Abstract Details

Title Impact of Patisiran on Overall Health Status in hATTR Amyloidosis: Results from the APOLLO Trial

Topic General Neurology

Presentation(s) S27 - General Neurology: Improving Neurologic Care and the Impact of Therapeutics (2:06 PM-2:17 PM)

Poster/Presentation
Number 007

Background

Hereditary transthyretin-mediated (hATTR) amyloidosis is a multisystem, life-threatening disease resulting in heterogenous manifestations including neuropathy and cardiomyopathy, significantly impacting quality of life (QoL). In the Phase 3 APOLLO study, patisiran, an investigational RNAi therapeutic for hATTR amyloidosis, resulted in significant improvement in neuropathy and QoL (measured by Norfolk QoL-DN), and was generally well-tolerated.

Objective Here, we further evaluate the impact of patisiran on overall health in patients enrolled in APOLLO.

Design/Methods

APOLLO was a randomized (2:1), double-blind, placebo-controlled study of patisiran 0.3 mg/kg or placebo IV q3W in hATTR amyloidosis patients with polyneuropathy (NCT01960348). Overall health status was an exploratory endpoint assessed using EuroQOL-5-dimension 5-level (EQ-5D-5L), a standardized measure of health status based on 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, and the EuroQoL visual analogue scale (EQ-VAS), a patient’s global impression of their overall health. Preservation was defined as no change in score.

Results APOLLO enrolled 225 patients: mean age 60.5-years (24-83), 74% males and 43% with V30M mutation. At 18 months, the patisiran group showed overall improvement in health status assessed by EQ-5D index scores and EQ-VAS, compared to the placebo group; improvement was observed as early as 9 months. A larger proportion of patients on patisiran than placebo, respectively, showed preservation or improvement relative to baseline in each domain: mobility, 70% vs 22%; self-care, 66% vs 21%; usual activities, 72% vs 25%; pain/discomfort, 73% vs 31%; anxiety/depression, 81% vs 45%. While overall health, EQ-VAS, improved (increased by average 2.4 points) in patients on patisiran, overall health in patients on placebo declined by average of 7.1 points, indicating a 9.5 point difference (p=0.0004).

Conclusions Patisiran improved overall health status as measured by EQ-5D-5L in a manner similar to Norfolk QoL-DN, showing an improvement in overall health status compared to placebo in patients with hATTR amyloidosis.

Authors/Disclosures
Senda Ajroud-Driss, MD, FAAN (Northwestern University) PRESENTER	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 Amylyx Pharmaceuticals. 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. The institution of Dr. Ajroud-Driss has received research support from ALSA. Dr. Ajroud-Driss has received publishing royalties from a publication relating to health care.
	No disclosure on file
Teresa Coelho, MD (Unidate Clinica de Paramoloidose Hospital)	Dr. Coelho has nothing to disclose.
Michael J. Polydefkis, MD, FAAN (Johns Hopkins University School of Medicine)	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
Dianna Quan, MD, FAAN (University of Colorado School of Medicine)	The institution of Dr. Quan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alnylam. The institution of Dr. Quan has received research support from Alnylam. The institution of Dr. Quan has received research support from Pfizer. The institution of Dr. Quan has received research support from Cytokinetics. The institution of Dr. Quan has received research support from Argenx. The institution of Dr. Quan has received research support from Momenta. The institution of Dr. Quan has received research support from Ionis. The institution of Dr. Quan has received research support from Alexion. The institution of Dr. Quan has received research support from VielaBio. The institution of Dr. Quan has received research support from Apellis. The institution of Dr. Quan has received research support from Avidity. Dr. Quan has received publishing royalties from a publication relating to health care. Dr. Quan has received publishing royalties from a publication relating to health care. Dr. Quan has a non-compensated relationship as a Board Member/President with AANEM that is relevant to AAN interests or activities.
	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.
Annie Partisano	No disclosure on file
Jared Gollob, MD (Alnylam Pharmaceuticals)	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
	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.

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