Kidney Interstitial Capillary GL-3 Results for 60-Week Treatment on Migalastat HCl Presented at
Pharmacodynamic Markers Indicate Stable Renal Function in Patients With Amenable Mutations
GL-3 in Renal Peritubular Capillary Cells (PTCs, or Interstitial Capillaries)
GL-3 is the lipid substrate that accumulates in tissues affected by Fabry disease, including the kidney. GL-3 inclusions in PTCs - also referred to as interstitial capillaries - are measured by histology from kidney biopsies. Reduction of GL-3 in renal PTCs previously supported conditional approval of enzyme replacement therapy (ERT) for Fabry disease by the
Previous scientific presentations2 highlighted changes in interstitial capillary GL-3 from baseline to various time points in initial Phase 2 studies (Studies 202-204). Changes in interstitial capillary GL-3 from baseline (in Studies 202-204) to follow-up (Study 205) were presented for the first time at ASN 2012. Pathologists blinded to biopsy sequence assessed a total of 8 evaluable paired kidney biopsies by histology using the published, quantitative Barisoni Lipid Inclusion Scoring System (BLISS)3 by virtual microscopy.
Estimated glomerular filtration rate (eGFR) remained stable. In 9 male evaluable patients, decreases in proteinuria from baseline were observed in 8 patients with amenable mutations, with an increase reported in 1 non-amenable patient.
|About The Phase 2 and Phase 2 Extension Studies|
|Phase 2 Protocols Represented in Study 205 (n = 23)|
# in Study
|Study 201 (n=9 males)||12||25, 100 and 250 mg twice-daily (BID) then 50 mg once-daily (QD)||84||No||6||6|
|Study 202 (n=4 males)||12||150 mg, every-other-day (QOD)***||36||Yes||3||2|
|Study 203 (n=5 males)||24||150 mg QOD***||24||Yes||5||3|
|Study 204 (n=9 females)||12||50, 150***, or 250 mg QOD||36||Yes||9||5|
|*Per protocols, no kidney biopsies in Study 201; kidney biopsies in Studies 202-204 at baseline, after primary treatment period, and after extension period|
|**Retrospectively identified as amenable to migalastat HCl in a cell-based assay|
|***Dose selected for Phase 3 studies (150 mg QOD)|
Study 205 is an open-label extension study to investigate the long-term safety, tolerability and pharmacodynamics of migalastat HCl that enrolled 23 patients with Fabry disease who completed four open-label Phase 2 studies (Study 201, -202, -203 and -204) to evaluate the safety and tolerability of various doses and dose regimens of oral migalastat HCl. In addition to safety and tolerability, Study 205 is evaluating globotriaosylceramide (GL-3) in interstitial capillaries, an important biomarker for Fabry disease, as well as kidney function as measured by estimated glomerular filtration rate (eGFR) and proteinuria.
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
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 amenable mutations. Study 011 is a placebo-controlled study intended primarily to support U.S. registration, and Study 012 is comparing open-label 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. Migalastat HCl co-administered with ERT is in Phase 2 (Study 013) and migalastat HCl co-formulated with
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.
2. Shiffmann, et al., LDN WORLD 2011, Long-Term Safety, Tolerability, and Assessments of Renal Function in Adult Fabry Patients Receiving Treatment with AT1001 (Migalastat Hydrochloride), a Pharmacological Chaperone
Giugliani, et al., LDN WORLD 2012, Oral Migalastat HCL (AT1001/GR181314A) as an Investigational Therapy Evaluated in Females with Fabry Disease
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," "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 Annual Report on Form 10-Q for the quarter ended
Sara Pellegrinospellegrino@amicusrx.com (609) 662-5044
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