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Oral Eliglustat (Cerdelga) Scores in Treatment of Gaucher’s Disease

Positive phase III data support long-term use

Positive results have been reported from two phase III studies of eliglustat (Cerdelga, Genzyme/Sanofi), a first-line oral therapy approved by the FDA for the treatment of certain adults with type-1 Gaucher’s disease.

The findings were presented February 12 at the 11th Annual Lysosomal Disease Network WORLD Symposium in Orlando, Florida. Both studies demonstrated continued stability and/or improvements across established endpoints and therapeutic treatment goals.

The ENGAGE trial was a randomized, double-blind, placebo-controlled study in patients with type-1 Gaucher’s disease. In the primary analysis period, improvements were seen across the following endpoints after 9 months of treatment with oral eliglustat: spleen size, platelet count, hemoglobin concentration, and liver volume. In a 9-month extension phase, patients who switched from placebo to eliglustat showed improvements similar to that of the eliglustat-treated patients during the primary analysis. The eliglustat-treated patients continued to show improvements during the 9-month extension period. There were no treatment-related discontinuations.

The ENCORE trial was a randomized, controlled, open-label, non-inferiority study comparing eliglustat with imiglucerase (Cerezyme, Genzyme) in patients with type-1 Gaucher’s disease stabilized on enzyme replacement therapy. The study, which met the primary analysis criteria for non-inferiority to imiglucerase, had a composite endpoint of each of the following parameters: spleen volume, hemoglobin concentration, platelet counts, and liver volume at 12 months. During a 12-month extension period, the patients who crossed over to eliglustat treatment from imiglucerase remained stable. Patients treated with eliglustat for 24 months also maintained the stability of clinical parameters during the extension period.

The most common adverse reactions observed during the primary analysis periods of the ENGAGE and ENCORE trials included fatigue, headache, nausea, diarrhea, back pain, pain in the extremities, and upper abdominal pain. In both extension studies, most adverse reactions were mild and transient, and were consistent with those in the primary analysis periods.

Most patients in both phase III studies continue to receive eliglustat in longer-term extension periods. The majority of patients are now in their fourth or fifth year of treatment.

Gaucher’s disease is an inherited condition affecting fewer than 10,000 people worldwide. People with the disorder do not have enough of the enzyme beta-glucosidase (glucocerebrosidase), which leads to the accumulation of its substrate, glucosylceramide. As a result, lipid-engorged cells (Gaucher cells) accumulate in different parts of the body, primarily in the spleen, liver, and bone marrow. The accumulation of Gaucher cells may cause splenomegaly, hepatomegaly, anemia, excessive bleeding and bruising, bone disease, and several other signs and symptoms. The most common form of Gaucher’s disease, type 1, generally does not affect the brain.

Eliglustat was designed to partially inhibit the enzyme glucosylceramide synthase, which results in reduced production of glucosylceramide.

Cerdelga (eliglustat) capsules are indicated for the long-term treatment of adults with type-1 Gaucher’s disease who are cytochrome P450 2D6 (CYP2D6) poor metabolizers, intermediate metabolizers, or extensive metabolizers, as detected by an FDA-cleared test. Patients who are CYP2D6 ultra-rapid metabolizers may not achieve adequate concentrations of eliglustat to achieve a therapeutic effect. A specific dose cannot be recommended for patients whose CYP2D6 genotype cannot be determined (indeterminate metabolizers).

Source: Genzyme; February 12, 2015.

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