Improvements in Skeletal Manifestations in Gaucher Disease Type 1 Patients After 3 Years of Treatment with Oral Eliglustat During a Phase 2 Trial

• Published in: Blood 2011-11, Vol.118 (21), p.3216-3216
• Main Authors: Peterschmitt, M. Judith, Kamath, Ravi S, Lukina, Elena, Watman, Nora, Dragosky, Marta, Iastrebner, Marcelo, Pastores, Gregory M, Arreguin, Elsa Avila, Phillips, Mici, Rosenbaum, Hanna, Sysoeva, Elena, Aguzzi, Rasha, Ross, Leorah H, Puga, Ana Cristina, Rosenthal, Daniel I
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V118.21.3216.3216

Abstract 3216▪▪This icon denotes a clinically relevant abstract In Gaucher disease type 1 (GD1), deficient lysosomal acid β-glucosidase leads to accumulation of undegraded glucosylceramide in lysosomes of tissue macrophages known as Gaucher cells. Skeletal complications are a major cause of morbidity and include bone marrow infiltration by Gaucher cells, osteopenia/osteoporosis, lytic lesions, fractures, avascular necrosis, and bone pain. Eliglustat, a novel, oral inhibitor of glucosylceramide synthase, is under investigation for the treatment of GD1. To report skeletal changes after 3 years of eliglustat therapy. This ongoing, open-label, uncontrolled, multicenter, Phase 2 clinical trial enrolled 26 adults with GD1 not on treatment for the previous 12 months, who had splenomegaly with thrombocytopenia and/or anemia. Study entry criteria also required that patients had no new pathologic bone involvement or bone crises within the preceding 12 months and not have used bisphosphonates during the previous 3 months. Changes from baseline were reported for centrally reviewed skeletal x-rays, dual-energy x-ray absorptiometry (DXA) and MRI assessments. Of 26 enrolled patients, 19 completed 3 years of treatment. In 15 patients with evaluable DXA results at baseline and at 1, 2, and 3 years, mean lumbar spine BMD increased by 0.6±0.69 Z-score (baseline, −1.28), with greatest increases seen in osteoporotic patients. Mean femur BMD (T- and Z-score) remained normal through 3 years. Femur dark marrow on MRI, which reflects bone marrow infiltration by Gaucher cells, was reduced in 56% (10/18) or stable in 44% (8/18) of patients with findings at baseline. No bone crises or reductions in mobility occurred. On baseline radiographs, no patients had fractures, 42% (8/19 patients) had femoral lytic lesions, and 37% (7/19 patients) had bone infarcts. After 3 years, the lumbar spine and femurs showed no new lytic lesions, bone infarcts, fractures, or areas of osteonecrosis and no worsening of pre-existing lytic lesions or bone infarcts. One patient had worsening of asymptomatic osteonecrosis after 1 year noted retrospectively at baseline. Eliglustat was well-tolerated. Most adverse events (AEs) were mild and unrelated to treatment; the most common were viral infections (6 patients); urinary and upper respiratory tract infections (4 patients each); and headache, increased blood pressure, abdominal pain, diarrhea (3 patients each). Eight drug-related AEs, all mild, occurred in 6 p