The pivotal phase III clinical trial was a multi-center, world-wide, randomized, double-blind, parallel group, dose-ranging study, to assess the safety and efficacy of taliglucerase alfa in 31 treatment-naive patients suffering from Gaucher disease.
In the trial, patients were selected randomly for one of two dosing arms (60U/kg or 30U/kg) and received intravenous infusions of taliglucerase alfa once every two weeks, for a nine month period. The primary endpoint of the study was a 20% mean reduction from baseline in spleen volume after nine months, as measured by MRI. Major secondary endpoints were an increase in hemoglobin, decrease in liver volume and increase in platelet count. The trial enrolled patients at 11 centers throughout Europe, Israel, North America, South America and South Africa.
Taliglucerase alfa reduced mean spleen volume after nine months compared with baseline in both treatment groups. The 60U/kg group demonstrated a statistically significant mean reduction in spleen volume of 38.0% (p<0.0001) and the 30U/kg group demonstrated a significant mean reduction in spleen volume of 26.9% (p<0.0001). In addition, the primary endpoint was achieved in both treatment groups after six months of therapy.
Statistically significant improvements were also observed for the secondary endpoints after nine months when compared to baseline for the 60U/kg dose. Patients demonstrated a mean increase in hemoglobin of 2.2g/dl or 22.2% (p<0.0001), a mean decrease in liver volume of 11.1% (p<0.0001) and a mean elevation in platelet count of 41,494ml or 72.1% (p=0.0031). For patients in the 30U/kg dose, statistically significant improvements after nine months, compared to baselines were observed for hemoglobin level (increased 1.6g/dl or 14.8%; p=0.0010) and liver size (decreased 10.48%; p=0.0041); a nominal elevation in platelet count was also seen (11,427ml or 13.7%; p=0.0460).
Over 30 patients in the trial had Chitotriosidase measurements, a biomarker for clinical symptoms of Gaucher disease. In these patients, Chitotriosidase decreased from baseline in both the 30U/kg and 60U/kg groups by 47.3% and 58.4%, respectively.
The safety analysis for both treatment groups showed that taliglucerase alfa was well tolerated and no serious or severe adverse events were reported.
David Aviezer, president and CEO of Protalix, said: “The Phase III results reported today not only support the use of taliglucerase alfa for the treatment of Gaucher disease, but also support the company’s plant cell based platform technology. Patients who successfully completed this pivotal study have continued to receive taliglucerase alfa as part of our ongoing extension trial, some for over two and a half years.”