Next-gen Pompe therapy Nexviazyme reverses heart damage in baby boy
Case report findings may support early introduction of treatment in such cases
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A baby boy with infantile-onset Pompe disease and a severely enlarged heart was treated early with Nexviazyme (avalglucosidase alfa), a next-generation enzyme replacement therapy from Sanofi, leading to rapid and sustained improvement of heart function, according to a case report from Japan.
“These findings may support the early introduction of avalglucosidase alfa as a first-line therapy to reverse cardiac remodeling [structural alterations] and improve clinical outcomes in [infantile-onset Pompe disease],” researchers wrote in “Rapid Regression of Myocardial Hypertrophy with First-Line Avalglucosidase Alfa in Infantile-Onset Pompe Disease: A Case Report,” which was published in Pediatric Cardiology.
Enzyme replacement therapy is main Pompe disease treatment
Pompe disease is caused by the lack of a working version of an enzyme called acid alpha-glucosidase (GAA). This enzyme normally helps break down glycogen, a stored form of sugar, inside cells. When it is missing or does not work, glycogen builds up to toxic levels inside cells, especially muscle cells, and damages them.
In infantile-onset Pompe disease, symptoms usually appear within the first few months of life because GAA activity is almost absent. Babies may feed poorly due to muscle weakness, grow slowly, and have difficulty breathing. Heart problems are common and usually become apparent early. Without treatment, most babies develop heart failure in the first year of life.
The main treatment for Pompe disease is enzyme replacement therapy, which provides an artificial version of the missing enzyme through regular infusions into the bloodstream. In Japan, both Myozyme (alglucosidase alfa, marketed in the U.S. as Lumizyme) and Nexviazyme are approved for infantile-onset and late-onset Pompe disease, but Nexviazyme is expected to deliver the enzyme more effectively to muscle cells.
Boy’s heart showed muscle thickening soon after birth
This report describes the case of a baby boy with Pompe disease who was treated with Nexviazyme from early infancy. He was born to Chinese parents at 38 weeks of pregnancy with a normal weight, but soon after birth, a heart ultrasound showed thickening of the heart muscle, called left ventricular hypertrophy. At that time, he had normal muscle tone and no obvious muscle weakness.
Blood tests showed high creatine kinase, which can indicate muscle damage. Doctors initially suspected hypertrophic cardiomyopathy, a disease where the heart muscle becomes abnormally thick. Testing for a range of diseases did not reveal a clear cause, and testing for Pompe disease was not done because the baby had no muscle weakness.
At about 2 months of age, the baby developed poor feeding, and left ventricular hypertrophy was notably worse. He was readmitted to the hospital at 3 months with breathing difficulty and an enlarged liver. Heart measurements showed severe enlargement, and blood tests revealed very high levels of NT-proBNP, a marker of heart failure.
[Nexvizyme] may represent an effective first-line therapeutic option for [infantile-onset Pompe disease.
Because of the rapid worsening, Pompe disease was suspected. Testing showed very low GAA activity in the blood. Genetic testing confirmed two disease-causing mutations in the GAA gene, which encodes the enzyme. Based on these findings, the diagnosis of infantile-onset Pompe disease was confirmed.
Treatment with Nexviazyme was started at a dose of 40 mg per kilogram of body weight every two weeks. The baby also received medication to reduce fluid buildup in the lungs. Within one week of starting enzyme replacement therapy, heart size measurements began to improve, and symptoms of heart failure appeared to ease.
After eight weeks of treatment, the heart muscle thickness had decreased to about one-third of the baseline value. After sixteen weeks, heart measurements returned to the normal range. Blood markers of heart strain and muscle damage also gradually normalized. During the 3-year follow-up, the child’s heart size remained normal, and no breathing problems developed.
Growth and development were appropriate for age, and no treatment-related side effects were observed.
Nexvizyme “may represent an effective first-line therapeutic option for [infantile-onset Pompe disease],” the researchers wrote. In this case, its early use rapidly reversed heart problems, even when skeletal muscles, which control movement, have not been affected, they added.
