Amicus Therapeutics Announces Positive Phase 3 Data on Cardiac Endpoints From Fabry Monotherapy Study 011 and Long Term Extension Study

Philadelphia, Pennsylvania, UNITED STATES

Statistically Significant Improvements in Key Cardiac Parameter in Fabry Patients Previously Naïve to Therapy

Continued Improvement Out to 36 Months on Key Cardiac Parameter

Further Strengthens Data Package for Upcoming Regulatory Submissions

CRANBURY, N.J., Jan. 8, 2015 (GLOBE NEWSWIRE) -- Amicus Therapeutics (Nasdaq:FOLD), a biopharmaceutical company at the forefront of therapies for rare and orphan diseases, today announced additional positive data on an important cardiac endpoint from its first Phase 3 study (Study 011) and the Phase 3 extension (Study 041) of the oral small molecule chaperone migalastat HCl ("migalastat") for Fabry disease. A slide presentation featuring these data is also available at  

Data from the Fabry Registry indicate that the leading cause of death in patients is from cardiovascular disease1. In Study 011 and Study 041, previously untreated patients with amenable mutations showed a statistically significant decrease in left ventricular mass index (LVMi) following treatment with migalastat for up to 36 months (average of 22 months). LVMi is a measure of cardiac hypertrophy, an increase in the size of the heart that has been associated with an increased risk of cardiac events in Fabry patients.

John F. Crowley, Chairman and Chief Executive Officer of Amicus Therapeutics, Inc. stated, "The effects of migalastat on Fabry patients with amenable mutations continue to be very profound. For the first time we are able to show that migalastat can lead to a reduction in LVMi in Fabry patients who are ERT-treatment naïve. These new data add to the positive cardiac effects that we showed in the ERT switch Study 012. Migalastat has now demonstrated a beneficial effect on LVMi in untreated Fabry patients for up to 36 months, which is twice as long of a treatment period as we previously reported in ERT switch patients from Study 012. What is perhaps most important in these results is that after 18 months we continue to see further significant reductions in cardiac mass. These data therefore strongly suggest that migalastat has a persistent and increasing positive effect on LVMi over longer periods of time. We believe that this positive effect is related to migalastat's unique mechanism of action, which is very distinct from currently approved therapies. The cardiac data from both of our Phase 3 studies, in addition to the favorable results on disease substrate reduction and stabilization of kidney function that we previously reported, represent a very compelling data package as we prepare to seek global approval of migalastat monotherapy."

Data Summary:

Left Ventricular Mass Index (LVMi) (g/m2)* in Phase 3 Study 011+041 – Change from Baseline to Last Available Time Point
  Migalastat Baseline Mean
(% abnormal)
Migalastat Change
(Mean, 95% CI)
Study 011+041 97.5 -8.0
(Avg 22 Months)** (26%) (-13.5, -2.5)***

*Read in blinded manner in centralized lab every 6 months. Normal LVMI: 43-95 (female), 49-115 (male)
**All amenable patients with baseline and post-baseline values
***Statistically significant (95% CI does not overlap zero)

Previously Reported Data in ERT Switch Patients (Study 012)

Previously reported data from the Phase 3 Study 012 showed a statistically significant decrease in LVMi following 18 months of treatment with migalastat in patients with amenable mutations who had switched from ERT.

Left Ventricular Mass Index (LVMI) (g/m2)** in Phase 3 Study 012 – Change from Baseline to Month 18*
  Migalastat Baseline Mean
(% abnormal)
Migalastat Change
(Mean, 95% CI)
ERT Baseline Mean
(% abnormal)
ERT Change
(Mean, 95% CI)
Study 012** 95.3 -6.6 92.9 -2.0
(18 Months) (39%) (-11.0, -2.1)*** (31%) (-11.0, +7.0)

*Read in blinded manner in centralized lab every 6 months. Normal LVMI: 43-95 (female), 49-115 (male)
**mITT population
***Statistically significant (95% CI does not overlap zero)

About Study 011

Study 011 was a Phase 3 study designed to measure the reduction of disease substrate (globotriaosylceramide, or GL-3) following treatment with migalastat. The study also measured clinical outcomes, including renal function and LVMi, as secondary endpoints.The 24-month study began with a 6-month double-blind, placebo-controlled treatment period, after which all patients were treated with migalastat for a 6-month open-label follow-up period and a subsequent 12-month open-label extension phase. Positive 12- and 24-month data on substrate reduction as well as renal function were previously reported.

