Genzyme, a Sanofi company (EURONEXT: SAN and NYSE: SNY), announced today 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. Sustained or further improvements were observed across all endpoints, including markers of bone disease, at the four-year timepoint. The results will be presented for the first time this week at the Lysosomal Disease Network WORLD Symposium in San Diego, Calif.
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's Cerezyme® (imiglucerase for injection), the standard of care for patients with Gaucher disease type 1, is administered through intravenous infusions.
Genzyme previously reported that the 52-week phase 2 trial of eliglustat tartrate had met its 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 indicate continued or stabilized improvements across all endpoints:
- Spleen and liver volumes decreased from baseline by a mean of 63 percent and 28 percent respectively.
- Hemoglobin and platelet levels had increased from baseline by a mean of 2.3 g/dL and 95 percent respectively.
- All patients (100 percent) had met at least three of the four hematologic and visceral therapeutic goals established for enzyme replacement therapy.
- These data also indicate continued improvement in bone mineral density by DXA, with a mean T-score increase of 0.8 from baseline in the lumbar spine.
"Eliglustat tartrate represents a new hope for Gaucher disease type 1 patients," said Manisha Balwani, MD, MS, Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine. "The option of an oral therapy offers convenience, expanded access to treatment and, most important, an improvement in the quality of life for patients. Eliglustat tartrate marks a potential paradigm shift in Gaucher treatment."
"The four-year data from our phase 2 eliglustat tartrate study show very encouraging results, particularly the continued improvements observed in markers of bone disease," said Genzyme's Head of Rare Diseases, Rogerio Vivaldi, MD. "The efficacy of eliglustat tartrate, combined with its safety profile, demonstrate its potential to transform the treatment experience for the Gaucher community. We look forward to continuing our momentum in the phase 3 program."
In the phase 2 study, the most common adverse events reported in greater than two patients through four years of treatment included viral infections (six patients), urinary tract and upper respiratory tract infections (four patients each), and nasopharyngitis, sinusitis, arthralgia, pain in extremity, headache, increased blood pressure, abnormal nerve conduction study, abdominal pain, and diarrhea (three patients each). Ten drug-related adverse events, including one serious event, were reported in eight 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 Cerezyme. 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. Data from these pivotal registration studies are expected in the first half of 2013. A third trial, known as EDGE, compares once-daily dosing of eliglustat tartrate with twice-daily dosing.