Eliglustat (Cerdelga) Approved in Europe for Gaucher Disease

Megan Brooks


January 22, 2015

The European Commission (EC) has approved eliglustat (Cerdelga, Genzyme) capsules for treatment of adults with type 1 Gaucher disease, a rare inherited disorder affecting fewer than 10,000 people worldwide.

Gaucher disease is caused by a deficiency of the enzyme glucocerebrosidase, which leads to a buildup of fatty materials in the spleen, liver, and bone marrow, leading to enlargement of the liver and spleen, anemia, low blood platelet counts, and bone problems.

Intravenous enzyme replacement has been standard treatment for Gaucher disease. Oral eliglustat is a glucosylceramide analog that inhibits the metabolic process that forms the fatty materials in patients with the enzyme deficiency.

In the European Union, eliglustat is indicated for long-term treatment of adults with type 1 Gaucher disease who are CYP2D6 poor metabolizers, intermediate metabolizers, or extensive metabolizers.

It is contraindicated in patients who are CYP2D6 intermediate metabolizers or extensive metabolizers taking a strong or moderate CYP2D6 inhibitor concomitantly with a strong or moderate CYP3A inhibitor, and in patients who are CYP2D6 poor metabolizers taking a strong CYP3A inhibitor.

The EC approved eliglustat based on studies involving about 400 patients with type 1 Gaucher disease treated in 29 countries, including two pivotal phase 3 studies, Genzyme notes in a news release.

In one phase 3 trial of treatment-naïve patients with Gaucher disease type 1, those receiving oral eliglustat had a greater reduction in spleen volume, and improvement in liver volume, blood platelet count, and hemoglobin level compared with those receiving placebo.

The second phase 3 trial assessed disease stability in patients previously treated with imiglucerase, an enzyme replacement therapy. Eliglustat proved noninferior to imiglucerase in terms of improvement in spleen volume, hemoglobin levels, platelet counts, and liver volume.

In a phase 2 clinical study in treatment-naïve patients, eliglustat showed a positive effect on bone parameters including bone marrow burden and bone mineral density, which was sustained over at least four years, the company notes.

The most common side effects with eliglustat (>2% of patients) are headache, nausea, diarrhea, abdominal pain, flatulence, arthralgia, and fatigue. The most frequently reported serious adverse reaction in clinical studies was syncope (0.76%). "All events were associated with predisposing risk factors and appeared to be vasovagal in nature. None of these events led to discontinuation from the study," the company says. They expect eliglustat to be available in Europe this year.

Eliglustat was approved by the US Food and Drug Administration in August 2014, and is under review by other regulatory authorities around the world.


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