additional data from Amicus later this year. They have a strong pipeline with some great partners to compliment their own strong executive team. Should be an interesting year for the company.


1.Nicholls K, Germain DP, Feliciani C, et al. Phase 3 Study of Migalastat HCl for Fabry Disease: Stage 1 Results. Presented at: Lysosomal Disease Network WORLD Symposium; February 12-15, 2013; Orlando FL.

2.Warnock D, Bichet D, Holida M, et al. A Phase 2a Study to Investigate the Effect of a Single Dose of Migalastat HCl, a Pharmacological Chaperone, on Agalsidase Activity in Subjects with Fabry Disease . Presented at: Lysosomal Disease Network WORLD Symposium; February 12-15, 2013; Orlando FL.

3.Kishnani P et al. A Phase 2a Study to Investigate Drug?Drug Interactions between Escalating Doses of AT2220 (Duvoglustat Hydrochloride) and Acid Alfa?Glucosidase in Subjects with Pompe Disease. Presented at: Lysosomal Disease Network WORLD Symposium; February 12-15, 2013; Orlando FL.

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