Amicus Therapeutics Presents Additional Results From Phase 2 Chaperone-Enzyme Replacement Therapy (ERT) Study For Fabry Disease At LDN World Symposium

CRANBURY, N.J. and ORLANDO, Fla., Feb. 13, 2013 (GLOBE NEWSWIRE) -- Amicus Therapeutics (Nasdaq:FOLD), today announced further 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 prior to enzyme replacement therapy (ERT) in males with Fabry disease. Preliminary results were announced during 2012. Results for the migalastat HCl 450 mg dose group are being presented for the first time in a poster 1 at the Lysosomal Disease Network WORLD Symposium ( LDN WORLD).

Dr. David G. Warnock, University of Alabama-Birmingham, stated, "When co-administered with ERT, both doses of migalastat HCl appeared to increase enzyme activity compared to Fabrazyme and Replagal alone in this study. We believe that these results support further clinical studies in Fabry patients to investigate the use of a pharmacological chaperone to maintain infused alpha Gal-A enzymes in optimally active form through this chaperone-ERT combination approach."

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.

Migalastat HCl (150 mg and 450 mg) Co-Administered with ERT (Fabrazyme and Replagal)

Each patient in Study 013 received their current dose and regimen of ERT (Fabrazyme® or Replagal®, infused alpha-Gal A enzymes) at one infusion. A single oral dose of migalastat HCl (150 mg or 450 mg) was co-administered 2 hours prior to the next infusion of the same ERT at the same dose and regimen. Among 20 total males who enrolled, 3 opted to participate in the migalastat 150 mg and then again in the 450 mg treatment arms.
  • Safety: finalized safety data are expected in 2Q13. As currently evaluated, 2 serious adverse events (SAEs) occurred in one patient (transient ischemic attack and hospitalization for acute pain and acroparesthesia due to Fabry disease) and were considered by the investigator to be unrelated to migalastat HCl when co-administered with ERT. Of the remaining treatment emergent adverse events the majority were unrelated to study drug.
  • Active enzyme in plasma: active alpha-Gal A enzyme levels were measured in plasma (total area under the curve, or AUC) during and after each infusion. Following co-administration, active enzyme levels in plasma increased in 22 out of 23 instances and were unchanged in 1 instance compared to ERT alone. These PK results demonstrated a drug-drug interaction between both doses of migalastat HCl and both ERTs.
  • Enzyme uptake into skin: alpha-Gal A enzyme levels were also measured in skin following each infusion. Increased levels of alpha-Gal A enzyme measured in skin biopsy samples on day 2 and, to a lesser extent, on day 7, showed increased enzyme uptake into tissue compared to ERT alone. This exploratory assessment showed that the greatest increases in active alpha-Gal A enzyme levels were observed following migalastat HCl 450 mg co-administered with ERT. 
  Alpha-Gal A Levels of Active Enzyme 
  Mean-Fold Increase in Plasma Area Under Curve (AUC) vs. ERT Alone (Range) Mean-Fold Increase in Skin at Day 2 vs. ERT Alone (Range) Mean-Fold Increase in Skin at Day 7 vs. ERT Alone (Range)
Migalastat HCl 150 mg + Replagal 0.2 mg/kg (n = 4) 4.3 (3.2 to 5.0) 1.8 (1.4 to 2.3) 1.4 (1.1 to 1.8)
Migalastat HCl 150 mg + Fabrazyme 0.5 mg/kg (n = 5)* 3.0 (2.0 to 4.2) 2.6 (1.1 to 3.9) 1.4 (0.7 to 2.8)
Migalastat HCl 150 mg + Fabrazyme 1.0 mg/kg (n = 3) 2.0 (1.6 to 2.2) 1.9 (1.6 to 2.1) 1.4 (1.2 to 1.7)
Migalastat HCl 450 mg + Replagal 0.2 mg/kg (n = 4) 3.1 (2.3 to 5.0) 2.3 (1.6 to 3.7) 2.1 (1.0 to 2.8)
Migalastat HCl 450 mg + Fabrazyme 0.5 mg/kg (n = 1)* 2.4 3.7 1.9
Migalastat HCl 450 mg + Fabrazyme 1.0 mg/kg (n = 6) 2.0 (1.0 to 3.2) 1.8 (1.0 to 2.5) 1.5 (0.6 to 3.3)

* Due to Fabrazyme supply difficulties during enrollment, subjects had been receiving 0.5 mg/kg Fabrazyme infused every two weeks

John F. Crowley, Chairman and Chief Executive Officer of Amicus Therapeutics said, "Study 013 was the first clinical study to investigate the chaperone-ERT combination approach. This study has been a major catalyst for our further development of chaperone-ERT combinations across the lysosomal storage diseases, including chaperones co-administered with marketed ERTs as well as proprietary chaperone-ERT co-formulated products in preclinical development as next-generation ERTs."

In addition to chaperone-ERT co-administration in Fabry disease, Amicus and GSK are developing migalastat HCl co-formulated with JCR Pharmaceutical Co. Ltd's proprietary investigational ERT (JR-051, recombinant human alpha-Gal A enzyme). This chaperone-ERT co-formulated product has the potential to enter the clinic in late-2013 or early 2014.

Conference Call and Webcast

John F. Crowley, Chairman and Chief Executive Officer, and members of the Amicus executive team will host a conference call and live audio/visual webcast on Friday, February 15, 2013 at 11:30am ET to discuss the data from several programs presented at LDN WORLD. Interested participants and investors may access the conference call at 11:30 a.m. ET by dialing 877-303-5859 (U.S./Canada) or 678-224-7784 (international). A live audio webcast can also be accessed via the Investors section of the Amicus Therapeutics corporate web site at http://ir.amicustherapeutics.com/events.cfm , and will be archived for 30 days. The slide presentation for the conference call/webcast will also be available at http://ir.amicustherapeutics.com/events.cfm . Web participants are encouraged to go to the web site 15 minutes prior to the start of the call to register, download and install any necessary software. A telephonic replay of the call will be available for seven days beginning at 2:30 p.m. ET on February 15, 2013. Access numbers for this replay are 855-859-2056 (U.S./Canada) and 404-537-3406 (international); participant code 97505816.

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 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.

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 thereby allowing more active enzyme to reach tissues. 2 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.

1. Bichet, 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, LDN WORLD 2012

2. Benjamin, et al., Molecular Therapy: April 2012, Vol. 20, No. 4, pp. 717–726.

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," "may," "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.

FOLD–G

CONTACT: Investors/Media:         Sara Pellegrino         spellegrino@amicusrx.com         (609) 662-5044                  Media:         Dan Budwick         (973) 271-6085         dan@purecommunicationsinc.com

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