Across All Subgroups, Patients Treated with Migalastat Compare Favorably to Natural History on Kidney Function (eGFR)
Additional GL-3 Data Further Validate Assay for Identifying Patients with Amenable Mutations
CRANBURY, N.J., and SAN DIEGO, Oct. 19, 2014 (GLOBE NEWSWIRE) -- Amicus Therapeutics (Nasdaq:FOLD), a biopharmaceutical company at the forefront of therapies for rare and orphan diseases, today announced additional positive data from a Phase 3 study (Study 011) of the oral small molecule chaperone migalastat HCl ("migalastat") in Fabry disease patients with amenable mutations. In a poster at the American Society of Human Genetics (ASHG) Annual Meeting, Daniel G. Bichet, M.D., M.Sc., Professor, Department of Physiology, University of Montreal, presented results from patients in Study 011 including those who continued on migalastat in an open-label extension (Study 041).
Assessment of kidney function by various measures of glomerular filtration rate (GFR) for patients receiving migalastat in Study 011 for at least 18 months and continuing migalastat treatment in Study 041 showed continued stability of kidney function for an average of 32 months. Decline in kidney function is a key cause of morbidity and mortality in patients with Fabry disease. Measured (iohexol) GFR (mGFR) showed stability over 18-24 months in Study 011 but was not collected in Study 041; mGFR was previously reported with topline Study 011 results.
| Mean Annualized Change in GFR (ml/min/m2/yr) (SEM) |
Over an Average of 32 Months with Migalastat in 011 and 041
|Estimated GFR (eGFR) (CKD-EPI) (n=41)||-0.20 (0.60)|
|eGFR (MDRD) (n=41)||+0.63 (0.08)|
Stratifying patients for gender and baseline proteinuria demonstrated that patients treated with migalastat experienced less decline in kidney function than untreated patients from a previously published natural history study1.
Dr. Daniel Bichet, Full Professor and Section Head, Renal Function & Transport Physiology, University of Montreal, said, "Baseline proteinuria levels are among the most predictive indicators of disease prognosis and kidney function decline in Fabry patients. The data presented today show that when comparing patients with similar levels of proteinuria, patients treated with migalastat are more stable in their kidney function versus untreated patients. These results are very encouraging for migalastat as a treatment for Fabry patients with amenable mutations."
Data from a subgroup analysis comparing the change in GL-3 substrate levels between amenable patients and non-amenable patients based on the GLP HEK cell assay provided additional validation of the sensitivity of the GLP HEK assay for identifying patients who will respond to migalastat monotherapy. Overall, patients with amenable mutations had declining levels of GL-3 when treated for six months with migalastat. In contrast, patients with non-amenable mutations had no change or increasing levels of GL-3 after six months of migalastat treatment.
"We are pleased to present these additional Phase 3 results in a scientific forum. With 32 months of data, Fabry patients treated with migalastat exhibit long-term stability in their kidney function. These results contrast with the decline in kidney function reported in natural history studies. Decline in kidney function is one of the primary causes of morbidity and mortality in Fabry patients," stated Dr. Jay A. Barth, Chief Medical Officer of Amicus Therapeutics, Inc. "The additional data on substrate reduction show that we can accurately identify patients who may benefit from migalastat. We look forward to meeting with regulatory agencies starting this quarter as we work to make migalastat available for all amenable Fabry patients as quickly as possible."
About GLP HEK-Amenable Mutations
Amenable mutations are defined as having an absolute increase of 3% of wild type alpha-Gal A enzyme activity and a relative increase of 20% when exposed to migalastat in a cell-based in vitro assay. All patients enrolled in Study 011 had amenable mutations in the clinical trial HEK assay available at study initiation ("clinical trial assay"). Following the completion of enrollment, a GLP HEK assay was developed with a third party to measure the criteria for amenability with more quality control and rigor. However, approximately 10% of mutations in the HEK database switched categorization between "amenable" and "non-amenable" when moving from the clinical trial assay to the GLP HEK assay. Therefore, there were changes in categorization from amenable to non-amenable in 17 patients in Study 011.
Overall based on results from mutations tested in the GLP HEK assay, Amicus estimates that approximately 30% to 50% of the Fabry population has mutations that are amenable to migalastat.
About Amicus Therapeutics
Amicus Therapeutics (Nasdaq:FOLD) is a biopharmaceutical company at the forefront of therapies for rare and orphan diseases. The Company is developing novel, first-in-class treatments for a broad range of human genetic diseases, with a focus on delivering new benefits to individuals with lysosomal storage diseases. Amicus' lead programs include the small molecule pharmacological chaperones migalastat as a monotherapy and in combination with enzyme replacement therapy (ERT) for Fabry disease; and AT2220 (duvoglustat) in combination with ERT for Pompe disease.
1Schiffmann et al., Nephrol Dial Transplant (2009)
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