ORLANDO, Fla. and CRANBURY, N.J., Feb. 10, 2015 (GLOBE NEWSWIRE) -- Amicus Therapeutics FOLD, a biopharmaceutical company at the forefront of therapies for rare and orphan diseases, today announced positive data on pre-specified patient reported outcomes from both of its Phase 3 studies of the oral small molecule pharmacological chaperone migalastat HCl ("migalastat") for Fabry disease at WORLDSymposium™ 2015 in Orlando, Florida.
Amicus previously reported positive Phase 3 data in both treatment naïve (Study 011, or FACETS) and enzyme replacement therapy (ERT) switch patients (Study 012, or ATTRACT). Results from these studies have shown that treatment with migalastat has resulted in reductions in disease substrate, stability of kidney function and improvement in a key cardiac parameter (left ventricular mass index, or LVMi) in patients with amenable mutations. Pre-specified secondary and tertiary endpoints on patient-reported outcome measures from both Phase 3 studies are being reported for the first time at WORLDSymposium™ 2015.
John F. Crowley, Chairman and Chief Executive Officer of Amicus Therapeutics, Inc., stated, "We are pleased to present compelling new data at WORLDSymposium on patient-reported outcomes on gastrointestinal symptoms, pain, and quality of life from our Phase 3 studies. In addition to the previously reported migalastat Phase 3 data, it was also important to assess the impact of migalastat on some of the most commonly reported symptoms which can severely impact quality of life for people living with Fabry disease. These positive results shown for the first time today in both naïve and ERT switch patients add to the totality of the data that suggest migalastat could be an important new therapy in the treatment of Fabry disease. These data also continue to show the positive effects for patients, owing we believe to migalastat's novel mechanism of action in all key organs and tissues of disease. We continue to move forward rapidly to seek regulatory approval."
Improvements in Gastrointestinal Symptoms Observed in Phase 3 Study 011 (FACETS)
A poster1 at WORLDSymposium described improvements in gastrointestinal symptoms observed in the Phase 3 Study 011 (FACETS) in treatment naïve Fabry patients with amenable mutations. There was a significant decrease in diarrhea (unadjusted p=0.03) in patients treated with migalastat versus placebo during the 6-month double-blind phase (Stage 1). After 18-24 months of treatment with migalastat, significant improvements in diarrhea and indigestion were observed in addition to favorable trends in reflux and constipation.
Raphael Schiffmann, M.D., M.H.Sc., an investigator with the Institute of Metabolic Disease, Baylor Research Institute, Dallas, TX, stated, "Gastrointestinal symptoms are among the most frequently reported and debilitating symptoms among Fabry patients and may not be adequately controlled by current standard of care. As an investigator in clinical studies, I am pleased when improvements in diarrhea and reflux are persistent and durable."
Gastrointestinal symptoms were assessed in 50 subjects with amenable mutations (28 on migalastat, 22 on placebo) using the Gastrointestinal Symptoms Rating Scale (GSRS), a validated instrument of 15 items that includes 5 domains (diarrhea, reflex, indigestion, abdominal pain and constipation).
Stability in Measures of Pain and Quality of Life Observed in Phase 3 Study 012 (ATTRACT)
Patient-reported outcome measures of pain and quality of life from the Phase 3 Study 012 (ATTRACT) in ERT switch patients were described as part of a poster2 and presentation at WORLDSymposium™ 2015. Measures of pain and quality of life from the Brief Pain Inventory (BPI) and Short Form 36 (SF36) remained stable when patients switched from ERT to migalastat.
About Study 011 (FACETS)
Study 011 was a Phase 3 study designed to measure the reduction of disease substrate (globotriaosylceramide, or GL-3) following treatment with migalastat in Fabry patients with amenable mutations. The study also measured clinical outcomes, including renal function and LVMi, as secondary endpoints.The 24-month study began with a 6-month double-blind, placebo-controlled treatment period, after which all patients were treated with migalastat for a 6-month open-label follow-up period and a subsequent 12-month open-label extension phase.
Fabry patients enrolled in Study 011 were naïve to treatment or had not received ERT for at least 6 months prior to study entry. Upon completion, patients were eligible to roll over into a separate extension Study (Study 041) to continue migalastat.
About Study 012 (ATTRACT)
Study 012 was a Phase 3, open-label study that compared oral migalastat to standard-of-care ERTs for Fabry disease (Fabrazyme® and Replagal®). 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.
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. Secondary outcome measures included LVMi, as well as a composite of Fabry-associated clinical events (i.e. renal, cardiac, or cerebrovascular).
About GLP HEK-Amenable Mutations
Amenable mutations are 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. All patients enrolled in Study 011 and Study 012 had amenable mutations in the clinical trial HEK assay available at study initiation ("clinical trial assay"). Following the completion of enrollment, a GLP HEK assay was developed with a third party to measure the criteria for amenability with more quality control and rigor. However, approximately 10% of mutations in the HEK database switched categorization between "amenable" and "non-amenable" when moving from the clinical trial assay to the GLP HEK assay. Therefore there were changes in categorization from amenable to non-amenable in 17 patients in Study 011, and in 4 patients in Study 012.
Overall based on results from mutations tested in the GLP HEK assay, Amicus continues to believe that approximately 30% to 50% of the Fabry population have mutations that are amenable to migalastat.
About Amicus Therapeutics
Amicus Therapeutics FOLD is a biopharmaceutical company at the forefront of therapies for rare and orphan diseases. The Company is developing novel, first-in-class treatments for a broad range of human genetic diseases, with a focus on delivering new benefits to individuals with lysosomal storage diseases. Amicus' lead programs in development include the small molecule pharmacological chaperone migalastat as a monotherapy for Fabry disease, as well as next-generation enzyme replacement therapy (ERT) products for Fabry disease, Pompe disease, and MPS-1.
Forward-Looking Statements
This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 relating to preclinical and clinical development of Amicus' candidate drug products, the timing and reporting of results from preclinical studies and clinical trials evaluating Amicus' candidate drug products and the projected cash position for the Company. Words such as, but not limited to, "look forward to," "believe," "expect," "anticipate," "estimate," "intend," "potential," "plan," "targets," "likely," "may," "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 preclinical studies and 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. With respect to statements regarding projections of the Company's cash position, actual results may differ based on market factors and the Company's ability to execute its operational and budget plans. In addition, all forward looking statements are subject to other risks detailed in our Annual Report on Form 10-K for the year ended December 31, 2013. 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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