Tips and Tricks from the Pompe Community

April 15, 2017 is the Fourth Annual International Pompe Day. The International Pompe Association (IPA), with the support of the global Pompe community, launched International Pompe Day in 2014. The goal of International Pompe Day is to raise global awareness of Pompe disease, a rare neuromuscular condition that affects approximately 1 in 40,000 people around the world.

When International Pompe Day was launched, the Pompe Community selected “Together We Are Strong” as its motto. We believe that as a united community of patients, family members, friends, scientists, doctors, and industry partners we have accomplished, and can continue to accomplish, great things. Together we have seen a treatment for Pompe become a reality for most people around the world, and working together we see new and better treatments on the horizon in the near future.

This year, as a global community we turn our attention and advocacy power to the importance of “Living Healthy with Pompe Disease”. Pompe disease is just one part of the Pompe individual’s life. To have a healthy lifestyle, those without Pompe have to eat healthy, sleep well, and stay active. The same is true for those with Pompe. And it can be a struggle to find the right balance, and the right approach to achieve a healthy lifestyle for all of us.

For this year’s International Pompe Day, the IPA would like to raise awareness of the benefits of “Living Healthy with Pompe” for everyone diagnosed with Pompe disesae. We understand the challenges that people can face because of the effects of Pompe, and want to provide support and encouragement to everyone. When trying to incorporate new habits and lifestyle goals it can be overwhelming at the beginning. You don’t know where to start, and it is easy to get discouraged. The ways to “Live Healthy” are as diverse as the Pompe Community, and it is our goal on International Pompe Day to support our Community as they strive to define what “Living Healthy with Pompe” means for each of them.

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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• Press release (external link)
• Press release (PDF 140 kB)

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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• Press release (external link)
• Press release (PDF, 42 kB)

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