Abstract Details

Title Treatment of PIRA with Nasal Foralumab Dampens Microglial Activation and Stabilizes Clinical Progression in Non-active Secondary Progressive MS

Topic Multiple Sclerosis

Presentation(s) S31 - Multiple Sclerosis: Therapeutics and Clinical Decision Making (1:12 PM-1:24 PM)

Poster/Presentation
Number 002

Background

A major unmet need in MS is developing therapy for na-SPMS with PIRA and smoldering inflammation. [F-18]PBR06 is a long half-life PET ligand targeting the 18kiloDalton translocator protein that measures microglial density and is increased in na-SPMS and PIRA. We are using nasal foralumab to treat MS subjects with PIRA in an open-label expanded-access program based on its positive effects in attenuating microglial activation and clinical progression in an animal model of progressive MS.

Objective To assess the effect of nasal foralumab, a fully-human anti-CD3 monoclonal-antibody on microglial activation in non-active secondary progressive multiple sclerosis (na-SPMS) with PIRA (progression independent of relapses).

Design/Methods

22 [F-18]PBR06-PET scans were performed in 6 na-SPMS patients with PIRA (3 females) who underwent [F-18]PBR06-PET scans at baseline and at 3 and 6 months following nasal foralumab treatment and in 2 na-SPMS patients with PIRA who underwent a test and a retest [F-18]PBR06-PET scan. A voxel-by-voxel z-score mapping approach was used and sum of z-scores in voxels with z-values>2 was calculated. Longitudinal PET uptake and clinical changes were assessed.

Results Five of six patients (83%, 95% confidence interval 44%-97%) showed a qualitative reduction on [F-18]PBR06-PET in multiple brain regions after both 3 and 6 months of nasal foralumab treatment. White matter z-scores were reduced by 26-36% in the foralumab treated group at 3 and 6 months, which was >4-5-times higher compared to 6% variability in the test-retest group (PET effect size estimate at 3 months=1.4). Clinically, foralumab-treated patients demonstrated a stable EDSS and improvement in the modified fatigue impact scale.

Conclusions

Nasal foralumab attenuated microglial activation in na-SPMS patients with PIRA at 3 and 6 months, as evaluated by [F-18]PBR06-PET and was associated with clinical stability. Based on these positive results, a double-blind, placebo-controlled dose-ranging study of nasal-foralumab in na-SPMS with [F-18]PBR06-PET as a primary endpoint is underway.

Authors/Disclosures
Tarun Singhal, MD (Brigham And Women's Hospital) PRESENTER	Dr. Singhal has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Singhal has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech . Dr. Singhal has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Singhal has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Singhal has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genzyme Sanofi. Dr. Singhal has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Tiziana LifeSciences. The institution of Dr. Singhal has received research support from Novartis. The institution of Dr. Singhal has received research support from Department of Defense. The institution of Dr. Singhal has received research support from Foundation for Neurologic Diseases.
Jonathan D. Zurawski, MD (Brigham & Women's Hospital)	The institution of Dr. Zurawski has received research support from The Race to Erase MS Foundation. The institution of Dr. Zurawski has received research support from Novartis Pharmaceuticals. The institution of Dr. Zurawski has received research support from I-Mab Biopharma . The institution of Dr. Zurawski has received research support from Elizabeth A. Kremer MS Research Foundation. The institution of Dr. Zurawski has received research support from Novartis.
Steven Cicero	No disclosure on file
Steven Vaquerano (Brigham and Women's Hospital)	No disclosure on file
Shipra Dubey	No disclosure on file
Taylor J. Saraceno (Brigham and Women'S Hospital)	Ms. Saraceno has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cumming Foundation. The institution of Ms. Saraceno has received research support from I-Mab Biopharma.
Danielle M. Howard, MD (Tufts Medical Center)	The institution of Dr. Howard has received research support from Genentech. The institution of Dr. Howard has received research support from Novartis. Dr. Howard has received personal compensation in the range of $50,000-$99,999 for serving as a Clinical Fellow with National Multiple Sclerosis Society.
John M. Sullivan, PA (Brigham & Women's Hospital)	Mr. Sullivan has received research support from Foundation for Neurologic Diseases.
Nancy Clementi (Clementi)	No disclosure on file
Howard L. Weiner, MD (Brigham and Women'S Hospital)	Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medday Pharmaceuticals. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for vTv Therapeutics. Dr. Weiner has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Tiziana Life Sciences. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for vTv Therapeutics. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Medday Pharmaceuticals. Dr. Weiner 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 vTv Therapeutics. Dr. Weiner has stock in vTv Therapeutics. The institution of Dr. Weiner has received research support from National Institute of Health. The institution of Dr. Weiner has received research support from National MS Society. The institution of Dr. Weiner has received research support from Genzyme Corp. The institution of Dr. Weiner has received research support from Genentech, Inc. . The institution of Dr. Weiner has received research support from Verily Life Sciences LLC. The institution of Dr. Weiner has received research support from EMD Serono, Inc..
Tanuja Chitnis, MD, FAAN (Brigham and Women's Hospital)	Dr. Chitnis has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Chitnis has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche-Genentech. Dr. Chitnis has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Siemens. Dr. Chitnis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Octave Biosciences. Dr. Chitnis has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Academic CME. The institution of Dr. Chitnis has received research support from Novartis. The institution of Dr. Chitnis has received research support from Sanofi. The institution of Dr. Chitnis has received research support from Octave. The institution of Dr. Chitnis has received research support from Genentech-Roche.