Genzyme Corporation (NASDAQ: GENZ) today announced three-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. Sustained or further improvements were observed across all endpoints, including bone disease, at the three-year timepoint. The results were presented for the first time this week at the Lysosomal Disease Network WORLD Symposium in Las Vegas, Nevada.
“These data suggest that eliglustat tartrate may have a meaningful clinical impact on bone disease in Gaucher disease type 1 patients.”
Genzyme previously reported that the eliglustat tartrate phase 2 trial had met its primary endpoint at one year, and that data demonstrated continued improvement through two years. The primary composite endpoint was a clinically meaningful response in at least two of three endpoints: improvements in spleen size, hemoglobin and platelet levels. The study has continued with 19 patients through three years. The extension phase of this trial is still ongoing.
Eliglustat tartrate continued to show robust clinical response through three years:
- Spleen volume decreased from baseline by a mean of 61 percent and liver volume decreased from baseline by 29 percent.
- Hemoglobin level increased from baseline by a mean of 2.6 grams per deciliter.
- Platelet count increased from baseline by a mean of 91 percent.
The study also analyzed the clinical response of patients in the phase 2 trial with respect to achieving therapeutic goals. Due to the heterogeneity of Gaucher disease, therapeutic goals were previously developed by experts involved in the treatment of Gaucher patients to assess their response to enzyme replacement therapy (ERT). Most patients dosed with eliglustat tartrate met established therapeutic goals for hemoglobin, platelets, spleen volume and liver volume, demonstrating progressive and clinically meaningful responses in multiple organ systems. At three years, 100 percent of patients met at least 3 of the 4 therapeutic goals developed for hematologic and organ volume parameters.
The three-year data also included analyses that suggest eliglustat tartrate positively impacts indicators of bone disease through three years of follow up. These indicators include bone mineral density in the lumbar spine, as measured by dual energy x-ray absorptiometry (DXA), and dark marrow signal in the femur, as visualized by magnetic resonance imaging (MRI). Dark marrow reflects the infiltration of lipid-laden Gaucher cells into bone marrow. Specifically:
- In the 18 patients at baseline with dark marrow in the femur visible by MRI, five improved by one year, seven by two years and 10 by three years, with the other eight patients remaining stable.
- In the 15 patients with results available at all time points, bone mineral density in the lumbar spine showed clinically and statistically significant improvements after one year of treatment (T score = +0.4) which further improved after 2 years (T score = +0.6) and were sustained after three years of treatment.
Ravi S. Kamath, M.D., Ph.D., Staff Radiologist at Massachusetts General Hospital and Instructor in Radiology at Harvard Medical School, who is the central radiology reviewer for the phase 2 study, said, "These data suggest that eliglustat tartrate may have a meaningful clinical impact on bone disease in Gaucher disease type 1 patients."
The most common adverse events (AEs) reported in greater than 2 patients through three years included viral infections (six patients), urinary tract infections and upper respiratory infections (4 patients each), headache, increased blood pressure, diarrhea and abdominal pain (three patients each). Eight drug-related AEs, including one serious event, were reported in six patients. Most AEs overall and all drug-related AEs were considered mild. The largest number of AEs was reported during the first 3 months of treatment.
"For thirty years, Genzyme has pioneered treatments for patients with lysosomal storage disorders, including the very first enzyme replacement therapy for Gaucher disease," said Genzyme's President, Personalized Genetic Health, John P. Butler. "Our momentum continues through the phase 3 trials - the largest ever conducted for Gaucher - as we build upon our foundation and commitment to Gaucher and look to extend the therapeutic options available to patients and physicians."
Eliglustat tartrate, a capsule taken orally, is being developed to provide a convenient treatment alternative for adult patients with Gaucher disease type 1, and to offer a broader range of treatment options for patients and physicians to achieve individual therapeutic goals. Genzyme is currently enrolling patients in three global, multi-center, phase 3 trials of eliglustat tartrate. This is the largest clinical program ever focused on Gaucher disease, with over 50 sites in more than 25 countries currently participating. Genzyme's Gaucher disease portfolio also offers Cerezyme® (imiglucerase for injection), the standard of care for patients with Gaucher disease type 1, which is administered through intravenous infusions.