Abstract Details

Title Plasma Phosphorylated Neurofilament Heavy Chain Levels Over Time in Participants With Infantile- and Later-onset SMA: Data from the SHINE Study

Topic General Neurology

Presentation(s) S57 - General Neurology: Diagnostic Testing and Disease Biomarkers (4:42 PM-4:54 PM)

Poster/Presentation
Number 007

Objective To investigate change in plasma phosphorylated neurofilament heavy chain (pNF-H) levels over time in nusinersen trial participants with infantile- or later-onset SMA.

Background NFs are neuronal cytoskeleton components released into interstitial fluid following axonal damage/neuronal degeneration. Elevated NF levels have been detected in neurodegenerative disorders.

Design/Methods Individuals treated with nusinersen or sham-procedure in the Phase 3 ENDEAR and CHERISH studies could transition to the open-label SHINE extension study (NCT02594124). Plasma pNF-H levels were measured at baseline and predose using the ProteinSimple pNF-H ELLA assay.

Results In participants who initiated nusinersen in ENDEAR and continued in SHINE (n=76), the geometric mean (±SD) plasma pNF-H concentration was 14,388 (8326) pg/ml at nusinersen initiation (ENDEAR baseline) and declined to 1261 (993) pg/ml at Day 302 (n=51; 15 October 2018 SHINE data cut). In those who received sham-procedure in ENDEAR and initiated nusinersen in SHINE (n=20), the geometric mean pNF-H concentration was 7556 (6265) pg/ml at nusinersen initiation (SHINE baseline) and declined to 778 (653) pg/ml at Day 183 (n=13). In participants who received nusinersen in CHERISH and SHINE (n=83), the geometric mean plasma pNF-H concentration was 1297 (1261) pg/ml at CHERISH baseline and declined to 439 (374) pg/ml at Day 450 (n=79). In the CHERISH sham-procedure group who initiated nusinersen in SHINE (n=32), the geometric mean pNF-H concentration was 746 (676) pg/ml at SHINE baseline and declined to 382 (204) pg/ml at Day 253 (n=8). Values for later timepoints and the SHINE 2019 data cut will be presented.

Conclusions

Plasma pNF-H levels at treatment initiation were higher in participants who initiated nusinersen in ENDEAR or CHERISH (compared with SHINE), consistent with differences attributable to age at treatment initiation and SMA disease characteristics. However, these data demonstrate a similar decline in pNF-H levels over time in nusinersen-treated participants, irrespective of when treatment was initiated.

