Amicus Therapeutics Announces Additional Preliminary Results From Ongoing Phase 2 Chaperone-Enzyme Replacement Therapy (ERT) Study for Fabry Disease

Drug-Drug Interaction Study Evaluating Pharmacokinetics and Safety Presented at ASHG

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| Source: Amicus Therapeutics, Inc.

CRANBURY, N.J., Nov. 8, 2012 (GLOBE NEWSWIRE) -- Amicus Therapeutics (Nasdaq:FOLD), today announced additional preliminary results from an open-label Phase 2 drug-drug interaction study (Study 013) to evaluate a single oral dose of migalastat HCl (150 mg or 450 mg) co-administered with enzyme replacement therapy (ERT) in males with Fabry disease. In a poster at the American Society of Human Genetics (ASHG) Annual Meeting Dr. David G. Warnock, University of Alabama-Birmingham, presented results from all 12 patients in the migalastat HCl 150 mg dose group.

Amicus, in collaboration with GlaxoSmithKline (GSK), is developing the investigational pharmacological chaperone migalastat HCl as a monotherapy and in combination with ERT for the treatment of Fabry disease. When co-administered with ERT, migalastat HCl binds to and stabilizes infused enzyme in the circulation.

Dr. Warnock said, "Migalastat HCl 150 mg co-administered with two different doses of Fabrazyme, as well as one dose of Replagal, appeared to increase enzyme activity compared to each of these ERTs alone. The use of a pharmacological chaperone to maintain infused alpha Gal-A enzymes in optimally active form represents a potential approach to managing ERT outcomes in patients with Fabry disease."

Results were presented for a total of 12 patients who received migalastat HCl 150 mg co-administered with ERT (Fabrazyme in 8 patients and Replagal in 4 patients). Each patient received their current dose and regimen of ERT at one infusion. A single oral dose of migalastat HCl 150 mg was co-administered two hours prior to the next infusion of the same ERT at the same dose and regimen. Due to the Fabrazyme supply difficulties during enrollment, 5 subjects had been receiving 0.5 mg/kg Fabrazyme infused every two weeks and 3 subjects had been receiving 1.0 mg/kg infused every four weeks. Four subjects were receiving Replagal 0.2 mg/kg every two weeks.

Preliminary Results - Migalastat HCl 150 mg Co-Administered with ERT (Fabrazyme and Replagal) (n=12)

  • To date no serious adverse events or adverse events in this study have been deemed related to migalastat HCl when co-administered with ERT. All other treatment emergent adverse events were considered by the investigators unrelated to study drug, and except for one incident of severe paresthesia, were mild in intensity.
  • Increases in levels of active enzyme in plasma in 12 out of 12 patients demonstrated a drug-drug interaction between migalastat HCl 150 mg and Fabrazyme, and between migalastat HCl 150 mg and Replagal. Increased levels of active enzyme were observed in skin biopsy samples on day 2 and, to a lesser extent, on day 7. The clinical significance of these results are not yet known.
  • Further investigations are being conducted with migalastat HCl 450 mg co-administered with Fabrazyme and Replagal. Updated results are anticipated in the first quarter 2013.
 
Alpha-Gal A Levels of Active Enzyme in Plasma Area Under the Curve (AUC)
Migalastat HCl + ERT vs. ERT Alone
No. of
Patients
Migalastat HCl Dose ERT Mean Fold-Increase vs. ERT Alone (Range)
4 150 mg Replagal 0.2 mg/kg 4.4 (3.2 to 5.0)
5 150 mg Fabrazyme 0.5 mg/kg 3.0 (2.0 to 4.2)
3 150 mg Fabrazyme 1.0 mg/kg 2.0 (1.6 to 2.2)
 
Alpha-Gal A Levels of Active Enzyme in Skin at Days 2 and 7
Migalastat HCl + ERT vs. ERT Alone
No. of
Patients
Migalastat
HCl Dose
ERT Mean Fold-Increase vs. ERT
Alone at Day 2 (Range)
Mean Fold-Increase vs. ERT
Alone at Day 7 (Range)
4 150 mg Replagal 0.2 mg/kg 1.8 (1.4 to 2.3) 1.4 (1.1 to 1.8)
5 150 mg Fabrazyme 0.5 mg/kg 2.6 (1.1 to 3.9) 1.4 (0.7 to 2.8)
3 150 mg Fabrazyme 1.0 mg/kg 1.9 (1.6 to 2.1) 1.4 (1.2 to 1.7)

John F. Crowley, Chairman and Chief Executive Officer of Amicus Therapeutics said, "We believe that this is a continued positive step forward in evaluating this core aspect of our Amicus technology. These updated results from Study 013 support further investigation into the safety and efficacy of chaperone-ERT co-administration. Early next year we look forward to having the final results of this study."

