Treatment with Lumizyme (alglucosidase alfa) at double the approved dose may help prevent the rapid decline of respiratory and cardiovascular functions in infants with Pompe disease, a case report suggests.
Since the U.S. Food and Drug Administration approved it in 2006, Lumizyme has change the course of Pompe disease for many patients. This enzyme replacement therapy (ERT) was developed by Sanofi Genzyme to overcome the lack of GAA enzyme that characterizes the disease, preventing the accumulation of glycogen in the body.
Lumizyme’s FDA-approved dose is 20 mg per kilogram of body weight, administered every two weeks as an infusion into the vein. Despite the effectiveness of this treatment regimen, about 50% of treated patients with infantile onset Pompe disease still require ventilator support by 3 years of age. Some reports have suggested that a higher dose of Lumizyme may be more effective in preventing respiratory, cardiovascular, and motor decline.
In the case report, “Pompe disease treatment with twice a week high dose alglucoside alfa in a patient with severe dilated cardiomyopathy,” a team at Medical College of Wisconsin presented the case of an infant with Pompe disease who they treated with double dose of Lumizyme — 40 mg per kilogram of body weight. The report was published in the journal Molecular Genetics and Metabolism Reports.
The infant was 3 months old when he was taken to his primary care physician for the third time since birth due to persistent congestion, cough, and runny nose. The symptoms were initially thought to be due to an upper respiratory infection, but he also had a history of poor feeding, failure to thrive, and low muscle tone.
After a chest radiography, the physician noticed he had an enlarged heart, and referred him to the Children’s Hospital of Wisconsin, where he was admitted. Based on his clinical presentation, the team at the hospital strongly suspected he had infantile onset Pompe disease.
Further analysis confirmed he had low GAA enzyme activity, which was consistent with the suspected Pompe diagnosis.
In the meantime, his cardiac condition got worse, and he started treatment with Primacor (milrinone) for heart failure. On the following day, he started treatment with 40 mg/kg of Lumizyme twice a week. Because it was unclear what his immune status was, he was also treated with 0.4 mg/kg of Trexall (methotrexate) to manage autoimmunity, characterized by antibodies against the body’s own tissues.
On the 12th day of treatment, he was also started on a beta blocker, Coreg (carvedilol), in addition to the other medications to manage his cardiac condition. His health started to progressively improve without the need for respiratory support or supplemental oxygen.
He was treated with 40 mg/kg twice a week for a total of 21 infusions until he was 6 months old when he was transitioned to a regimen of 40 mg/kg once a week. At 8 months old, an intravenous catheter and gastrostomy tube were placed to allow treatment administration and proper feeding.
“We speculate that this increased dose may have decreased the length of stay the patient required in the cardiac intensive care unit and his total hospital length of stay,” the researchers wrote.
Supported by the significant improvements experienced by this infant severely affected by Pompe disease, the team suggests that a higher dose of Lumizyme “is a reasonable consideration to aid in recovery.”