Long-term safety and efficacy of patisiran in patients with hATTR amyloidosis: Global OLE study

Introduction: hATTR amyloidosis is a progressive, life-threatening disease. Patisiran’s efficacy/safety were demonstrated in Phase 2 and Phase 3 (APOLLO) studies in hATTR amyloidosis with polyneuropathy. Safety/efficacy from interim analysis of the Global Open-Label extension (OLE) study are presented.

Methods: Multicenter, international, OLE, safety and efficacy study (NCT02510261) in eligible patients who completed parent studies; APOLLO patients randomized to placebo (APOLLO/placebo, n=49) or patisiran (APOLLO/patisiran, n=137) and Phase 2 OLE (n=25).

Results: 211 patients enrolled; 189 had 12-month assessments by 9/24/2018. Safety remained consistent with previous studies After additional 12 months in the Global OLE, durable improvement was seen for mNIS+7 (mean change [­SEM]) in APOLLO/patisiran (-4.0 [1.9]) and Phase 2 OLE (-4.7 [3.5]) groups vs parent study baselines. Norfolk QOL-DN also showed durable improvement in APOLLO/patisiran patients (-3.9 [2.1]). APOLLO/placebo patients experienced improvement after 12 months of patisiran (mNIS+7: -1.4 [2.4], Norfolk QOL-DN: -4.5 [2.5]), although they progressed relative to APOLLO baseline (mNIS+7: +24.0 [4.2], Norfolk QOL-DN: +15.0 [3.4]) given progression while on placebo in APOLLO.

Conclusions: Long-term patisiran treatment continues to show a positive benefit:risk profile, including patients dosed for >4 years. Patients with longer-term exposure to patisiran demonstrated durability of effect. Despite marked progression on placebo during APOLLO, previously untreated patients exhibited halting of disease progression and QOL improvement following 12 months of patisiran. However, delay in treatment resulted in these patients accumulating greater disease burden vs patients treated earlier with patisiran