Abstract Details

Title Long-term Safety and Efficacy of Patisiran in Patients with hATTR Amyloidosis: Global OLE Study

Topic General Neurology

Presentation(s) S12 - General Neurology: Neurotherapeutics and Clinical Trials (4:42 PM-4:54 PM)

Poster/Presentation
Number 007

Objective Describe the interim 12-month safety and efficacy data (as of 09/24/2018) for patients in the ongoing Global Open-Label Extension (OLE) study.

Background Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive, life-threatening disease; majority of patients develop a mixed phenotype including polyneuropathy and cardiomyopathy. Patisiran’s efficacy and safety over 18-24 months have been demonstrated in Phase 2 and Phase 3 (APOLLO) studies in hATTR amyloidosis with polyneuropathy.

Design/Methods Multicenter, international, OLE, safety and efficacy 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 211 patients enrolled into Global OLE; 189 had 12-month assessments by September 24, 2018. Safety profile remained consistent with previous studies. After 12 months of additional patisiran treatment in 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 compared to parent study baselines. Norfolk QOL-DN (only measured at parent study baseline in APOLLO) showed durable improvement in APOLLO/patisiran patients (-3.9 [2.1]) following additional 12-months treatment. In the Global OLE, APOLLO/placebo patients experienced improvement on average after 12 months of patisiran (mNIS+7: -1.4 [2.4], Norfolk QOL-DN: -4.5 [2.5]), although they had progressed relative to APOLLO baseline (mNIS+7: +24.0 [4.2], Norfolk QOL-DN: +15.0 [3.4]) given the 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 or more. Overall, patients with longer-term exposure to patisiran demonstrated durability of effect. Despite marked progression on placebo during the 18-month APOLLO study, 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 compared to patients treated earlier with patisiran.

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.
	No disclosure on file
Teresa Coelho, MD (Unidate Clinica de Paramoloidose Hospital)	Dr. Coelho has nothing to disclose.
	No disclosure on file
	No disclosure on file
	No disclosure on file
John L. Berk	John L. Berk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alnylam Pharmaceuticals. John L. Berk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ionis Pharmaceuticals. John L. Berk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astra Zeneca/IONIS. John L. Berk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eidos/BridgBio. John L. Berk has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Intellia Therapeutics. John L. Berk has received research support from Alnylam . John L. Berk has received research support from Ionis. John L. Berk has received research support from Eidos/Bridgbio.
	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
	No disclosure on file

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