Study supported by: Biogen

Authors/Disclosures
Basil T. Darras, MD (Children'S Hosp Boston Harvard Med School) PRESENTER	The institution of Dr. Darras has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amicus. Dr. Darras has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Amicus. The institution of Dr. Darras has received research support from National Institutes of Health/National Institute of Neurological Disorders and Stroke,. The institution of Dr. Darras has received research support from Slaney Family Fund for SMA. The institution of Dr. Darras has received research support from Spinal Muscular Atrophy Foundation. The institution of Dr. Darras has received research support from CureSMA. The institution of Dr. Darras has received research support from Working on Walking Fund . The institution of Dr. Darras has received research support from CHERISH, CS2/CS12 . The institution of Dr. Darras has received research support from Biogen for CS11. The institution of Dr. Darras has received research support from AveXis. The institution of Dr. Darras has received research support from Sarepta Pharmaceuticals. The institution of Dr. Darras has received research support from PTC Therapeutics. The institution of Dr. Darras has received research support from Roche. The institution of Dr. Darras has received research support from Santhera. The institution of Dr. Darras has received research support from Scholar Rock. The institution of Dr. Darras has received research support from Fibrogen. The institution of Dr. Darras has received research support from Summit. Dr. Darras has received publishing royalties from a publication relating to health care. Dr. Darras has received publishing royalties from a publication relating to health care.
Charlotte J. Sumner, MD, FAAN	Dr. Sumner has received personal compensation for serving as an employee of Biogen. Dr. Sumner has received personal compensation for serving as an employee of Avexis. Dr. Sumner has received personal compensation for serving as an employee of Roche/Genentech. Dr. Sumner has received personal compensation for serving as an employee of Ionis Pharmaceuticals. Dr. Sumner has received personal compensation for serving as an employee of Sarepta. Dr. Sumner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Sumner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avexis/Novartis. Dr. Sumner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche/Genentech. Dr. Sumner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sarepta. Dr. Sumner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alnylam. Dr. Sumner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Proneurotech. Dr. Sumner has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for CMTRF. Dr. Sumner has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Journal Clinical Investigation. Dr. Sumner has received research support from Roche. Dr. Sumner has received intellectual property interests from a discovery or technology relating to health care. Dr. Sumner has received publishing royalties from a publication relating to health care.
Francesco Muntoni, MD (UCL Institute of Child Health)	Dr. Muntoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sarepta. Dr. Muntoni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pfizer. Dr. Muntoni has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sarepta. Dr. Muntoni has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Biogen. Dr. Muntoni has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Muntoni has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. The institution of Dr. Muntoni has received research support from European Commission. The institution of Dr. Muntoni has received research support from Medical Research Council. The institution of Dr. Muntoni has received research support from Biogen. The institution of Dr. Muntoni has received research support from Muscular Dystrophy UK. The institution of Dr. Muntoni has received research support from MDA USA. The institution of Dr. Muntoni has received research support from Sarepta. The institution of Dr. Muntoni has received research support from Association Francoise Myopathies. Dr. Muntoni has received personal compensation in the range of $0-$499 for serving as a Clinical expert with UK NICE Committee.
Thomas O. Crawford, MD (Johns Hopkins Hospital)	Dr. Crawford has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen.
Richard S. Finkel, MD, FAAN (St. Jude Children's Research Hospital)	Dr. Finkel has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AveXis. Dr. Finkel has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Finkel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Catabasis. Dr. Finkel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Capricor. Dr. Finkel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ReveraGen. Dr. Finkel has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Finkel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Scholar Rock. Dr. Finkel has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. The institution of Dr. Finkel has received research support from AveXis. The institution of Dr. Finkel has received research support from Biogen. The institution of Dr. Finkel has received research support from Capricor. The institution of Dr. Finkel has received research support from Catabasis. The institution of Dr. Finkel has received research support from ReveraGen. The institution of Dr. Finkel has received research support from Roche. The institution of Dr. Finkel has received research support from Scholar Rock. Dr. Finkel has received intellectual property interests from a discovery or technology relating to health care. An immediate family member of Dr. Finkel has received intellectual property interests from a discovery or technology relating to health care. Dr. Finkel has received personal compensation in the range of $0-$499 for serving as a Speaker in workshop with National Academy of Sciences. Dr. Finkel has a non-compensated relationship as a advisor with n-Lorem Foundation that is relevant to AAN interests or activities. Dr. Finkel has a non-compensated relationship as a Board Member with EveryLife Foundation that is relevant to AAN interests or activities.
	No disclosure on file
Maryam Oskoui, MD, FAAN (Montreal Children's Hospital - McGill University Health Centre)	Dr. Oskoui has received personal compensation in the range of $500-$4,999 for serving as an officer or member of the Board of Directors for the Association des Neurologues du Quebec. The institution of Dr. Oskoui has received research support from Hoffmann-La Roche Ltd. The institution of Dr. Oskoui has received research support from Muscular Dystrophy Canada. The institution of Dr. Oskoui has received research support from Canadian Institutes of Health Research. The institution of Dr. Oskoui has received research support from Santhera. The institution of Dr. Oskoui has received research support from Novartis. Dr. Oskoui has a non-compensated relationship as a Member of the Medical and Scientific Advisory Committee with Muscular Dystrophy Canada that is relevant to AAN interests or activities.
	No disclosure on file
Monique M. Ryan, MD (Childrens Hospital)	Dr. Ryan has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen . Dr. Ryan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for CSL Behring . Dr. Ryan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Ryan has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen . The institution of Dr. Ryan has received research support from Save our Sons Muscular Dystrophy . The institution of Dr. Ryan has received research support from Muscular Dystrophy Australia. Dr. Ryan has received publishing royalties from a publication relating to health care.
Ying Liu	No disclosure on file
	No disclosure on file
Boris Kandinov	No disclosure on file
Janice Wong, MD	Dr. Wong has received personal compensation for serving as an employee of Janssen Research & Development. Dr. Wong has received personal compensation for serving as an employee of Biogen. Dr. Wong has stock in Biogen. Dr. Wong has stock in Janssen Research & Development.
Wildon Farwell, MD	Dr. Farwell has received personal compensation for serving as an employee of Biogen. Dr. Farwell has received stock or an ownership interest from Biogen.
Darryl C. De Vivo, MD, FAAN (Columbia University)	Dr. De Vivo has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen and Novartis. Dr. De Vivo has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Aspa Therapeutics.

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