Abstract Details

Title Impact of Patisiran on Activities of Daily Living and Functional Status in hATTR Amyloidosis

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) S32 - Therapeutics of Genetic Neuromuscular Diseases (4:08 PM-4:16 PM)

Poster/Presentation
Number 002

Objective Analysis of the impact of patisiran on activities of daily living (ADLs) and functional status in the Phase 3 APOLLO study are presented here.

Background Hereditary transthyretin-mediated (hATTR) amyloidosis, a rare, multi-systemic, life-threatening disease, causes neurologic and cardiac dysfunction, leading to impaired functional status and declining ability to perform activities of daily living (ADLs). Analysis of the impact of patisiran on ADLs and functional status in the Phase 3 APOLLO study are presented here.

Design/Methods APOLLO was a randomized, placebo-controlled study of patisiran in patients with hATTR amyloidosis with polyneuropathy (NCT01960348). ADL/functional status assessments included: Rasch-built Overall Disability Scale (R-ODS), Karnofsky Performance Status (KPS), the ADL subdomain of Norfolk QOL-DN (Norfolk ADL). Post-hoc analyses quantified patients with no change/improvement in these assessments at 18 months.

Results

APOLLO enrolled 225 patients worldwide with a mean age of 60.5 years, 74% male, and 43% with V30M transthyretin mutation. At baseline, patisiran and placebo groups had similar R-ODS, KPS, and Norfolk ADL scores. After 18 months, a higher proportion of patisiran-treated patients experienced no change/improvement in functional status and ADLs relative to placebo: R-ODS 49.3% vs 13.0% (odds ratio [OR] 6.5, 95% confidence interval [CI] 2.8 to 15.4), KPS 64.9% vs 42.9%, (OR 2.5, 95% CI 1.3 to 4.8), Norfolk ADL 56.2% vs 20.4% (OR 5.0, 95% CI 2.4 to 10.5).

Conclusions In APOLLO, the largest randomized clinical study of patients with hATTR amyloidosis with polyneuropathy to date, patisiran preserved ability to perform ADLs and functional status for the majority of patients and demonstrated greater odds of stabilizing or improving these assessments compared to placebo.

Authors/Disclosures
Amanda C. Peltier, MD, MS (Vanderbilt University) PRESENTER	Dr. Peltier has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alnylam. Dr. Peltier has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for astrazeneca. Dr. Peltier has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for CSL Behring. Dr. Peltier has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Csl Behring. Dr. Peltier has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for argenx. Dr. Peltier has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for alnylam. Dr. Peltier has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for astrazeneca. Dr. Peltier has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Goldman Ismail. The institution of Dr. Peltier has received research support from NIH. The institution of Dr. Peltier has received research support from CSL Behring.
	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
Ole Suhr	The institution of Ole Suhr has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alnylam . The institution of Ole Suhr has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Akcea. The institution of Ole Suhr has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Prothena. The institution of Ole Suhr has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Intellia. The institution of Ole Suhr has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Akces. The institution of Ole Suhr has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alnylam. Ole Suhr has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alnylam. Ole Suhr has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Akcea. The institution of Ole Suhr has received research support from Swedish Heart and Lung Foundation.
Senda Ajroud-Driss, MD, FAAN (Northwestern University)	Dr. Ajroud-Driss has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Ajroud-Driss has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Astrazeneca. Dr. Ajroud-Driss has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. The institution of Dr. Ajroud-Driss has received research support from NIH. The institution of Dr. Ajroud-Driss has received research support from University of Minesota/FDA. The institution of Dr. Ajroud-Driss has received research support from Edgewise Therapeutics. The institution of Dr. Ajroud-Driss has received research support from Biogen. The institution of Dr. Ajroud-Driss has received research support from Woolsey Pharmaceuticals. The institution of Dr. Ajroud-Driss has received research support from Uniqure Biopharma. The institution of Dr. Ajroud-Driss has received research support from Coya Therapeutics. The institution of Dr. Ajroud-Driss has received research support from Novartis. The institution of Dr. Ajroud-Driss has received research support from Alnylam pharmaceuticals. The institution of Dr. Ajroud-Driss has received research support from Healey and AMG center for ALS . The institution of Dr. Ajroud-Driss has received research support from les Turner ALS Foundation. The institution of Dr. Ajroud-Driss has received research support from Hopewell. The institution of Dr. Ajroud-Driss has received research support from Peripheral neuropathy foundation. Dr. Ajroud-Driss has received publishing royalties from a publication relating to health care.
Madeline Merkel	Madeline Merkel has received personal compensation for serving as an employee of Alnylam Pharmaceuticals.
	No disclosure on file
	No disclosure on file
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.

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