Four-year follow-up data from patients enrolled in the phase 2 clinical trial for its investigational oral therapy for Gaucher disease type, 1 known as Eliglustat tartrate, have shown sustained improvements in all endpoints, including markers of bone disease.

Eliglustat tartrate, a novel glucosylceramide analog given orally, is being developed to provide a convenient treatment alternative for adult patients with Gaucher disease type 1.
Cerezyme ( Imiglucerase for injection ), the standard of care for patients with Gaucher disease type 1, is administered through intravenous infusions.

The 52-week results from this study were previously reported; Eliglustat tartrate met primary composite endpoint: a clinically meaningful response in at least two of three endpoints ( improvements in spleen size, hemoglobin and platelet levels ) in individual patients. Patients have continued to receive Eliglustat tartrate in the extension portion of the study for over four years. The data from patients on Eliglustat tartrate after four years have indicated continued or stabilized improvements across all endpoints: spleen and liver volumes decreased from baseline by a mean of 63% and 28%, respectively; hemoglobin and platelet levels had increased from baseline by a mean of 2.3 g/dL and 95%, respectively; all patients had met at least three of the four hematologic and visceral therapeutic goals established for enzyme replacement therapy. These data also have indicated continued improvement in bone mineral density by DXA, with a mean T-score increase of 0.8 from baseline in the lumbar spine.

In the phase 2 study, the most common adverse events reported in greater than two patients through four years of treatment included viral infections ( 6 patients ), urinary tract and upper respiratory tract infections ( 4 patients each ), and nasopharyngitis, sinusitis, arthralgia, pain in extremity, headache, increased blood pressure, abnormal nerve conduction study, abdominal pain, and diarrhea ( 3 patients each ). Ten drug-related adverse events, including one serious event, were reported in 8 patients. All related events were mild in severity.

Genzyme has also fully enrolled all three phase 3 trials for the oral therapy. Combined, these trials represent the largest clinical program ever focused on Gaucher disease, with participating sites in over 30 countries. In total, more than 350 patients are enrolled in the phase 3 studies.
The first phase 3 trial, ENCORE, is a randomized, open-label study for adult patients with Gaucher disease type 1, designed to compare Eliglustat tartrate to Imiglucerase. Adult patients who previously received enzyme replacement therapy for at least three years and have reached their therapeutic goals are enrolled in this trial. The second trial, ENGAGE, is a randomized, double-blind, placebo-controlled study for patients with Gaucher disease type 1 who were untreated or had not been on treatment for at least nine months prior to study entry. A third trial, known as EDGE, compares once-daily dosing of Eliglustat tartrate with twice-daily dosing.

Gaucher disease is an inherited condition affecting fewer than 10,000 people worldwide. People with Gaucher disease do not have enough of an enzyme, beta-glucosidase ( glucocerebrosidase ) that breaks down a certain type of fat molecule. As a result, lipid engorged cells ( called Gaucher cells ) amass in different parts of the body, primarily the spleen, liver and bone marrow. Accumulation of Gaucher cells may cause spleen and liver enlargement, anemia, excessive bleeding and bruising, bone disease and a number of other signs and symptoms. The most common form of Gaucher disease, type 1, generally does not affect the brain.

Source: Genzyme, 2012

XagenaMedicine2012