A Phase 2 clinical trial of Genz-112638 for Gaucher disease type 1 met its primary endpoint.

Genzyme is developing Genz-112638, a capsule taken orally, to provide a convenient treatment alternative for adult patients with Gaucher disease type 1, and to provide a broader range of treatment options for patients and physicians to achieve individual therapeutic goals.
Currently, Cerezyme ( Imiglucerase for injection ) is administered through intravenous infusions.

The study had a composite primary efficacy endpoint: a clinically meaningful response in at least two of three endpoints ( improvements in spleen size, hemoglobin and platelet levels ) in individual patients after the 52-week study period.
Twenty-two of 26 study participants completed at least 52 weeks of treatment. After the study concluded, all 20 of the patients who were eligible chose to remain on treatment. More than half of the participants have completed more than two years of treatment.

The data for the 52-week analysis indicate that Genz-112638 demonstrated robust efficacy results in that 91 percent of those who completed 52 weeks achieved the primary endpoint:

At 12 months, spleen volumes had decreased from baseline by a mean of 39 percent and liver volumes had decreased from baseline by 17 percent.

At 12 months, hemoglobin levels had increased from baseline by a mean of 1.62 grams per deciliter of blood.

At 12 months, platelet counts increased from baseline by a mean of 40 percent with Genz-112638.

At 12 months, chitotriosidase levels decreased from baseline by a median of 51 percent, among the 20 patients treated with chitotriosidase. Chitotriosidase is commonly monitored by physicians as a biomarker of Gaucher disease burden and response to treatment.

The safety analysis demonstrated that Genz-112638 was well tolerated and has a promising safety profile. Ninety-one percent of adverse events were reported to be unrelated to drug treatment.
Drug-related adverse events occurred in a small number of patients early in treatment, were mild and transient in nature, and did not require any medical intervention.
Related adverse events in the Phase 2 study included infrequent abdominal discomfort and diarrhea, as well as transient palpitations and headache. Asymptomatic non-sustained ventricular tachycardia detected on study assessments have occurred when drug levels were below quantifiable limits. Subsequent reviews by three expert cardiologists reveal an unlikely relationship to Genz-112638.

Gaucher disease is an inherited condition affecting fewer than 10,000 people worldwide. People with Gaucher disease do not have enough of an enzyme, ß-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, does not affect the brain or nervous system.

Genz-112638, a novel glucosylceramide analog given orally, is designed to partially inhibit the enzyme glucosylceramide synthase, which results in reduced production of glucosylceramide. Glucosylceramide is the substance that builds up in the cells and tissues of people with Gaucher disease.

Source: Genzyme, 2009

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