Alnylam Presents Positive Complete Results from ENVISION Phase 3 Study of Givosiran, an Investigational RNAi Therapeutic for the Treatment of Acute Hepatic Porphyria - Seite 2

“Currently, there are no approved therapies aimed at preventing the painful, often incapacitating attacks and chronic symptoms associated with AHP,” said Manisha Balwani, M.D., M.S, Associate Professor of the Department of Genetics and Genomic Sciences and Department of Medicine at the Icahn School of Medicine at Mount Sinai and principal investigator of the ENVISION study. “The results from ENVISION are promising and demonstrate a strong treatment effect for givosiran, with reduction of attacks and improvement in patient-reported measures of overall health status and quality of life. Thus, givosiran represents a novel and targeted treatment approach that has the potential to make a significant impact on the lives of patients who are struggling with the disabling symptoms of this disease.”

Efficacy Results
Givosiran met the primary efficacy endpoint with a 74 percent mean reduction relative to placebo in the annualized rate of composite porphyria attacks, defined as those requiring hospitalization, urgent healthcare visit, or hemin administration, in patients with acute intermittent porphyria (AIP) over six months (p equal to 6.04x10^-9). There was a corresponding 90 percent median reduction in composite annualized attack rate (AAR), with a median AAR of 1.0 in givosiran patients compared with a median AAR of 10.7 in placebo patients. Fifty percent of givosiran-treated patients were attack-free during the six-month treatment period as compared to 16.3 percent of placebo-treated patients. The reductions in attack rates were observed across all components of the primary endpoint. The treatment benefit for givosiran compared to placebo was maintained across all pre-specified patient subgroups, including age, race, geography, historical attack rates, prior hemin prophylaxis status, disease severity, and other baseline characteristics.

Givosiran also demonstrated statistically significant differences in five of nine hierarchically tested secondary endpoints relative to placebo. These included mean reductions of:

• 91 percent in urinary aminolevulinic acid (ALA) in patients with AIP at three months (p equal to 8.74x10^-14).
• 83 percent in urinary ALA in patients with AIP at six months (p equal to 6.24x10^-7).
• 73 percent in urinary levels of porphobilinogen (PBG) in patients with AIP at six months (p equal to 8.80x10^-7).
• 77 percent in the number of annualized days on hemin in patients with AIP (p equal to 2.35x10^-5).
• 73 percent in composite AAR for patients with any AHP (p equal to 1.35x10^-8).

The remaining four secondary endpoints did not meet the prespecified criteria for statistical significance in hierarchical testing.