Rare Disease Report

New Cerdelga Data Continues to Impress

FEBRUARY 16, 2017
James Radke

Cerdelga (eliglustat) is the most recent orphan drug to be approved for treating Gaucher disease type 1 but unlike the other treatments, this one take be taken orally.  So is it as good as the more traditional enzyme replacement therapies in the long run?
At the WORLDSymposium meeting in San Diego this year, the answer seems to be yes.
Mistry et al presented long term data – 4.5 years – showing the drug to continue to be safe and effective.

Phase 3 Study

Cerdelga (eliglustat) is an oral substrate reduction therapy, is a first-line treatment for adults with Gaucher disease type 1 (GD1) with poor, intermediate, or extensive CYP2D6-metabolizer phenotypes.  Its approval was partially based on a phase 3 study – The ENGAGE Trial — that was published in JAMA in 2015.

The ENGAGE trial was a double-blind, randomized, placebo-controlled trial in which  40 adult patients (> 16 yrs) with type 1 Gaucher disease received either Cerdelga or placebo for 39 weeks. The primary endpoint was spleen volume and compared to placebo, treatment with Cerdelga resulted in a greater reduction in spleen volume from baseline to the end of the 39 week study.  Cerdelga also showed greater improvement in liver volume, blood platelet count, and red blood cell (hemoglobin) level, compared to placebo.

Open Label Extension

At WORLDSymposium, Mistry et al reported on 39 patients who entered the open-label extension phase of the ENGAGE study in which they received eligustat for 2.5 to over 4.5 years.

Among patients with 4.5 years of data, mean spleen and liver volumes decreased by 66% and 23%, respectively, and mean hemoglobin level and platelet count increased by 1.4 g/dL and 87%, respectively.

Among the 33 patients with ≥ 2.5 years of data, 91% met all 3 of the 4 therapeutics goals for Gaucher treatment (increased hemoglobin levels; eliminate blood transfusion dependency; reduce fatigue, dyspnea, angina; maintain improved Hb levels).

Mean spine T-score increased by a mean of 21%, and median levels of thebiomarkers chitotriosidase, GL-1, and MIP-1β decreased by 82%, 79%,and 71%, respectively.

The drug was generally well-tolerated; 99% of all 559 adverse events and all 7 serious adverse events were mild or moderate. No patients discontinued due to adverse events.

About Gaucher Disease

Gaucher disease is an inherited lysosomal storage disorder in which a deficiency of the enzyme glucocerebrosidase leads to the accumulation of the lipid glucocerebroside within the lysosomes of the monocyte-macrophage system. The most common form of this rare disease is Gaucher type 1 and its current treatment options are:

  • Cerezyme (imiglucerase for injection):  Cerezyme is the gold standard for ERT and has been treating people with Gaucher disease since 1994. It is administered by intravenous infusion every 2 weeks.
  • Vpriv (velaglucerase alfa for injection): Vpriv was approved in March 2010 of Vpriv and has also been shown to relieve or reverse many of the signs and symptoms of Type 1 Gaucher disease.  It is also an enzyme replacement therapy and administered by intravenous infusion every 2 weeks.
  • Elelyso (taliglucerase alfa): Elelyso was approved by the FDA in June 2012 for the treatment of Gaucher disease type 1.  It has not been given approval in Europe (based on the argument that Elelyso and Vpriv are too similar).  The key biochemical difference of Elelyso compared to the above enzyme replacement therapies is that it is derived from plant (carrot). It is administered by intravenous infusion every 2 weeks.
  • Zavesca (miglustat). In addition to the above ERTs, there is also the option of using substrate reduction therapy for patients who cannot take enzyme replacement therapy. Zavesca was approved by the FDA in July 2003. It is an oral medication (3 times per day).
  • Cerdelga (eliglustat): Cerdlelga is the first non ERT that can be used instead of ERT (unlike Zavesca that is only approved for patients who cannot take ERT).



Mistry PK, Lukina E, Turkia HB, et al. Effects of oral eliglustat on splenomegaly in patients with Gaucher disease type 1: The ENGAGE randomized clinical trial. JAMA 2015;313:695-706.

Mistry PK, Lukina E, Turkia HB, et al. Long-term results of ENGAGE: a phase 3, randomized, double‑blind, placebo-controlled, multi‑center study investigating the efficacy and safety of eliglustat in adults with type 1 Gaucher disease. Presented at WORLDSymposium 2017; February 13-17, 2017; San Diego, CA. http://dx.doi.org/10.1016/j.ymgme.2016.11.243


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