Higher doses of Lumizyme may improve infantile Pompe survival

Best outcomes seen among patients getting 2 to 4 times approved dose

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Higher doses of Lumizyme (alglucosidase alfa) than what’s approved may improve survival outcomes for children with classic infantile onset Pompe disease (IOPD), according to a new study.

An analysis of data from the Pompe Registry collected over nearly two decades showed that IOPD patients given Lumizyme at higher doses were also less likely to need invasive ventilation to support their breathing.

“We provide results from 332 IOPD patients from the Pompe Registry to describe changes in [Lumizyme] dosing over time and to demonstrate a robust association between higher [Lumizyme] doses (up to four times the label dose) and improved survival and invasive ventilation-free survival,” the researchers wrote in “Higher dose alglucosidase alfa is associated with improved overall survival in infantile-onset Pompe disease (IOPD): data from the Pompe Registry,” which was published in the Orphanet Journal of Rare Diseases.

“Our study provides the largest data analysis, to the best of our knowledge, of the association between higher [Lumizyme] doses and treatment outcomes in IOPD,” they said.

Pompe disease is caused by mutations in the gene that provides instructions for making the acid alpha-glucosidase (GAA) enzyme, which results in the complex sugar glycogen building up to toxic levels in tissues. Classic IOPD is the most severe form, with symptoms that include cardiomyopathy (heart damage) in the first year of life.

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Lumizyme dose has gotten higher over time

Lumizyme is an approved enzyme replacement therapy that delivers a working version of GAA into the body. The approved dosage is 20 mg/kg of body weight, given by infusion into the bloodstream every two weeks.

Here, researchers analyzed data from 332 children with classic IOPD who were started on Lumizyme in their first year of life. Nearly two-thirds (64.2%) were positive for cross-reactive immunologic material (CRIM), a marker of an immune response to the medication that can affect its efficacy.

In most patients (81.3%), Lumizyme was given at more or less the approved dosing schedule. But nearly one in five (18%) patients started at higher doses, most commonly 20 mg/kg every week instead of every other week.

While the doses varied over time, about half (51.8%) the patients were on a higher than approved dose at some point. Generally, higher doses were more common in the years after the therapy was approved.

“The frequency of administration of high dose [Lumizyme] has increased over time, with more patients beginning treatment on higher doses and more patients receiving higher doses over the course of their treatment,” the researchers wrote, noting the finding “illustrates the changing trends in clinical practice and clinical characteristics of patients with Pompe disease over time since the market availability of” Lumizyme.

Over the follow-up, about one in four (26.5%) children died, at a median age of less than 2 years. Most of those who died were taking the approved dosage at the time of death and statistical analyses indicated that higher doses were associated with better survival outcomes.

Specifically, analyses indicated that, for every one-unit increase in the average relative dose of Lumizyme, the risk of death was decreased by 60%. The best survival outcomes were seen among patients receiving somewhere between double and quadruple the approved dose. In these patients, the risk of death was about 90% lower than in those given the approved dosed.

Similar results were found with the risk of needing a ventilator and the researchers noted the association between higher Lumizyme doses and better survival “was consistent across sensitivity analyses and patient subgroups and was noted irrespective of age at first treatment.”

The Pompe Registry is funded by Sanofi, Lumizyme’s developer.