Myozyme at Higher Dose More Effective for Classic Infantile Pompe, Study Says

Classic infantile Pompe disease is the most severe form of the disease. In these infants, GAA levels are usually lower than 1%, reflected in an inability to achieve important motor developmental milestones, such as walking. Without prompt treatment, infants with classic infantile Pompe do not live past their first year.

Enzyme replacement therapy (ERT) is currently considered the gold standard treatment for Pompe disease. The approach works by providing the enzyme patients are missing.

Myozyme, sold under the brand name Lumizyme in the U.S., is an ERT marketed by Sanofi Genzyme that has been approved to treat patients of all ages and types of Pompe disease. It was approved in the EU in 2006.

In general, Myozyme is recommended to be given by an intravenous infusion (directly into the bloodstream) at a dose of 20 mg/kg every other week. However, in infants who are cross-reactive immunologic material (CRIM)-negative and tend to produce neutralizing antibodies against the therapy, this dosing schedule is less effective.

CRIM measures the amount of GAA that patients are able to produce. In general, those who are CRIM-positive respond better to ERT than patients who are CRIM-negative.

Researchers at Erasmus MC University Medical Center in the Netherlands presented the latest findings of a study aimed to determine if a more frequent and higher Myozyme dosing schedule would be more beneficial to infants with classic infantile Pompe, particularly those who were CRIM-negative.

Their analyses were based on data (collected through Dec. 31, 2016) from 18 children, including five who were CRIM-negative. Six had been treated at the recommended 20 mg/kg dosing schedule, and 12 received the medication at a weekly dose of 40 mg/kg.

All classic infantile Pompe patients newly diagnosed at this center have been treated at the higher dosing schedule since 2009, the researchers wrote. Those who started earlier on the lesser dosing schedule were moved to the 40 mg/kg schedule between 2009 and 2014 “due to clinical deterioration.”

The study’s main goal was to compare the effects of these two dosing schedules on a series of long-term outcomes, including the time children lived without requiring respiratory support and their ability to achieve key motor milestones.

Levels of neutralizing antibodies produced against the therapy were also measured in both groups.

Infants age 2 months or older who enrolled in the study after 2012 were treated with Myozyme at 40 mg/kg weekly and also received immunomodulation treatment with rituximab, methotrexate, and intravenous immunoglobulins (IVIG). The aim was to see if this immunomodulation provided extra benefits.

Study findings showed that  nearly all (92%) children in the higher and more frequent dosing schedule lived without requiring respiratory support over the course of the study, as did half of those on the recommended dosing schedule.

Likewise, nearly all (92%) infants on the highest and more frequent doses of Myozyme learned to walk, while the corresponding percentage in those receiving standard treatment was lower (67%).

The two CRIM-negative infants treated with the recommended dosage of Myozyme died during the study. All three CRIM-negative children who given Myozyme weekly at 40 mg/kg were alive at the study’s end.