Concord, MA-- March 3, 2017-- Valerion Therapeutics announced today that it has developed a fusion protein, VAL-1221, which combines its proprietary antibody delivery technology with recombinant human acid alpha-glucosidase (rhGAA) to improve the delivery of rhGAA into affected tissues of patients with Pompe disease (Glycogen Storage Disease, Type II; GSDII). Pompe disease is caused by a deficiency of the lysosomal enzyme, GAA, that leads to accumulation of glycogen in multiple tissues, with cardiac and skeletal muscles being the most severely affected. Glycogen, a complex sugar, is known to accumulate in both the lysosomes and cytoplasm of late-onset Pompe disease patients. However, the currently approved enzyme-replacement therapy is limited to the lysosome for therapeutic activity.

In a study recently published by Sun et al, Duke University, Division of Medical Genetics (J Mol Med, 2 Feb, 2017), Valerion’s proprietary antibody-mediated enzyme replacement therapy [VAL-1221 (humanized 3E10Fab-GAA)] demonstrated efficacy in both cultured Pompe patient fibroblasts and in Pompe (GAA-deficient) mice. Importantly, not only did VAL-1221 reduce lysosomal glycogen accumulation as effectively as rhGAA (current enzyme replacement therapy or ERT) but it was also demonstrated to penetrate living cells independent of the mannose-6-phopsphate receptor (M6PR), the mechanism of cell entry associated with current ERT which directs enzyme to the lysosome. These results suggest that VAL-1221 has potential benefit over current ERT by clearing both lysosomal and cytoplasmic glycogen.

Valerion is initiating a clinical trial in both the US (Duke University Medical Center) and the UK (The National Hospital for Neurology and Neurosurgery, London) next month to evaluate this novel therapy in patients with late-onset Pompe disease.

“We believe our findings are a game-changer in the treatment of Pompe disease,” said Deborah Ramsdell, Valerion’s Chief Executive Officer. “We are excited about the potential to help patients who are looking for alternatives to the current approved therapy.” This randomized, parallel active control, single and repeat dose, dose-escalation study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy of VAL-1221 in ambulatory and ventilator-free patients with late-onset Pompe Disease. Top line results are expected later this year. 100 Main Street, Suite 110, Concord, MA 01742

“The approach is different from other ERT approaches as this has the ability to act on glycogen in the cytoplasm. This remains a challenge in the field of Pompe disease,” said Dr. Priya Kishnani, Principal Investigator at Duke University Medical Center. “Glycogen that is leached out (either due to shearing effect or rupture of lysosomes) into cytoplasm needs to be cleared. The collaboration with Valerion is an important one as it allows us to look at whether VAL-1221 has this additional benefit.” ...

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CRANBURY, N.J., March 01, 2017 (GLOBE NEWSWIRE) -- Amicus Therapeutics (Nasdaq:FOLD)... provided program updates. John F. Crowley, Chairman and Chief Executive Officer of Amicus Therapeutics, Inc. states that "establishing our novel Pompe treatment paradigm ATB200/AT2221 as a highly differentiated therapy" is one of five key strategic priorities...

Program Update: ATB200/AT2221 for Pompe Disease

ATB200/AT2221 is a novel treatment paradigm that consists of ATB200, a unique recombinant human acid alpha-glucosidase (rhGAA) enzyme with optimized carbohydrate structures, particularly mannose-6 phosphate (M6P), to enhance uptake, co-administered with AT2221, a pharmacological chaperone. Positive preliminary data were reported in the fourth quarter of 2016  and during the 13th Annual WORLDSymposium™ in San Diego, CA in February 2017 from a global clinical study (ATB200-02) to evaluate safety, tolerability, PK, and pharmacodynamics (PD) of ATB200/AT2221. The study is enrolling 3 cohorts of patients, including ambulatory ERT-switch patients (Cohort 1), non-ambulatory ERT-switch patients (Cohort 2), and ERT-naïve patients (Cohort 3).

Key Preliminary Data Highlights from ATB200-02 Study in Initial ERT-Switch and ERT-Naïve Patients:

• No infusion-associated reactions following 150+ infusions in initial patients treated for a maximum of 36 weeks (n=13)
• Available PK and PD (muscle and glycogen biomarkers) data through week 18 in eight initial ERT-switch patients and two ERT-naïve showed:
  • The desired PK profile
  • Improvements in key muscle damage biomarkers (creatine kinase (CK) enzyme, alanine aminotransferase (ALT), and aspartate aminotransferase (AST)) in a majority of ERT-switch patients and both ERT-naïve patients
  • Reductions in a biomarker of glycogen substrate urine hexose tetrasaccharide (Hex4) in all patients
• Target enrollment achieved across all patient cohorts 

Anticipated Upcoming Pompe Disease Program Milestones:

• ATB200-02 study data in additional naïve and non-ambulatory patients, as well as extension-phase data on all patient cohorts, in the second and third quarter of 2017
• Meetings with US and EU regulators

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Disclaimer: The IPA does not endorse any of the products, medications, treatments or information reported herein. Articles on the IPA web pages are intended for informational purposes, only. We strongly advise that you discuss all medications, treatments, and/or products with your physician.

CRANBURY, N.J. and SAN DIEGO, Feb. 15, 2017 (GLOBE NEWSWIRE) -- Amicus Therapeutics (Nasdaq:FOLD)... today presented additional positive preliminary data from a global Phase 1/2 study (ATB200-02) to investigate ATB200/AT2221 in a poster at the 13th Annual WORLDSymposium™ in San Diego, CA. ATB200/AT2221 is a novel treatment paradigm that consists of ATB200, a unique recombinant human acid alpha-glucosidase (rhGAA) enzyme with optimized carbohydrate structures, particularly mannose-6 phosphate (M6P), to enhance uptake, co-administered with AT2221, a pharmacological chaperone.

"We are very pleased to share these additional positive preliminary clinical results here at the WORLDSymposium as we continue with the cascade of data from this important study in Pompe Disease patients," said John F. Crowley, Chairman and Chief Executive Officer of Amicus Therapeutics, Inc. "In addition to excellent continued safety, tolerability and PK profile, we now see evidence that this novel Amicus treatment paradigm is further reducing important biomarkers of disease in both ERT-switch patients as well as in the first ERT-treatment naïve patients.  In particular, demonstrating with these data that we can further reduce these biomarkers in a switch population is very encouraging. To our knowledge, there are no published data for other Pompe ERTs where these types of reductions in biomarkers have been shown. Moreover, the fact that these biomarkers have demonstrated a sustained reduction in a majority of patients over the first 18 weeks suggests that the effects of our approach may indeed be persistent and durable. We look forward to data in more patients and over longer periods of time in the months ahead, including important measures of muscle function in these patients. We could not be more pleased with the preliminary data to date."...

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Disclaimer: The IPA does not endorse any of the products, medications, treatments or information reported herein. Articles on the IPA web pages are intended for informational purposes, only. We strongly advise that you discuss all medications, treatments, and/or products with your physician.