Protalix Presents Updated Data on Taliglucerase Alfa

A multinational phase III trial of taliglucerase alfa (Uplyso) found that it improved several clinical indicators in patients with type 1 Gaucher disease. Unlike imiglucerase alfa, which is mammalian based, or velaglucerase alfa, which is human based, taliglucerase alfa is a plant-based enzyme replacement therapy. Hanna Rosenbaum, MD, director of the Hematology Day Care Unit, RAMBAM Medical Center, Haifa, Israel, led the study and said, “I believe the data from the phase III trial demonstrates that taliglucerase alfa is well tolerated and clinically effective in treating Gaucher disease. Data were presented at the Lysosomal Disease Network World Symposium 2010 in Miami, Florida.

In the double-blind trial, 31 previously untreated patients were randomly assigned to receive 60 U/kg or 30 U/kg of taliglucerase alfa intravenously every 2 weeks for 9 months. “The primary endpoint was reduction in spleen volume,” Rosenbaum said. Using MRI, investigators hoped to see a 20% mean reduction in spleen volume after 9 months of treatment. Secondary endpoints included a decrease in liver volume and increases in hemoglobin levels and platelet counts.

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Both treatment arms showed a significant reduction in mean spleen volume after the 9-month treatment period. The 60 U/kg group saw a decline of 38.0% from baseline and the 30 U/kg group had a mean decrease of 26.9% in spleen volume ( <.0001 for both arms). “Both dose groups reached the endpoint already after 6 months’ treatment with highly statistical significance,” said Rosenbaum.

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Patients in both groups also experienced statistically significant improvement in the secondary endpoints of liver volume and hemoglobin levels. Patients taking the 60 U/kg dose had a mean decrease in liver volume of 11.1% ( <.0001) and those in the 30 U/kg dosing arm saw liver volume decline by 10.48% ( = .0041). Improvement in hemoglobin levels was greater in the high-dose group, at 2.2 g/dL (22%), which was statistically significant ( <.0001). In the low-dose group, hemoglobin change was 1.6 g/dL (14.8%, = .0010). “A subanalysis was performed in a group of anemic patients,” Rosenbaum said. “It shows an increase of 3.7 g/dL of hemoglobin following treatment with 30 U/kg and 3.1 g/dL on 60 U/kg.” At 60 U/kg, Rosenbaum said there was an “impressive increase of 72% in platelet count,” ( = .0031). The platelet count increase was nominal in the 30 U/kg group, at 13.7% ( = .0460).

Chitotriosidase measurements were taken for 30 patients at baseline. Chitotriosidase is a biomarker for clinical symptoms of Gaucher disease. Median decrease from baseline was 47.3% in the low-dose group and 58.4% in the high-dose group.

“No serious adverse events were reported. All adverse events were mild or moderate in intensity and the majority of these events resolved spontaneously,” said Rosenbaum. Two patients exhibited antibodies to taliglucerase alfa, but none developed neutralizing antibodies. Investigators also reported 2 hypersensitivity reactions but no anti-taliglucerase antibodies. Other adverse events, many not believed to be treatment related, included headache, dizziness, muscle spasm, chest discomfort, nausea, skin irritation, and arthralgia.

Rosenbaum concluded, “Taliglucerase alfa decreased the spleen liver volume, increased hemoglobin and platelet counts, and decreased biomarkers [and produced] a marked improvement in chitotriosidase, which was seen and observed in all patients in the study.” Several of the patients have been treated with the novel drug for more than 2-1/2 years as part of an extension trial, and a worldwide switchover study is ongoing. Protalix, which makes taliglucerase alfa, recently signed an agreement with Pfizer that allows Pfizer to sell the drug everywhere except Israel, for which Protalix will retain marketing rights. Protalix filed a New Drug Application with the FDA, which earlier this month requested additional information on the company’s manufacturing facilities. Efficacy data for imiglucerase for injection, taliglucerase alfa, and velaglucerase alfa have been similar.