ERT and Chaperone Combination for Pompe Disease Showing Promise

At the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) Annual Meeting in Phoenix, Arizona, data from Amicus’ enzyme replacement therapy (ERT) and chaperone drug combination for treating patients with late-onset Pompe disease was presented.

Preliminary results look promising for this early in-development therapy.

Pompe disease is a rare lysosomal disease that may present in childhood (early-onset) or later (late-onset). In both cases, the disease is due to a deficiency in the enzyme alpha-glucosidase (GAA). Patients with late-onset Pompe disease will often grow up being able to walk but begin to lose muscle strength as they age.

The data presented by Swati Sathe and colleagues examined preliminary safety and pharmacokinetic / pharmacodynamic (PK/PD) in patients taking 2 drugs in development by Amicus Pharmaceuticals— ATB200, a GAA ERT, and AT2221, a chaperone medication designed to enhance ATB200’s efficacy.

The current treatment option for Pompe disease is the lumizyme, a GAA ERT by Genzyme. While effective, the newer ERT, ATB200, has significantly higher levels of mannose-6-phosphate (M6P) that should increase lysosomal targeting, the cellular vesical in which GAA is needed.

Since enzymes are prone to degradation in the blood, the addition of a pharmacological chaperone AT2221 should also, theoretically, improve the efficacy of ATB200. AT2221 is designed to bind to ATB200 and help stabilize the enzyme until it reaches its target.

At the AANEM meeting, preliminary safety (n=13) and pharmacokinetic/pharmacodynamic (PK/PD) (n=10) data was presented in adults with Pompe disease receiving ATB200 alone compared to ATB200 in combination with AT2221.

Single 4-hour IV infusions of ATB200 at 5, 10, and 20 mg/kg demonstrated slightly greater than dose-proportional exposures.

Oral administration with AT2221 prior to ATB200 infusion increased total GAA protein terminal-phase partial area under the curve (AUC) by approximately 25% and plasma half-life by approximately 45% relative to ATB200 20 mg/kg alone.

Plasma AT2221 showed dose-proportional kinetics with peak concentrations 2 hours into infusion.

Muscle injury biomarkers (aspartate aminotransferase, alanine aminotransferase, and creatine kinase) were shown to improve or stabilize in the patients while urinary Hex4 levels decreased.

The drugs were well-tolerated. All adverse events (AEs) were considered mild, and none led to treatment discontinuation.

The authors concluded that the combination of ATB200/AT2221 is safe and well tolerated and the increased exposure and half-life of ATB200 when co-administered with AT2221 confirms the intended mechanism of action of chaperone drug.


Sathe S, Bratkovic D, Byrne B, et al. First-in-human preliminary PK and safety data on a novel recombinant acid a-glucosidase, ATB200, co-administered with pharmacological chaperone (PC) AT2221 in patients with late-onset Pompe disease. Presented at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) Annual Meeting; Phoenix, Arizona; September 13-16, 2017. Abstract #100.

Read more

Leave A Comment

Your email address will not be published. Required fields are marked *