Amicus Therapeutics
Jul 2, 2012

Amicus Therapeutics Announces Publication of BLISS Quantitative Histology Method in Archives of Pathology & Laboratory Medicine

Developed for Phase 3 Clinical Study of Migalastat HCl for Fabry Disease to Improve Sensitivity, Accuracy and Reproducibility of Renal Histology Assessment

CRANBURY, N.J., July 2, 2012 (GLOBE NEWSWIRE) -- Amicus Therapeutics, Inc. (Nasdaq:FOLD), a biopharmaceutical company at the forefront of therapies for rare and orphan diseases, today announced that a manuscript describing the Barisoni Lipid Inclusion Scoring System (BLISS) has been published in the July 2012 issue of Archives of Pathology & Laboratory Medicine. The manuscript titled, "A Novel, Quantitative Method to Evaluate GL-3 Inclusions in Renal Peritubular Capillaries by Virtual Microscopy in Patients with Fabry Disease,"1 is currently available online.

BLISS improves the ability to detect and quantify changes in globotriaosylceramide (GL-3) peritubular capillary (PTC) inclusions - also referred to as interstitial capillaries - in females and males with Fabry disease. GL-3 is the lipid substrate that accumulates in tissues affected by Fabry disease, including the kidney. BLISS was developed by Dr. Laura Barisoni while she was an Associate Professor in Pathology and Medicine at the New York University School of Medicine, in collaboration with Amicus. Dr. Barisoni is currently a Voluntary Associate Professor in Pathology at the University of Miami.

In a Phase 3 study (Study 011) intended for U.S. registration of migalastat HCl monotherapy for Fabry disease, BLISS with virtual microscopy will be utilized for the histological evaluation of interstitial capillary GL-3 in kidney biopsies, the primary endpoint. Migalastat HCl is an oral investigational pharmacological chaperone for Fabry disease being developed by Amicus in collaboration with GlaxoSmithKline (GSK).

Previous pivotal studies of enzyme replacement therapy (ERT) for Fabry disease used a semi-quantitative approach with conventional light microscopy. Pathologist readers manually searched for and categorically scored PTC GL-3 (0, 1, 2, or 3) within the same histological sections, but not necessarily in the same PTCs. A more sensitive methodology was needed to more accurately and reliably quantify GL-3 inclusions, and to assess response to treatment, particularly in patients who have lower amounts of GL-3.

Published Results

The study published by Dr. Barisoni and colleagues compared BLISS to the previously reported semi-quantitative scoring method. Intra- and inter-reader variability was also assessed using BLISS in combination with virtual microscopy (BLISS-VM) versus conventional light microscopy (BLISS-LM). The novel BLISS-VM protocol was created by the pathology team composed of Dr. Barisoni; Dr. Charles Jennette, Professor and Chair at the University of North Carolina-Chapel Hill; and Dr. Robert Colvin, Professor in Pathology at the Massachusetts General Hospital.

Pre-treatment kidney biopsies were scored from 17 patients (eight males and nine females) enrolled in three Phase 2 studies of migalastat HCl. Results demonstrated that BLISS is a more sensitive scoring system to measure GL-3 inclusions in PTCs compared to the semi-quantitative methodology. The addition of virtual microscopy further improved accuracy and reproducibility of BLISS, reducing intra- and inter-reader variability. BLISS-VM used one pathologist annotator to identify PTCs on a scanned digital slide image, and different pathologist readers to score the total number of GL-3 inclusions in each PTC identified by the annotator. The annotation step ensures that both readers are scoring the same PTCs. Results are digitally recorded as each PTC is scored to prevent double counting. The scored digital images also provide a permanent and retrievable record for clinical studies and submission to regulatory authorities.

Dr. Barisoni stated, "We developed BLISS as a novel quantitative methodology to detect GL-3 in both male and female Fabry patients. Our study showed that BLISS was able to detect GL-3 inclusions that were missed by the semi-quantitative scoring method. While the traditional semi-quantitative methodology can measure GL-3 inclusions in patients with a high level of GL-3 storage, a large percentage of Fabry patients have some residual enzyme activity and fewer GL-3 inclusions. In addition, innovations in digital imaging have made it possible to incorporate virtual microscopy to address several limitations of conventional light-based microscopy."

Drs. Barisoni, Jennette, and Colvin will utilize BLISS-VM to score the kidney biopsies of Fabry patients in Study 011. Amicus and GlaxoSmithKline (GSK) are on track to report results from this study in the third quarter of 2012.

1. Barisoni L.1, Jennette J.C.2, Colvin R.3, Sitaraman S.4, Bragat A.4, Castelli J.4, Boudes P.4, Archives of Pathology & Laboratory Medicine: July 2012, Vol. 136, No. 7, pp. 816-824.

1New York University Langone Medical Center, NY, NY; 2University of North Carolina Medical Center, Chapel Hill NC; 3Massachusetts General Hospital, Boston, MA; 4Amicus Therapeutics, Inc., Cranbury, NJ, USA

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.

About Migalastat HCl

Migalastat HCI is an investigational oral pharmacological chaperone for the treatment of Fabry disease being developed in collaboration with GlaxoSmithKline (GSK). Under the terms of the collaboration, GSK has an exclusive worldwide license to develop, manufacture and commercialize migalastat HCl.

Amicus and GSK are conducting two Phase 3 global registration studies (Study 011 and Study 012) of migalastat HCl monotherapy, along with a Phase 2 study (Study 013) evaluating migalastat co-administered with enzyme replacement therapy (ERT) for the treatment of Fabry disease. 

About Fabry Disease

Fabry disease is an inherited lysosomal storage disease that is currently estimated to affect approximately 5,000 to 10,000 people worldwide. Fabry Disease is 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 a complex lipid called globotriaosylceramide (GL-3). Reduced or absent levels of alpha-Gal A activity leads to the accumulation of GL-3 in the affected tissues, including the central nervous system, heart, kidneys, 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 disorders and stroke.

Forward Looking Statements

Statements in this press release concerning Amicus' future expectations, plans and prospects, including, without limitation, statements regarding the proposed public offering, constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements due to various risks, uncertainties and important factors, including those set forth in the "Risk Factors" section in our Annual Report on Form 10-K for the fiscal year ended December 31, 2011 filed with the Securities and Exchange Commission, any of which could cause our actual results to differ from those contained in the forward-looking statements. 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.


CONTACT: Amicus Therapeutics

         Sara Pellegrino

         (609) 662-5044

Source: Amicus Therapeutics, Inc.

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