Abstract Details

Title Identifying Mixed Phenotype: Evaluating the Presence of Polyneuropathy in Patients with Hereditary Transthyretin-Mediated Amyloidosis with Cardiomyopathy

Topic General Neurology

Presentation(s) S57 - General Neurology: Diagnostic Testing and Disease Biomarkers (3:54 PM-4:06 PM)

Poster/Presentation
Number 003

Objective To describe the presence of polyneuropathy signs and symptoms in patients with hATTR amyloidosis and confirmed cardiomyopathy to evaluate prevalence of mixed phenotype presentation among these patients.

Background Hereditary transthyretin-mediated (hATTR) amyloidosis is an inherited, progressively debilitating, fatal disease caused by amyloid accumulation in tissues and organs. Historically, patients were grouped by their predominant phenotype: cardiomyopathy or polyneuropathy. However, recent studies have shown that the majority of patients develop a mixed phenotype of polyneuropathy and cardiomyopathy.

Design/Methods Patients enrolled in the Phase 3 ENDEAVOUR study had hATTR amyloidosis with cardiomyopathy (n=206) with a documented TTR mutation, amyloid deposition by biopsy or technetium (^99mTc) scintigraphy, echocardiographic evidence of cardiac amyloid involvement, and medical history or clinical evidence of heart failure. Baseline disease characteristics and medical history were analyzed in the overall group and by genotype to identify the presence of polyneuropathy signs and symptoms.

Results The 3 most common genotypes in the Phase 3 study included Val122Ile (n=118), Thr60Ala (n=35), and Val30Met (n=9). Majority of patients had symptomatic heart failure at baseline (61% NYHA Class II and 31% Class III) and medical history of heart failure (85%). By Polyneuropathy Disability (PND) Score at enrollment, symptoms of polyneuropathy were present in the majority of patients; 53% of patients had sensory abnormalities (PND I) or sensorimotor impairment affecting ambulation (PND II). Based on medical history, 54% of patients had a diagnosis that coded to the nervous system disorders based on peripheral neuropathy standard MedDRA query (49% of Val122Ile patients, 66% Thr60Ala patients, and 78% Val30Met patients).

Conclusions hATTR amyloidosis is a debilitating disease with variable genotype-phenotype relationship. In patients with hATTR amyloidosis with cardiomyopathy, signs and symptoms of polyneuropathy were common. The mixed presentation of hATTR amyloidosis highlights the importance of multisystem disease assessment in this patient population.

Authors/Disclosures
Madeline Merkel PRESENTER	Madeline Merkel has received personal compensation for serving as an employee of Alnylam Pharmaceuticals.
	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.
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.
	No disclosure on file
Anastasia McManus	Anastasia McManus has received personal compensation for serving as an employee of Alnylam Pharmaceuticals. Anastasia McManus has received stock or an ownership interest from Alnylam Pharmaceuticals.
	No disclosure on file
John Vest	John Vest has received personal compensation for serving as an employee of Alnylam Pharmaceuticals. John Vest has received stock or an ownership interest from Alnylam Pharmaceuticals. John Vest has received intellectual property interests from a discovery or technology relating to health care.
	No disclosure on file
	No disclosure on file

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