Date: 2015-02-17
Type of information: Publication of results in a medical journal
phase: 3
Announcement: publication of results in The Journal of the American Medical Association (JAMA)
Company: Genzyme (USA - MA), a Sanofi company (France)
Product: Cerdelga® (eliglustat tartrate)
Action
mechanism: enzyme inhibitor/ceramid analog. Eliglustat is an analog of D-threo-1-phenyl-2-decanoylamino-3-morpholino-propanol. This is a specific ceramide analogue inhibitor of glucosylceramide synthase (IC50 = 10 ng/mL) with broad tissue distribution. It works by blocking the enzyme beta-glucosylceramide synthase, slowing the production of glucocerebroside, the substance that builds-up in patients\' lysosomes. Patients with Gaucher disease type 1 retain some residual glucocerebrosidase enzyme activity and Cerdelga aims to slow the formation of the lipid to help balance the cell\'s ability to clear it. On August 19, 2014, the FDA approved Cerdelga® (eliglustat) capsules. On January 19, 2015, the European Commission (EC) also granted marketing authorization for Cerdelga® .
Disease: Gaucher disease
Therapeutic area: Rare diseases - Genetic diseases
Country:
Trial
details: The ENGAGE study is a Phase 3 randomized, double-blinded, placebo-controlled, multinational registration trial of 40 eligible treatment-naïve patients with Gaucher disease type 1 who had splenomegaly in addition to thrombocytopenia and/or anemia at study entry. Patients were stratified by baseline spleen volume and randomized 1:1 to receive Cerdelga® (50 or 100 mg twice daily) or placebo for nine months, following assessment for improvements in disease manifestations.
Latest
news: * On February 17, 2015, Sanofi and its subsidiary Genzyme, announced the publication of results from the ENGAGE registration study evaluating Cerdelga® (eliglustat) in treatment-naïve patients with Gaucher disease type 1 in the February 17, 2015 issue of The Journal of the American Medical Association. The primary efficacy endpoint of the study demonstrated a statistically significant reduction from baseline in spleen size by a mean of 28 percent compared in Cerdelga® patients with a mean increase of two percent in placebo patients, for an absolute difference of 30 percent (P less than 0.0001). Secondary endpoints were also statistically significant: - Hemoglobin levels increased from baseline by an absolute difference of 1.2 g/dL compared with placebo (P=0.006) - Liver volume decreased from baseline by an absolute difference of 6.6 percent compared with placebo (P=0.0072) - Platelet levels increased from baseline by an absolute difference of 41 percent compared with placebo (P less than 0.0001) There were no serious adverse events associated with either treatment group. All adverse reactions reported in the primary analysis period of the ENGAGE study were mild or moderate and included arthralgia, headache, migraine, flatulence, nausea, and oropharyngeal pain (all occurring in greater than 10% of Cerdelga® treated patients and more frequently than placebo). One patient withdrew from the trial for a reason not related to treatment. At the end of the nine months, patients who were on placebo were transitioned to Cerdelga®. (Effect of Oral Eliglustat on Splenomegaly in Patients With Gaucher Disease Type 1 - The ENGAGE Randomized Clinical Trial. Pramod K et al. JAMA. 2015;313(7):695-706. doi:10.1001/jama.2015.459)
