Abstract Details

Title Evaluation of Glial Fibrillary Acidic Protein (GFAP) and Neurofilament Light Chain (NfL) Levels During Eculizumab and Ravulizumab Treatments in Aquaporin-4-Positive (AQP4+) Neuromyelitis Optica Spectrum Disorder (NMOSD)

Topic Autoimmune Neurology

Presentation(s) S32 - Autoimmune Neurology: NMOSD/MOGAD (1:36 PM-1:48 PM)

Poster/Presentation
Number 004

Background GFAP and NfL are biomarkers of astrocyte and neuronal injury, respectively. The placebo-controlled PREVENT (NCT01892345) and externally controlled CHAMPION-NMOSD (NCT04201262) trials evaluated the efficacy and safety of eculizumab and ravulizumab, respectively, in adults with AQP4+ NMOSD.

Objective Evaluate serum GFAP and NfL levels during treatment with complement component 5?inhibitor therapies (C5ITs) eculizumab and ravulizumab in AQP4+ NMOSD.

Design/Methods In PREVENT and CHAMPION-NMOSD, GFAP and NfL levels (pg/mL) were assessed using Quanterix's single-plex Simoa platforms at baseline, select study visits, and relapse visits. All relapses were independently adjudicated. External healthy donor (HD) samples were demographically matched for both trials.

Results

Median baseline serum GFAP levels were significantly elevated in AQP4+ NMOSD patients in each trial vs HDs (PREVENT: 123.0 [n=41] vs 89.2 [n=45], P=0.0007; CHAMPION-NMOSD: 129.0 [n=55] vs 89.2, P<0.0001), as were serum NfL levels (10.8 [n=41] vs 8.5 [n=47], P=0.0238; 9.8 [n=55] vs 8.5, P=0.0162). During adjudicated on-trial relapses in PREVENT, eculizumab reduced mean fold change (FC) GFAP from baseline (2.7-FC [n=3]) vs placebo (8.7-FC [n=7]). In PREVENT, median GFAP levels remained elevated with placebo (n=15) but were significantly diminished from baseline at week (W) 4 (P=0.0068) with eculizumab (n=26), and median values continued to appear low at W24; NfL levels appeared unchanged (placebo and eculizumab). In CHAMPION-NMOSD, GFAP and NfL median levels were significantly reduced from baseline with ravulizumab at W6 (P=0.0325 and P=0.0441; n=55), respectively, and levels appeared to decrease through W130. Median GFAP levels declined faster with ravulizumab than median NfL levels. Ravulizumab reduced NfL levels similarly in cerebrospinal fluid and serum.

Conclusions Decreasing serum GFAP and NfL levels over time suggest sustained reduction in damage to astrocytes and neurons in AQP4+ NMOSD, respectively, strengthening their suitability as potential biomarkers of therapeutic efficacy in AQP4+ NMOSD. Analyses of potential associations to patients’ clinical profiles are warranted.

