Abstract Details

Title Neurofilament Light Chain (NfL) as a Potential Biomarker of Treatment Response in Hereditary Transthyretin-Mediated Amyloidosis: Data from the Patisiran Global OLE Study

Topic General Neurology

Presentation(s) General Neurology Posters (7:00 AM-5:00 PM)

Poster/Presentation
Number 093

Objective Evaluate long-term change in neurofilament light chain (NfL) levels in response to patisiran in patients enrolled in the Global Open-Label Extension (OLE) study.

Background Hereditary transthyretin-mediated (hATTR) amyloidosis, also known as ATTRv amyloidosis, is a rare, rapidly progressing, fatal disease; majority of patients develop a mixed phenotype of polyneuropathy and cardiomyopathy. Patisiran is approved for the treatment of hATTR amyloidosis with polyneuropathy and its long-term efficacy/safety is being studied in a Global OLE. Plasma biomarkers, such as NfL, are being investigated for utility in facilitating earlier diagnosis of ATTRv amyloidosis and monitoring disease/treatment response.

Design/Methods NfL plasma levels were measured in duplicate in healthy controls and patients with ATTRv amyloidosis with polyneuropathy using the Quanterix Simoa platform. Patient samples were analyzed from the APOLLO study at baseline and 18 months in placebo and patisiran groups. NfL levels were also measured at 12 and 24 months following APOLLO in patients who rolled into the Global OLE.

Results NfL levels at APOLLO baseline were 63.2 (placebo) and 72.1 pg/mL (patisiran). NfL increased during APOLLO in the placebo group (99.5 pg/mL), whereas a significant decrease was observed at 18 months following patisiran (48.8 pg/mL). Reduced NfL levels were maintained in the APOLLO-patisiran group through 24 months of additional patisiran treatment in the Global OLE (44.0 pg/mL), consistent with maintained improvement in mNIS+7. Upon initiation of patisiran in the Global OLE, the APOLLO-placebo group experienced a reduction in NfL levels through 24 months (44.2 pg/mL), reaching a similar level to the APOLLO-patisiran group.

Conclusions NfL may serve as a biomarker of active nerve damage and polyneuropathy due to TTR amyloid deposition, making it useful as a potential biomarker of disease progression and treatment response. NfL levels may be useful for earlier diagnosis of polyneuropathy in patients with ATTRv amyloidosis and monitoring disease and treatment response over time.

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
	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.
Emre Aldinc	Emre Aldinc has received personal compensation for serving as an employee of Alnylam Pharmaceuticals. Emre Aldinc has stock in Alnylam Pharmaceuticals.
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.
Mary Reilly, MD, FRCP, FRCPI (National Hospital for Neurology and Neurosurgery)	The institution of Mary Reilly, MD, FRCP, FRCPI has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alynlam. Mary Reilly, MD, FRCP, FRCPI has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AKCEA. Mary Reilly, MD, FRCP, FRCPI has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Inflectis. The institution of Mary Reilly, MD, FRCP, FRCPI has received research support from MRC. The institution of Mary Reilly, MD, FRCP, FRCPI has received research support from NIH. The institution of Mary Reilly, MD, FRCP, FRCPI has received research support from MDA.
Akshay Vaishnaw (Alnylam)	Akshay Vaishnaw, 22867 has received personal compensation for serving as an employee of Alnylam Pharmaceuticals. Akshay Vaishnaw, 22867 has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Editas Medicine. Akshay Vaishnaw, 22867 has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Scholar Rock. Akshay Vaishnaw, 22867 has received stock or an ownership interest from Alnylam Pharmaceuticals.
	No disclosure on file

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