This study investigated whether patients with Gaucher's disease stable on a alternate-week infusion of enzyme replacement therapy would remain so after switching to oral eliglustat, a selective inhibitor of glucosylceramide synthase. The composite primary efficacy endpoint was percentage of patients whose haematological variables and organ volumes remained stable for 12 months (i.e. haemoglobin decrease not > 15 g/L, platelet count decrease not > 25%, spleen volume increase not >25%, and liver volume increase not > 20%, in multiples of normal from baseline). The non-inferiority margin was 25% for eliglustat relative to imiglucerase, assessed in all patients who completed 12 months of treatment. In the per-protocol population, 84 (85%) of 99 patients who completed eliglustat treatment and 44 (94%) of 47 patients who completed imiglucerase treatment met the composite primary endpoint (between-group difference −8·8%; 95% CI −17.6 to 4.2); the lower bound of 95% CI of −17.6% was within prespecified threshold for non-inferiority. The researchers note their study is the first to show that adults with Gaucher's disease type 1 who are stable on intravenous infusions of enzyme therapy can safely maintain stable haematological and organ measures after switching to oral eliglustat treatment.
According to a commentary, the availability of a convenient oral treatment creates a new opportunity to explore a role for early treatment in preventing the late and unusual manifestations of Gaucher's disease. Long-term postregistration studies in sizeable cohorts are needed to confirm the findings in a mouse model of type 1 Gaucher's disease that administration of eliglustat prevents development of monoclonal gammopathy, lymphoma, and myeloma.
In January 2015, eliglustat was approved in the EU for the treatment of Gaucher’s disease.