CRANBURY, N.J., June 26, 2012 (GLOBE NEWSWIRE) -- Amicus Therapeutics (FOLD), today announced positive preliminary results from an ongoing Phase 2 open-label drug-drug interaction study (Study 010) to evaluate the safety and pharmacokinetic (PK) effects of the pharmacological chaperone AT2220 (duvoglustat HCl) co-administered with enzyme replacement therapy (ERT) for Pompe disease.
John F. Crowley, Chairman and Chief Executive Officer of Amicus Therapeutics said, “Positive preliminary results from the first two lower dose cohorts in Study 010 further validate our chaperone-ERT combination platform technology. This study represents the second time in which we have seen consistent enhancement of ERT activity with different chaperones co-administered with different ERTs in clinical studies for two different lysosomal storage disorders. It is a great step forward in the development of this Amicus platform technology in Pompe disease and we look forward to additional important data from the remaining two cohorts in this clinical study.”
AT2220 is an investigational oral pharmacological chaperone being developed exclusively by Amicus. Study 010 is investigating four ascending doses of AT2220 co-administered with the ERT alglucosidase alfa (Myozyme(R)/Lumizyme(R)), the first and only treatments approved for Pompe disease. In addition to safety and plasma PK effects, enzyme uptake into muscle tissue is being measured with and without AT2220.
Previous preclinical studies using acid alpha-glucosidase (GAA) knock-out mouse models of Pompe disease demonstrated that AT2220 co-administered with ERT increased the ERT uptake in key tissues of disease, including skeletal muscle and heart. This increased ERT uptake into muscle following AT2220-ERT co-administration corresponded in preclinical studies with greater reductions in muscle glycogen compared to ERT alone. Glycogen is the substrate that accumulates in the lysosomes of muscles in patients with Pompe disease.
Data from Study 010 are currently available for all patients enrolled in Cohorts 1 (n=4) and 2 (n=6), representing the two lowest dose groups of AT2220. Each patient received one infusion of ERT alone, and then a single oral dose of AT2220 just prior to the next ERT infusion. Muscle biopsies were performed seven days following each infusion in all four patients in Cohort 1. Among the six patients in Cohort 2, three had muscle biopsies three days after each infusion and three had muscle biopsies seven days after each infusion.
Preliminary Results - Two Ascending Doses of AT2220 Co-Administered with ERT (n=10)
Safety:
• No drug-related adverse events have been reported to date
• Per the study protocol, an independent data safety monitoring board has reviewed safety data from the first two cohorts and determined that the study should continue into the third dose group (Cohort 3), which is now fully enrolled.
GAA Enzyme Activity in Plasma:
• In Cohort 1, an increase in GAA enzyme activity was seen in 4 out of 4 patients. The increases in activity ranged from 1.2- to 1.6-fold.
• In Cohort 2, an increase in GAA enzyme activity was seen in 6 out of 6 patients. The increases in activity ranged from 1.5- to 1.9-fold.
• Increases in GAA enzyme activity in plasma in 10 out of 10 individuals following co-administration indicate a consistent, positive drug-drug interaction between AT2220 and ERT with the two lowest doses of AT2220, consistent with prior preclinical studies.
• The first two low dose groups provide initial human proof-of-concept that AT2220-ERT co-administration increases the total amount of GAA enzyme activity in plasma.
GAA Enzyme Activity in Muscle:
• In Cohort 1, there was no consistent increase in GAA enzyme activity in the Day 7 muscle biopsies compared to ERT alone.
• In Cohort 2, there were increases in GAA enzyme activity seen in 2 out of 3 patients in the Day 3 muscle biopsies compared to ERT alone. The increases seen were 1.4- and 1.6-fold.
• In Cohort 2, there were increases in GAA enzyme activity seen in 2 out of 3 patients in the Day 7 muscle biopsies compared to ERT alone. The increases seen were 1.1- and 1.6-fold.
• In Cohort 2, the muscle biopsies suggest that more enzyme is taken up into muscle tissue following AT2220 co-administration compared to ERT alone, consistent with prior preclinical experiments.
