Rare Disease Report

"Today is a Great Day for the Fabry Community"

AUGUST 20, 2014
James Radke

This morning, Amicus Therapeutics announced positive  results from their phase 3 clinical trial studying the efficacy and safety of migalastat in Fabry disease patients with amenable mutations.

The study (Study 012) compared oral migalastat to standard-of-care enzyme replacement therapies (ERTs) for Fabry disease (Fabrazyme and Replagal) in 56 Fabry disease patients with amenable mutations (of 60 total patients). All patients had been treated with ERT for a minimum of 12 months prior to study entry. 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.

In this study, ‘amenable mutations’ were 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.

In a press release, Amicus posted the following study summary:
  • 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.

(data presented during Amicus webcast presented Aug 20, 2014 at http://ir.amicustherapeutics.com/events.cfm)

The press release also includes many quotes from Amicus as well as clinical and advocacy representatives.

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 added, "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 also stated , "Given the choice, I would use migalastat over ERT for the treatment of Fabry patients with amenable mutations."

Jack Johnson, Founder and Executive Director, Fabry Support & Information Group said, "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," adding,  "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."

Fabry Disease

Fabry disease is an X-linked lysosomal storage disorder that leads to excessive deposition of glycosphingolipids throughout the body. Skin, eye, kidney, heart, brain, and peripheral nervous system are highly vulnerable. Fabry disease is often difficult to diagnose since signs and symptoms are often nonspecific. For example, common symptoms may be fatigue, neuropathy (in particular, burning extremity pain), cerebrovascular effects leading to an increased risk of stroke, tinnitus (ringing in the ears), vertigo, nausea, inability to gain weight, chemical imbalances, diarrhea etc. 

Symptoms do appear in childhood but often go undiagnosed for several years. As the disease progressive, most patients with Fabry disease die in their fourth or fifth decade due to complications arising from renal or cardiovascular problems.

Currently, Genzyme’s Fabrazyme is the only approved treatment for Fabry disease in the United States.  Fabrazyme is also approved in Europe and elsewhere, as is Shire’s Replagal.

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