Authors/Disclosures
Dean M. Wingerchuk, MD, FAAN (Mayo Clinic) PRESENTER	Dr. Wingerchuk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Imcyse. Dr. Wingerchuk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Wingerchuk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TTY Biopharm. Dr. Wingerchuk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Reistone Biopharm. Dr. Wingerchuk has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon Therapeutics. Dr. Wingerchuk has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Wingerchuk 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. Wingerchuk 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. Wingerchuk has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bristol Meyer Squibb. Dr. Wingerchuk has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB Pharma. Dr. Wingerchuk has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AstraZeneca. Dr. Wingerchuk has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Wingerchuk has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abcuro. Dr. Wingerchuk has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Wolters Kluwers.
Jeffrey L. Bennett, MD, PhD, FAAN (University of Colorado School of Medicine)	Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Horizon Therapeutics. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Alexion. Dr. Bennett has received personal compensation in the range of $0-$499 for serving as a Consultant for Genentech. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Chugai. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi Tanabe. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ImCyse. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Beigene. Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alexion. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Pavich. The institution of Dr. Bennett has received research support from Alexion. Dr. Bennett has received intellectual property interests from a discovery or technology relating to health care. Dr. Bennett has received publishing royalties from a publication relating to health care.
Achim Berthele (School of Medicine, Technical University Munich, Klinikum rechts der Isar, Dept.)	Achim Berthele has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Achim Berthele has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bayer. Achim Berthele has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Celgene. Achim Berthele has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Achim Berthele has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Achim Berthele has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Achim Berthele has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Achim Berthele has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Achim Berthele has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion.
Stacey Clardy, MD, PhD, FAAN (University of Utah)	Dr. Clardy has received personal compensation for serving as an employee of Veterans Health Administration (VHA). Dr. Clardy has received personal compensation for serving as an employee of University of Utah Health. Dr. Clardy has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AstraZeneca/Alexion. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amgen/Horizon. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Arialys. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Kyverna. Dr. Clardy has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology/AAN Publications. The institution of Dr. Clardy has received research support from NIH/NINDS. The institution of Dr. Clardy has received research support from SRNA. The institution of Dr. Clardy has received research support from Alexion/AstraZeneca. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a AAN Summer Meeting CoDirector Travel and Lodging with AAN. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a Grand Rounds Travel/Lodging/Honoraria with U of Iowa, Miami, Stanford, Barrow, Beaumont Health, CCF, Emory, Penn State, Mayo Clinic, Walter Reed.
Ho Jin Kim, MD (National Cancer Center)	Dr. Kim has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Aprilbio, HanAll BioPharma, Viela Bio. Dr. Kim has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion, Biogen, Celltrion, Eisai, Merck Serono, Novartis, Sanofi Genzyme, Teva-Handok. Dr. Kim has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Multiple Sclerosis Journal, Journal of Clinical Neurology.
Jin Nakahara, MD, PhD (Keio University School of Medicine)	Prof. Nakahara has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Prof. Nakahara has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Mitsubishi-Tanabe. Prof. Nakahara has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Prof. Nakahara has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Chugai. Prof. Nakahara has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Novartis. Prof. Nakahara has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen. Prof. Nakahara has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alexion. Prof. Nakahara has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Chugai. Prof. Nakahara has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Mitsubishi-Tanabe. Prof. Nakahara has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Takeda. Prof. Nakahara has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Daiichi-Sankyo. Prof. Nakahara has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Prof. Nakahara has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB. Prof. Nakahara has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for CSL Behring. Prof. Nakahara has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eisai. Prof. Nakahara has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for The Japanese Society for Internal Medicine. The institution of Prof. Nakahara has received research support from EA Pharma. The institution of Prof. Nakahara has received research support from JB. The institution of Prof. Nakahara has received research support from Eisai. The institution of Prof. Nakahara has received research support from Shionogi. The institution of Prof. Nakahara has received research support from Boehringer Ingelheim. The institution of Prof. Nakahara has received research support from Kyowa Kirin. The institution of Prof. Nakahara has received research support from Sumitomo Pharma. The institution of Prof. Nakahara has received research support from Otsuka. The institution of Prof. Nakahara has received research support from Chugai. The institution of Prof. Nakahara has received research support from Teijin. The institution of Prof. Nakahara has received research support from Mitsubishi-Tanabe.
Jerome De Seze	Jerome De Seze has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pharma. Jerome De Seze has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pharma. Jerome De Seze has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pharma. Jerome De Seze has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pharma. Jerome De Seze has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pharma. Jerome De Seze has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pharma. Jerome De Seze has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pharma. Jerome De Seze has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pharma.
Makoto Kinoshita, MD, PhD (Osaka University)	Dr. Kinoshita has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Kinoshita has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Kinoshita has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Chugai. Dr. Kinoshita has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for CSL Behring. Dr. Kinoshita has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Daiichi Sankyo. Dr. Kinoshita has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Mitsubishi Tanabe Pharma. Dr. Kinoshita has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. The institution of Dr. Kinoshita has received research support from Grants-in-Aid for Scientific Research. The institution of Dr. Kinoshita has received research support from JST Moonshot R and D program.
Ruba D. Bou-Chahine (Alexion Astrazeneca Rare Disease)	No disclosure on file
Yasmin Mashhoon, PhD (Alexion, AstraZeneca Rare Disease)	Dr. Mashhoon has received personal compensation for serving as an employee of Alexion, AstraZeneca Rare Disease . Dr. Mashhoon has stock in AstraZeneca.
Becky J. Parks, MD (Blueprint Medicines)	Dr. Parks has received personal compensation for serving as an employee of Alexion Pharmaceuticals. Dr. Parks has stock in Biogen. Dr. Parks has stock in Illumina. An immediate family member of Dr. Parks has stock in Regeneron. Dr. Parks has stock in Blueprint Medicines. Dr. Parks has stock in Sanofi. An immediate family member of Dr. Parks has stock in Vertex. Dr. Parks has stock in AstraZeneca. The institution of an immediate family member of Dr. Parks has received research support from NIH/NCI. The institution of an immediate family member of Dr. Parks has received research support from Leukemia & Lymphoma Society. The institution of an immediate family member of Dr. Parks has received research support from AstraZeneca Scholar Award.
Kerstin Allen	No disclosure on file
Ketan Thakar (Alexion Pharmaceuticals Inc.)	No disclosure on file
Dan Carlin (Alexion, AstraZeneca Rare Disease)	No disclosure on file
Jeannette Stankowski, PhD (Alexion)	Dr. Stankowski has nothing to disclose.
Sean J. Pittock, MD (Mayo Clinic Dept of Neurology)	Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech, Inc.. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sage Therapeutics, Inc.. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astellas. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Prime Therapeutics. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche/Genentech. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MedImmune/Viela Bio. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arialys Therapeutics. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche/Genentech. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB, Inc. Dr. Pittock has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hoffman/LaRoche AG. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genetech. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for F. Hofman/LaRoche. The institution of Dr. Pittock has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Arialys. The institution of Dr. Pittock has received research support from Grifols. The institution of Dr. Pittock has received research support from NIH. The institution of Dr. Pittock has received research support from Viela Bio/MedImmune/Horizon. The institution of Dr. Pittock has received research support from Alexion Pharmaceuticals. The institution of Dr. Pittock has received research support from F. Hoffman/LaRoche/Genentech. The institution of Dr. Pittock has received research support from NovelMed. The institution of Dr. Pittock has received research support from AstaZeneca. Dr. Pittock has received intellectual property interests from a discovery or technology relating to health care. Dr. Pittock has received intellectual property interests from a discovery or technology relating to health care. Dr. Pittock has received publishing royalties from a publication relating to health care.