Cerdelga (eliglustat) is a substrate reduction therapy (SRT) for the long-term treatment of adult patients with Gaucher disease type 1.

An SRT like Cerdelga reduces the amount of the fat molecule glucosylceramide in patients, giving the GCase enzyme less of it to break down. The drug, developed by Sanofi Genzyme, was the first oral treatment approved by the U.S. Food and Drug Administration (FDA) for the treatment of Gaucher disease type 1. It was approved in 2014.

Gaucher disease is an inherited condition that affects the production of the enzyme responsible for breaking down glucosylceramide. As a result, these fat molecules accumulate inside cells that store lipids, which makes them larger. This can happen in several parts of the body, but primarily takes place in the spleen, liver, and bone marrow.

How Cerdelga works

Unlike enzyme replacement therapy (ERT) for Gaucher disease, which increases the degradation of fat molecules, Cerdelga reduces the body’s production of glucosylceramide by partially inhibiting the enzyme which creates it: glucosylceramide synthase.

This approach reduces the rate of accumulation of the fat molecules in Gaucher cells and allows for the working enzymes to keep degrading glucosylceramide at a slower pace.

Cerdelga in clinical trials

The FDA approval of Cerdelga was based on data obtained from two Phase 3 clinical trials to test the effectiveness of the drug in the treatment of Gaucher disease. One of the trials enrolled patients who were new to therapy (the ENGAGE trial), while the trial switched patients from enzyme replacement therapies (the ENCORE trial).

In the ENGAGE trial (NCT00891202), after nine months of treatment, improvements were seen in spleen size, platelet levels, hemoglobin levels, and liver volume. Gaucher patients continued to receive treatment in the extension period, and the majority of patients have been on treatment for more than 18 months. The randomized, double-blind, placebo-controlled study enrolled 40 patients.

The ENCORE trial (NCT00943111) showed that the effectiveness of Cerdelga treatment was not inferior compared to enzyme replacement therapy with imiglucerase and was able to improve spleen and liver volume, hemoglobin levels, and platelet counts. Patients continued to receive treatment in the extension period, and the majority of participants have been on treatment for more than two years. This randomized, open-label study enrolled 160 patients.

Genzyme also designed a Phase 3, randomized, double-blind study to compare the effectiveness, safety, and pharmacokinetics of a once-daily and twice-daily dose of Cerdelga for the treatment of Gaucher disease type 1 patients.

The 52-week EDGE trial (NCT01074944) enrolled 170 patients who received either 100 mg or 200 mg of Cerdelga, accordingly to disease progression, either once or twice daily. The difference in dosage did not seem to generate different effects or alter the safety of the treatment.

The most common side effects of treatment with Cerdelga were fatigue, headache, nausea, diarrhea, and pain in the back, arms and legs, and upper abdomen.

Patients from the now-completed trials are being recruited to join a new Phase 3, open-label trial called EXOSKEL (NCT02536755) that aims to evaluate the long-term skeletal response of Cerdelga in 40 Gaucher patients.

Other information

Cerdelga can interfere with other medicines. Therefore, using Cerdelga with other medications or herbal supplements may cause an increased risk of side effects, including heart complications.

Cerdelga should not be used in patients taking strong or moderate liver enzyme inhibitors (CYP2D6 or CYP3A inhibitors) due to the risk of significantly increasing the concentration of Cerdelga in the blood, which may result in prolonging cardiac intervals that could result in cardiac arrhythmias.

It is not known whether Cerdelga is safe and effective in children.

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