Synageva BioPharma (GEVA) announced Monday after the close that the phase 3 ARISE trial of lead drug candidate sebelipase alfa successfully met its primary endpoint, and the company will file a New Drug Application early next year. The stock was flat in after-hours trading, illustrating how widely these results were expected by the investing community.
The ARISE (Acid Lipase Replacement Investigating Safety and Efficacy) trial tested sebelipase alfa in 66 children and adults with lysosomal acid lipase (LAL) deficiency, a rare disorder in which the body does not produce enough lysosomal acid lipase enzyme, which is central to breaking down fatty material in the body. The deficiency leads to dangerous fat build-up in major organs, including the liver and spleen.
Patients enrolled in the trial were randomized on a one-to-one basis to sebelipase alfa (1 mg/kg) or placebo for 20 weeks. Sebelipase alfa demonstrated a statistically significant improvement in alanine aminotransferase (ALT) normalization (p=0.027) and dyslipidemia, present in a majority of patients at baseline: reductions in LDL cholesterol (p<0.001), non-HDL cholesterol (p<0.001) and triglycerides (p=0.038), as well as a statistically significant increase in good cholesterol (HDL) (p<0.001) when compared to placebo.
Synageva also reported statistically significant improvements in AST normalization (p<0.001) and in liver fat fraction (p<0.001). In 26 patients available for paired liver biopsies at baseline and at 20 weeks, 63% of patients treated with sebelipase alfa (10/16) had improvement in hepatic steatosis, vs. 40% on placebo (not stat. sig). Following the 20-week blinded portion of the trial, all 66 patients rolled over to active therapy, according to the company.