Fabry patients enrolled in Study 011 were naïve to treatment or had not received enzyme replacement therapy (ERT) for at least 6 months prior to study entry. Upon completion, patients were eligible to roll over into a separate extension Study (Study 041) to continue migalastat.

About Study 012

Study 012 was a Phase 3, open-label study that compared oral migalastat to standard-of-care ERTs for Fabry disease (Fabrazyme® and Replagal®). The study enrolled 60 patients (26 males and 34 females) with Fabry disease with amenable mutations in a clinical trial assay who had been treated with ERT for a minimum of 12 months prior to study entry. These patients were randomized 1.5:1 to switch to migalastat (36 patients) or remain on ERT (24 patients) for the primary 18-month treatment period, after which they were eligible to receive migalastat in a 12-month extension phase.

The co-primary outcome measures were the mean annualized changes in estimated glomerular filtration rate (eGFR) and measured (iohexol) GFR (mGFR) assessed by descriptive comparisons of migalastat and ERT over 18 months. Secondary outcome measures included LVMi, as well as a composite of Fabry-associated clinical events (i.e. renal, cardiac, or cerebrovascular).

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 and Study 012 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, and in 4 patients in Study 012. 

Overall based on results from mutations tested in the GLP HEK assay, Amicus continues to believe that approximately 30% to 50% of the Fabry population have 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 in development include the small molecule pharmacological chaperone migalastat as a monotherapy for Fabry disease, as well as next-generation enzyme replacement therapy (ERT) products for Fabry disease, Pompe disease, and MPS-1.

1Mehta 2009

Forward-Looking Statements

This press release contains, and the accompanying conference call will contain, "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 relating to preclinical and clinical development of Amicus' candidate drug products, the timing and reporting of results from preclinical studies and clinical trials evaluating Amicus' candidate drug products and the projected cash position for the Company. Words such as, but not limited to, "look forward to," "believe," "expect," "anticipate," "estimate," "intend," "potential," "plan," "targets," "likely," "may," "will," "would," "should" and "could," and similar expressions or words identify forward-looking statements. Such forward-looking statements are based upon current expectations that involve risks, changes in circumstances, assumptions and uncertainties. The inclusion of forward-looking statements should not be regarded as a representation by Amicus that any of its plans will be achieved. Any or all of the forward-looking statements in this press release may turn out to be wrong. They can be affected by inaccurate assumptions Amicus might make or by known or unknown risks and uncertainties. For example, with respect to statements regarding the goals, progress, timing and outcomes of discussions with regulatory authorities and the potential goals, progress, timing and results of preclinical studies and clinical trials, actual results may differ materially from those set forth in this release due to the risks and uncertainties inherent in the business of Amicus, including, without limitation: the potential that results of clinical or pre-clinical studies indicate that the product candidates are unsafe or ineffective; the potential that it may be difficult to enroll patients in our clinical trials; the potential that regulatory authorities may not grant or may delay approval for our product candidates; the potential that preclinical and clinical studies could be delayed because we identify serious side effects or other safety issues; the potential that we will need additional funding to complete all of our studies and, our dependence on third parties in the conduct of our clinical studies. Further, the results of earlier preclinical studies and/or clinical trials may not be predictive of future results. With respect to statements regarding projections of the Company's cash position, actual results may differ based on market factors and the Company's ability to execute its operational and budget plans. In addition, all forward looking statements are subject to other risks detailed in our Annual Report on Form 10-K for the year ended December 31, 2013. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, and Amicus undertakes no obligation to revise or update this news release to reflect events or circumstances after the date hereof. This caution is made under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995.



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