Global Open-label Extension: 24-month Data in Patients with hATTR Amyloidosis
David Adams1, Alejandra Gonzalez-Duarte2, Elizabeth Mauricio3, Thomas Brannagan4, Teresa Coelho5, Jonas Wixner6, Erhan Berber7, Marianne Sweetser7, Matthew White7, Jing Jing Wang7, Michael Polydefkis8
1APHP, 2Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, 3Mayo Clinic, 4Columbia University, 5Unidate Clinica de Paramoloidose Hospital, 6Umeå University, 7Alnylam Pharmaceuticals, 8Johns Hopkins University School of Medicine
Objective:
To describe interim 24-month efficacy and safety analyses of the ongoing Global Open-Label Extension (OLE) study.
Background:
Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive, life-threatening disease. The efficacy and safety of patisiran has been demonstrated in Phase 3 (APOLLO) and Phase 2 Open-Label Extension (OLE) studies in patients with hATTR amyloidosis with polyneuropathy.
Design/Methods:
International OLE study (NCT02510261) in eligible patients who completed parent studies, including APOLLO patients randomized to placebo (APOLLO/placebo, n=49) or patisiran (APOLLO/patisiran, n=137) and Phase 2 OLE patients (n=25). 
Results:
As of 10/07/2019, 178/211 patients had 24-month assessments. Safety profile remained consistent with previous studies. After 24 months of additional patisiran treatment in the OLE, 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 vs. parent study baselines. Norfolk QOL-DN continued to show durable improvement in APOLLO/patisiran patients (-2.4 [2.4]) following additional 24-months treatment. In the Global OLE, APOLLO/placebo patients experienced halting of disease progression and quality of life (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 progression while on placebo in APOLLO.
Conclusions:
Patients with long-term exposure to patisiran continue to demonstrate durability of 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.