Long-term Cerezyme use improves health, growth for kids with Gaucher
Real-world gains also seen for children with more severe GD type 3
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Long-term treatment with Cerezyme (imiglucerase), or its discontinued predecessor Ceredase (alglucerase), led to rapid and progressive improvements in blood counts, growth, and bone health, as well as reductions in liver and spleen size, in children with Gaucher disease (GD) — including among youngsters with a more severe disease type.
That’s according to a real-world study that analyzed data from more than 1,000 children with Gaucher treated with these enzyme replacement therapies (ERTs), both from Sanofi. The analysis used data from 900 children with Gaucher disease type 1 (GD1), the rare disorder’s most common type, and more than 200 with Gaucher disease type 3 (GD3), defined by neurological symptoms that first appear in childhood.
“This is the largest, most comprehensive global evaluation of long-term [Cerezyme or Ceredase] therapy in pediatric GD1 and GD3,” the researchers wrote, noting that despite the more complex disease burden in type 3 Gaucher, treated children showed benefits similar to those seen in type 1 patients, including “meaningful growth improvements.”
“These findings emphasize the importance of early diagnosis and sustained treatment to optimize long-term outcomes,” the scientists noted.
The study, “The global impact of imiglucerase therapy in children with Gaucher disease types 1 and 3: a real-world analysis from the International Collaborative Gaucher Group Gaucher Registry,” was published in the Orphanet Journal of Rare Diseases. Five of the study’s 10 authors work for Sanofi.
Symptoms of Gaucher commonly include anemia, marked by low red blood cells, and thrombocytopenia, or low platelet counts that affect blood clotting. Patients may also have an enlarged spleen and liver, bone problems, and experience delayed growth. While Gaucher disease type 1 does not affect the brain, type 3 causes slowly progressing neurological symptoms that affect life expectancy.
ERTs such as Cerezyme are a mainstay of treatment for Gaucher. Administered through regular intravenous, or into-the-vein, infusions, these therapies provide the body with a lab-made version of the enzyme that is missing in Gaucher, helping ease disease symptoms.
Cerezyme now also approved in US for Gaucher type 3
In the U.S., Cerezyme was recently approved as a treatment for nonneurological symptoms in children and adults with Gaucher type 3, expanding its use beyond type 1.
The extension of Cerezyme’s approval for type 3 Gaucher was in part based on data from the International Collaborative Gaucher Group (ICGG) Gaucher Registry (NCT00358943), a Sanofi-sponsored database launched in 1991 that collects information from thousands of Gaucher patients worldwide.
As of January 2023, the registry had enrolled 961 children with Gaucher type 1 and 236 with type 3 disease who started either Cerezyme or its predecessor Ceredase before age 18 as their initial therapy. Ceredase is an older version of the drug that delivered a placenta-derived enzyme and was therapeutically equivalent to Cerezyme; it was discontinued with the introduction of safer, lab-made ERT options.
Most of the children in the study were from North America, Europe, and regions including the Middle East, Eurasia, and Africa.
Children with type 3 were generally younger at diagnosis (median 1.6 vs. 5.3) and at the start of treatment (1.9 vs. 7.8) than those with type 1, reflecting the more severe and rapidly progressing nature of this form of the disease. Overall, blood counts, liver and spleen size, and growth measures reflected a high disease burden and growth delays, which were more pronounced in children with type 3 than in those with type 1 disease.
“Height and weight [data recorded in the registry] reflect failure to thrive in the GD3 [patient group] and some children with GD1,” the researchers noted.
Gains seen across key disease measures, and in children’s growth
Following treatment, children in both groups showed rapid and sustained improvements across key disease measures.
Hemoglobin levels, a marker of anemia, and platelet counts increased significantly during the first year of treatment in both groups of children, the data showed. From year 1 to year 23, hemoglobin levels continued to rise at a slower pace in both groups. Platelet counts remained stable in boys with both disease types and continued to improve slightly in girls.
Liver and spleen size decreased significantly early in treatment. During the first year and a half, liver volume declined by about 20% per year in children with type 1 and about 24% per year in those with type 3. Spleen volume decreased by approximately 40% per year in both groups, the data showed. From 1.5 to 13 years, organ size continued to decrease, although at a slower rate, the researchers noted.
Our findings provide unequivocal evidence that [Cerezyme or Ceredase are] highly effective in reversing severe [blood and organ disease] burden and promoting sustained improvements in growth and bone health, even in the most profoundly affected children with GD.
Children also showed improvements in growth. Height and weight increased significantly during the first three years of treatment, and generally continued to increase or stabilize over as long as 17 years of follow-up.
The researchers also noted that estimated mean height and weight were within the normal range by age 18, indicating catch-up growth during treatment.
Bone mineral density, a measure of bone strength, also improved with treatment. From about four years after starting therapy through year 19, bone density increased gradually in children with both disease types, the data showed. By age 18, estimated values approached the normal range in both groups.
Such findings were consistent even after researchers accounted for differences in the age at which treatment was started.
“Leveraging the largest international [group] of children with GD1 and GD3, our findings provide unequivocal evidence that [Cerezyme or Ceredase are] highly effective in reversing severe [blood and organ disease] burden and promoting sustained improvements in growth and bone health, even in the most profoundly affected children with GD,” the researchers concluded, noting that the “therapy led to rapid and marked improvements.”
“Importantly, [blood and internal organ], skeletal, and most growth parameters — key indicators of disease severity in GD — were maintained within or moved into widely accepted therapeutic goal ranges during more than a decade of treatment,” the team wrote.
