Jing Jing Wang (United States of America)
Alnylam Pharmaceuticals Clinical ResearchAuthor Of 1 Presentation
GLOBAL OPEN-LABEL EXTENSION: 24-MONTH DATA OF PATISIRAN IN PATIENTS WITH HATTR AMYLOIDOSIS
- Marco Luigetti (Italy)
Abstract
Background and Aims:
Hereditary transthyretin-mediated (hATTR) amyloidosis, is a progressive, life-threatening disease. Patisiran’s efficacy/safety have been demonstrated in Phase 2 and 3 studies in patients with hATTR amyloidosis with polyneuropathy. Interim 24-month efficacy/safety analyses of the ongoing Global OLE study are described.
Methods:
Multicenter, international, OLE, safety/efficacy study (NCT02510261) in patients who completed parent studies, including patients in the Phase 3 APOLLO randomized to placebo (n=49) or patisiran (n=137) over 18 months and patients in the Phase 2 OLE (n=25) receiving patisiran over 24 months.
Results:
178/211 patients enrolled in the Global OLE had at least 24 months of exposure as of October 7, 2019. Safety profile remained consistent with previous studies. After 24 months of additional patisiran treatment, durable improvement was seen for mNIS+7 (mean change [SEM]) in APOLLO/patisiran (-4.9 [2.1]) and Phase 2 OLE (-5.9 [2.1]) groups compared to their parent study baselines. Norfolk QOL-DN continued to show durable improvement in APOLLO/patisiran patients (-2.4 [2.4]). APOLLO/placebo patients experienced halting of disease progression and QOL improvement compared to Global OLE baseline after 24 months of patisiran (mNIS+7: +0.1 [3.3], Norfolk QOL-DN: -4.1 [3.3]), although they had progressed relative to APOLLO baseline (mNIS+7: +26.3 [5.0], Norfolk QOL-DN: +15.8 [4.5]) given the progression while on placebo.
Conclusions:
In the Global OLE, patisiran continue to demonstrate long-term durable efficacy. Despite marked progression on placebo during APOLLO, previously untreated patients continue to exhibit halting of disease progression and QOL improvement following 24 months of patisiran. Patisiran continues to demonstrate a positive benefit:risk profile.