About Study 013

Study 013 is an open-label Phase 2 drug-drug interaction study to evaluate the safety and pharmacokinetic (PK) effects a single oral dose of migalastat HCl (150 mg or 450 mg) co-administered with ERT (Fabrazyme® or Replagal®). Study 013 completed enrollment of 23 males with Fabry disease who are currently on ERT. Each patient receives their regular dose and regimen of ERT. A single oral dose of migalastat HCl is co-administered 2 hours prior to the next ERT infusion.

Enzyme activity is being measured in plasma (total area under the curve, or AUC) during each infusion and in tissue (skin) following each infusion. In published preclinical studies1 migalastat HCl co-administered with ERT in Fabry knock-out mice increased active enzyme in plasma and enzyme uptake into skin, which led to further reductions in globotriaosylceramide (GL-3) compared to ERT alone. For people living with Fabry disease, deficient alpha-Gal A enzyme activity leads to the accumulation of globotriaosylceramide (GL-3) in tissues affected by disease, including the kidney, heart and skin.

About Migalastat HCl

Amicus in collaboration with GlaxoSmithKline (GSK) is developing the investigational pharmacological chaperone migalastat HCl for the treatment of Fabry disease. Amicus has commercial rights to all Fabry products in the United States and GSK has commercial rights to all of these products in the rest of world.

As a monotherapy, migalastat HCl is designed to bind to and stabilize, or "chaperone" a patient's own alpha-galactosidase A (alpha-Gal A) enzyme in patients with genetic mutations that are amenable to this chaperone in a cell-based assay. Migalastat HCl monotherapy is in Phase 3 development (Study 011 and Study 012) for Fabry patients with genetic mutations that are amenable to this chaperone monotherapy in a cell-based assay. Study 011 is a placebo-controlled study intended primarily to support U.S. registration, and Study 012 compares migalastat HCl to ERT to primarily support global registration.

For patients currently receiving ERT for Fabry disease, migalastat HCl in combination with ERT may improve ERT outcomes by keeping the infused alpha-Gal A enzyme in its properly folded and active form.

Migalastat HCl co-administered with ERT is in Phase 2 (Study 013) and migalastat HCl co-formulated with JCR Pharmaceutical Co. Ltd's proprietary investigational ERT (JR-051, recombinant human alpha-Gal A enzyme) is in preclinical development.

About Fabry Disease

Fabry disease is an inherited lysosomal storage disorder caused by deficiency of an enzyme called alpha-galactosidase A (alpha-Gal A). The role of alpha-Gal A within the body is to break down specific lipids in lysosomes, including globotriaosylceramide (GL-3, also known as Gb3). Lipids that can be degraded by the action of α-Gal are called "substrates" of the enzyme. Reduced or absent levels of alpha-Gal A activity leads to the accumulation of GL-3 in the affected tissues, including the kidneys, heart, central nervous system, and skin. This accumulation of GL-3 is believed to cause the various symptoms of Fabry disease, including pain, kidney failure, and increased risk of heart attack and stroke.

It is currently estimated that Fabry disease affects approximately 5,000 to 10,000 people worldwide. However, several literature reports suggest that Fabry disease may be significantly under diagnosed, and the prevalence of the disease may be much higher.

About Amicus Therapeutics

Amicus Therapeutics (Nasdaq:FOLD) is a biopharmaceutical company at the forefront of developing therapies for rare diseases. The Company is developing orally-administered, small molecule drugs called pharmacological chaperones, a novel, first-in-class approach to treating a broad range of human genetic diseases. Amicus' late-stage programs for lysosomal storage disorders include migalastat HCl monotherapy in Phase 3 for Fabry disease; migalastat HCl co-administered with enzyme replacement therapy (ERT) in Phase 2 for Fabry disease; and AT2220 co-administered with ERT in Phase 2 for Pompe disease.

Forward-Looking Statements

This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 relating to clinical development of Amicus' candidate drug products and the timing and reporting of results from clinical trials evaluating Amicus' candidate drug products. Words such as, but not limited to, "look forward to," "believe," "expect," "anticipate," "estimate," "intend," "plan," "targets," "likely," "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 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. In addition, all forward looking statements are subject to other risks detailed in our Quarterly Report on Form 10-Q for the quarter ended June 30, 2012. 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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