Amicus Therapeutics Announces Positive Phase 3 Data From Fabry Monotherapy Study 012

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Migalastat Successfully Meets Both Co-Primary Endpoints of Comparability to Enzyme Replacement Therapy (ERT) on Both Key Measures of Kidney Function

Comparability to ERT Also Demonstrated in Important Fabry Disease Biomarker, Plasma Lyso-Gb3

Proceeding with Centralized Procedure for European MAA Submission

August 20th, 2014

Amicus Therapeutics (Nasdaq:FOLD), a biopharmaceutical company at the forefront of therapies for rare and orphan diseases, today announced positive 18-month data from its second Phase 3 study (Study 012) of the oral small molecule chaperone migalastat HCl (“migalastat”) in Fabry patients with amenable mutations. Detailed results of this second Phase 3 monotherapy study are available in a slide presentation that were shared by the Amicus management team on a conference call on the 20th of August 2014 at 8am.

Study 012 compared oral migalastat to standard-of-care enzyme replacement therapies (ERTs) for Fabry disease (Fabrazyme® and Replagal®). 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. 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. Among the 60 patients enrolled, 56 (34 in the migalastat group and 22 in the ERT group) had amenable mutations in a GLP-validated human embryonic kidney (HEK) cell-based in vitro assay (“GLP HEK-amenable”). The statistical analysis plan pre-specified that all efficacy measures would be based on the results from patients with GLP HEK-amenable mutations.

Summary of Study 012 18-Month Results

  • Migalastat had a comparable effect to ERT on patients’ kidney function as measured by the change in eGFR and mGFR.
  • Levels of plasma lyso-Gb3, an important biomarker of disease, remained low and stable in patients with amenable mutations who switched from ERT to migalastat.
  • Migalastat was generally safe and well-tolerated.
  • Of 48 patients with GLP HEK-amenable mutations who completed Study 012, 46 (96%) elected to continue with the 12-month treatment extension and 45 remain on migalastat today as their only treatment for Fabry disease.

John F. Crowley, Chairman and Chief Executive Officer of Amicus Therapeutics, Inc., stated, “We believe that this multi-year study unequivocally demonstrates that a Fabry patient on ERT with an amenable mutation can switch safely and effectively from ERT to migalastat to treat their Fabry disease. Today is a great day for the Fabry community and for Amicus. This study was resoundingly positive and met our pre-defined criteria for success in terms of the co-primary endpoints of kidney function. These results clearly show that migalastat is comparable to ERT in slowing the progression of Fabry disease and continues to demonstrate a favorable safety profile. With every-other-day oral administration and a differentiated mechanism of action, migalastat may offer significant advantages for patients without the need for bi-weekly infusions with ERT. Combined with our previous Phase 3 results from Study 011, we have a compelling and consistent data set from both treatment-naïve and ERT-experienced patients. Given these results and the great need for new and effective medicines, we plan to work with European and U.S. regulators to determine the fastest way to get migalastat approved for all amenable Fabry patients.”

Raphael Schiffmann, M.D., M.H.Sc., an investigator with the Institute of Metabolic Disease, Baylor Research Institute, Dallas, TX stated, “I believe the results from Study 012 show a positive treatment effect of migalastat in Fabry patients with amenable mutations. The stabilization of renal function and the maintenance of substrate levels as measured by lyso-Gb3 provide further clinical evidence that supports my experience over the last eight years in treating Fabry patients with migalastat in various clinical studies. When combined with the favorable safety profile, the totality of the data from Study 012 and Study 011 indicate that migalastat should become an important new oral treatment option for Fabry patients.”

Dr. Schiffmann added, “Given the choice, I would use migalastat over ERT for the treatment of Fabry patients with amenable mutations.”

Study 012 Kidney Function Data in GLP HEK-Amenable Patients

Among patients with GLP HEK-amenable mutations in Study 012, kidney function was comparable to ERT over 18 months following treatment with migalastat. Decline in kidney function is a key cause of mortality in patients with Fabry disease.

Overlap of
and ERT
Mean Values ± SEM Median Values
(means) (means) Migalastat group
ERT group
Migalastat group
ERT group
100% +0.63  -0.40 ± 0.93  -1.03± 1.29  -1.29 -0.87
100% -1.11  -4.35 ± 1.64  -3.24 ± 2.27 -3.23 -3.57

As pre-specified in the final statistical analysis plan, the co-primary outcome measures of efficacy in Study 012 were the descriptive assessments of comparability of the mean annualized change in eGFR and mGFR for migalastat and ERT. Both eGFR and mGFR are considered important measures of renal function. Comparability on eGFR and mGFR was defined in two ways:

  • A ≥50% overlap in the confidence intervals between the migalastat and ERT treatment groups; and
  • Whether the mean annualized changes for patients receiving migalastat are within 2.2 mL/min/1.73 m2/yr of patients receiving ERT.

“These data mark an exciting day for the Fabry community and validate our long-term commitment to work in partnership with industry toward our goal of multiple treatment options and improved medicines for all people living with Fabry disease,” saidJack Johnson, Founder and Executive Director, Fabry Support & Information Group. “We await the regulatory agencies’ review of these data, and we are grateful to the many people with Fabry disease, families and volunteers who have committed so much of themselves to help accelerate efforts to bring a more convenient and effective therapy to people living with the disease.”

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