Alnylam Presents New Clinical Results for Givosiran at the 2019 International Congress on Porphyrins and Porphyrias - Seite 2

ENVISION Results of Select Patient Reported Outcomes
A number of patient reported outcomes were collected as secondary and exploratory measures in the ENVISION study. Daily worst pain did not achieve statistical significance based on the prespecified ANCOVA analysis (p equals 0.0530), however, the data were found to not be normally distributed. A post-hoc analysis of daily worst pain was therefore performed using the non-parametric stratified Wilcoxon test. Based on the non-parametric test, patients on givosiran had a significant reduction in daily worst pain (nominal p equals 0.0455). In exploratory analyses, the reductions in pain were accompanied by fewer days of use of both opioid and non-opioid analgesics. Givosiran did not impact daily worst fatigue or daily worst nausea at six months, although these assessments will be repeated at twelve months to explore the effects of longer term dosing.

Change from baseline at six months of the Physical Component Summary (PCS) of the Short Form 12 (SF-12) health and quality of life questionnaire was a secondary endpoint that showed a trend favoring givosiran compared to placebo (nominal p equals 0.0216). There was consistent evidence of effect favoring givosiran compared to placebo (nominal p less than 0.05 for each) in the SF-12 domains of bodily pain, social functioning, and role physical (a domain that assesses limitations in routine activity due to physical impairment). The Patient Global Impression of Change (PGIC) at six months was an exploratory endpoint. The majority (59 percent) of givosiran treated patients reported their health status as “very much improved” or “much improved” since the beginning of the study compared to 18 percent of placebo patients reporting their status as “much improved”. Similarly, the Porphyria Patient Experience Questionnaire (PPEQ) at six months was assessed as an exploratory endpoint. On all eight items of the PPEQ, a greater proportion of patients on givosiran, relative to patients on placebo, reported improvements. In particular, a higher proportion (67 percent versus 11 percent) of givosiran-treated patients versus those on placebo reported “always” or “most of the time” in response to the question about the role of the study drug in helping them return to a more normal life over the prior four weeks.