Abstract Details

Title Global Open-label Extension: 24-month Data in Patients with hATTR Amyloidosis

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) S32 - Therapeutics of Genetic Neuromuscular Diseases (4:00 PM-4:08 PM)

Poster/Presentation
Number 001

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.

Objective To describe interim 24-month efficacy and safety analyses of the ongoing Global Open-Label Extension (OLE) study.

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.

Authors/Disclosures
Michael J. Polydefkis, MD, FAAN (Johns Hopkins University School of Medicine) PRESENTER	Dr. Polydefkis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alnylam Pharmaceuticals. Dr. Polydefkis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Akcea. Dr. Polydefkis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Vertex Pharmaceutical . Dr. Polydefkis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen-Idec. Dr. Polydefkis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pfizer.
David D. Adams (APHP)	David D. Adams has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for ALNYLAM. David D. Adams has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pfizer.
	No disclosure on file
Elizabeth A. Mauricio, MD, FAAN (Mayo Clinic)	Dr. Mauricio has nothing to disclose.
Thomas Brannagan III, MD, FAAN (Columbia University)	Dr. Brannagan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pfizer. Dr. Brannagan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alnylam. Dr. Brannagan has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Grifols. Dr. Brannagan has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for CSL. Dr. Brannagan has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alnylam. The institution of Dr. Brannagan has received research support from Alnylam. The institution of Dr. Brannagan has received research support from Acceleron. The institution of Dr. Brannagan has received research support from Ionis. The institution of Dr. Brannagan has received research support from Pharnext.
Teresa Coelho, MD (Unidate Clinica de Paramoloidose Hospital)	Dr. Coelho has nothing to disclose.
	No disclosure on file
	No disclosure on file
Marianne T. Sweetser, MD, PhD (Alnylam Pharmaceuticals)	Dr. Sweetser has received personal compensation for serving as an employee of Alnylam Pharmaceuticals. Dr. Sweetser has received stock or an ownership interest from Alnylam Pharmaceuticals.
	No disclosure on file
Jing Jing Wang, MD (Alexion Pharmaceutical Inc.)	No disclosure on file