Treatment-naïve Gaucher disease patients achieve therapeutic goals and normalization with velaglucerase alfa by 4 years in phase 3 trials

Abstract

Gaucher disease is an inherited metabolic disease characterized by β-glucocerebrosidase deficiency and commonly treated with enzyme replacement therapy (ERT). The efficacy of ERT with velaglucerase alfa was assessed based on the achievement of published therapeutic goals and the normalization of disease parameters in 39 treatment-naïve patients with type 1 Gaucher disease, 6 to 62years of age, enrolled in phase 3 clinical trials. After 4years of ERT, therapeutic goals for thrombocytopenia and splenomegaly had been achieved in 100% of patients; goals for anemia and hepatomegaly had been achieved in 95% and 94% of patients, respectively. Consistent with the goal for bone mineral density, lumbar spine bone density improved in 87% of patients ≥18years of age. At year 4, compared with clinical ranges for healthy individuals, 86% of patients with a low baseline hemoglobin concentration had normalized, 60% with a low baseline platelet count had normalized, 67% with baseline splenomegaly had normalized, 58% with hepatomegaly had normalized, and lumbar spine bone density had normalized in 53% of adults. The decade-old therapeutic goals do not reflect the potential for normalization of clinical parameters in ERT-treated patients. Goals consistent with normalization or near-normalization should be considered. ClinicalTrials.gov identifiers: NCT00430625, NCT00553631, NCT00635427.

Demographics and patient characteristics of 1209 patients with Gaucher disease: Descriptive analysis from the Gaucher Outcome Survey (GOS)

“…It will be informative to monitor the response of the GOS population to long‐term ERT use, particularly for patients with clinical signs of disease at GOS entry who receive velaglucerase alfa. Previous studies have shown that velaglucerase alfa normalized hematological, visceral, and skeletal disease parameters in treatment‐naïve patients with type 1 GD in the clinical trial setting, and it would be interesting to see if similar results are obtained in a “real‐world” setting.…”

Finding and Treating Gaucher Disease Type 1 – The Role of the Haematologist

“…8 The vast majority of patients with GD type 1 present with haematological complications, including spontaneous bruising/bleeding due to thrombocytopenia and/or GD-associated coagulopathy, abdominal discomfort/swelling due to splenomegaly and/or chronic fatigue due to anaemia. 2,4,[8][9][10] Other symptoms, including hepatomegaly and abnormal liver function, increased susceptibility to infection due to suboptimal neutrophil function and neutropenia, pulmonary disease, bone pain and (in children) growth retardation and/or delayed puberty may also be present. GD type 1 (Online Mendelian Inheritance in Man ® [OMIM ® ] number 230800) -the most common and mildest form of the disorder -is usually distinguished from types 2 and 3 (OMIM numbers 230900 and 231000, respectively) by the absence of neurological symptoms.…”

“…Prompt treatment of GD type 1 with ERT can prevent or reverse many of the clinical features associated with this condition, thereby improving quality of life. 1,3,9,20,[22][23][24][25][26][27][28][29] For example, a study of 884 patients with GD type 1 found that, when initiated during childhood, 8 years' continuous treatment with ERT was associated with the normalisation/nearnormalisation of Hb levels, platelet count, liver and spleen volumes, and mean bone mineral density z-score, with significant reductions in the incidence of bone crises. 24 Conversely, a study in 17 patients with GD with delayed diagnosis (up to 10 years) found that approximately 25% developed irreversible complications including avascular bone necrosis, severe bleeding, chronic bone pain, life-threatening sepsis, pathologic fractures, growth failure and liver pathology.…”

“…31 Perhaps surprisingly, the Gaucher Outcomes Study (GOS) found that, of the 1,209 participants with diagnosed GD, at least 174 (14.4%) patients remained untreated. 9 Whereas some of these patients may have had mild or absent symptoms that (physicians believed) did not warrant expensive pharmacological treatments, others may not have had access to required medications. Nonetheless, results suggest that management delays in patients with GD might be confounded by a lack of awareness regarding the benefits of prompt treatment.…”

Long-Term Safety and Effectiveness of Velaglucerase Alfa in Gaucher Disease: 6-Year Interim Analysis of A Post-Marketing Surveillance in Japan

“…Long-term ERT with velaglucerase alfa has demonstrated an ability to stabilize the symptoms of GD and slow disease progression, improving platelet counts, hemoglobin levels, plasma biomarkers and liver and spleen volume in patients with Type 1 disease [19,20]. ERTs have limited e cacy in treating the neurological symptoms of GD because the infused enzyme molecules are too large to cross the bloodbrain barrier.…”