Pol F. Boudes, MD, Chief Medical Officer of Amicus Therapeutics said, “There is still tremendous unmet need in the Pompe community and a clear desire to improve outcomes with ERT. The Amicus technology has the potential to address complications related to the unfolding and instability of the current Pompe ERT, which may lead to a lack of enzyme potency and activity, and potentially the misdirection of ERT to non-target tissues. We are encouraged by these preliminary results in Study 010 and look forward to evaluating whether the higher doses of AT2220 in Cohorts 3 and 4 may further enhance enzyme activity and ERT uptake into muscle.”
Anticipated Pompe Program Milestones in Second Half of 2012
Third Quarter:
• Initial results from in vitro studies to evaluate the immunogenicity of the Lumizyme ERT, with and without AT2220. These studies which utilize the proprietary EpiScreen(TM) assay from Antitope Ltd. seek to determine if particular human leukocyte antigen (HLA) types are predictive of clinical immunogenicity to Lumizyme, and whether the addition of AT2220 can decrease T-cell response induced by Lumizyme.
• Completion of enrollment in Study 010 with the highest AT2220 dose in Cohort 4.
• Presentation of preclinical results of the direct co-formulation of AT2220 with an ERT. This chaperone-ERT co-formulation is designed to stabilize ERT in the infusion bag, prior to reaching the circulation.
Fourth Quarter:
• Full results from Study 010 (including Cohorts 3 and 4) to be presented at Fall 2012 scientific congress.
• Amicus announcement on plans for the further development of AT2220-ERT co-administration in Pompe disease.
Study 010 Design
Study 010 is a Phase 2 open-label, multi-center study to evaluate the safety and PK effects of four increasing oral doses of AT2220 co-administered with ERT versus ERT alone in individuals with Pompe disease.
The study is enrolling male and female patients who have been on a stable dose and regimen of ERT for at least three months. All patients are given a regularly scheduled ERT infusion. One hour prior to the initiation of the next ERT infusion, subjects receive a single oral dose of AT2220. Plasma GAA activity and protein levels are evaluated during each infusion. Each patient undergoes muscle biopsies three or seven days after each infusion to measure tissue ERT activity with and without the chaperone, as well as to measure the level of AT2220.
More information about Study 010, including patient eligibility, enrollment requirements and study location sites can be obtained by visiting www.clinicaltrials.gov: NCT1380743 or www.pompestudy.com, calling the patient hotline at 855-POMPE-33 (855-766-7333), or e-mailing inquiries to info@pompestudy.com.
About Amicus Therapeutics
Amicus Therapeutics (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 AT2220 for Pompe Disease
AT2220 is an investigational, orally-administered pharmacological chaperone owned exclusively by Amicus. The Company is currently investigating AT2220 (duvoglustat HCl) co-administered with the ERT alglucosidase alfa (Myozyme/Lumizyme) in a Phase 2 study (Study 010) in individuals with Pompe disease.
In parallel with Study 010 Amicus is investigating ERT-related immunogenicity in Pompe disease. Immune responses occur in a majority of Pompe patients receiving alglucosidase alfa infusions1 which have the potential to limit treatment outcomes with ERT. Preclinical results to date suggest that AT2220-ERT co-administration may mitigate ERT-induced immunogenicity by stabilizing the enzyme in its properly folded and active form.
Pompe disease is a lysosomal storage disease characterized by progressive skeletal muscle weakness and respiratory insufficiency. It is caused by a deficiency in GAA activity, which leads to accumulation of glycogen in tissues affected by the disease (primarily muscle). Pompe disease affects an estimated 5,000 to 10,000 individuals worldwide and is clinically heterogeneous in the age of onset, the extent of organ involvement, and the rate of progression.
1.
Lacana E, Yao LP, Pariser AR, Rosenberg AS. 2012. The role of immune tolerance induction in restoration of the efficacy of ERT in Pompe disease., Am J Med Genet C Semin Med Genet. 2012 160C:30-39
Forward-Looking Statements
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 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-K for the year ended December 31, 2011. 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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Contact:
Investors/Media:Sara Pellegrinospellegrino@amicustherapeutics.com(609) 662-5044
