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Abstract Details

Natalizumab versus placebo in patients with secondary progressive multiple sclerosis (SPMS): results from ASCEND, a multicenter, double-blind, placebo-controlled, randomized phase 3 clinical trial
Multiple Sclerosis
(-)
009
Natalizumab is highly efficacious in relapsing multiple sclerosis (RMS). However, no pharmacotherapeutics have been shown to reduce disability progression unrelated to relapses in SPMS patients.
ASCEND enrolled natalizumab-naive patients with SPMS for ≥2 years and disability progression unrelated to clinical relapses in the prior year. The primary endpoint (designed to capture treatment effects on key aspects of disability progression in SPMS) was a binary outcome of confirmed disability progressors or nonprogressors on a composite endpoint (Expanded Disability Status Scale [EDSS], Timed 25-Foot Walk [T25FW], and 9-Hole Peg Test [9HPT]).
Participants received 300-mg IV natalizumab (n=439) or placebo (n=448) every 4 weeks for 96 weeks. At baseline, most patients had advanced disability; 71% had no relapses within 2 years pre-enrollment. While 63% presented with EDSS scores of 6.0-6.5 (walking aid required), median 9HPT time was 28.6 seconds, suggesting greater lower-limb than upper-limb impairment. ASCEND did not meet the primary endpoint; a slightly smaller percent of patients treated with natalizumab were progressors (44%) compared with placebo (48%) [adjusted odds ratio [OR]: 0.86, 95% CI:0.66-1.13; P=0.29]. Natalizumab showed a statistically significant treatment effect on reducing upper-limb disability progression unrelated to relapse (measured by 9HPT, a pre-specified component of the primary endpoint; 15% natalizumab vs 23% placebo; OR: 0.56; P=0.0012). A significant treatment effect was also observed on reducing annualized relapse rate and MRI activity. Natalizumab was generally well tolerated, with adverse events consistent with its known safety profile.
While natalizumab did not delay progression of ambulatory disability in this SPMS population, it was associated with significant slowing of upper-extremity disability progression and reduction of relapses and MRI activity. The lack of treatment effects on ambulatory function underscores the importance of treating MS early with effective therapies like natalizumab.
Authors/Disclosures
Deborah Steiner, MD (Eli Lilly and Company) No disclosure on file
Douglas L. Arnold, MD, FAAN (Montreal Neurological Institute, McGill Univ) Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for BMS. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Frequency Therapeutics. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck. Dr. Arnold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Arnold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Shionogi. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Xfacto communications. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Find therapeutics. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GSK. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Idorsia. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kiniksa. Dr. Arnold has stock in NeuroRx.
Mark S. Freedman, MD, FAAN (University of Ottawa) Dr. Freedman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Actelion(Janssen/J&J). Dr. Freedman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BiogenIdec. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS/Celgene. Dr. Freedman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMD Inc. Dr. Freedman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Freedman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Actelion (Janssen/J&J). Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Atara Biotherapeutics. Dr. Freedman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Bayer Healthcare. Dr. Freedman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for BiogenIdec. Dr. Freedman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Clene Nanomedicine. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for GRI Bio. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Magenta Therapeutics. Dr. Freedman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck Serono. Dr. Freedman 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. Freedman has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi Genzyme. Dr. Freedman has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Sanofi Genzyme. Dr. Freedman has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for EMD Serono. The institution of Dr. Freedman has received research support from Sanofi Genzyme.
Myla D. Goldman, MD, MSc, FAAN (Virginia Commonwealth University) Dr. Goldman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMD Seronon. Dr. Goldman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen, IDEC. Dr. Goldman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genzyme. Dr. Goldman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentec. Dr. Goldman has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for ADAMAS. Dr. Goldman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Immunic. Dr. Goldman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis Pharmceuticals. Dr. Goldman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Greenwich Biosciences. Dr. Goldman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merk. Dr. Goldman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Brainstorm Cell Therapeutics Ltd., .
Hans-Peter Hartung, MD, FAAN (Heinrich Heine University Medical Faculty) Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS Celgene. Dr. Hartung has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Geneuro. Dr. Hartung has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Hartung 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. Hartung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Hartung has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bayer. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Frontiers Neurology.
Eva Havrdova, MD (Neurologicka Klinika 1 LF UK) Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi.
Douglas R. Jeffery, MD, PhD (Lake Norman Neurology At Piedmont Health Care) No disclosure on file
No disclosure on file
Aaron E. Miller, MD, FAAN (Mt Sinai School Of Med) Dr. Miller has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Accordant Health Services (Caremark). Dr. Miller has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Corevitas (formerly known as Corrona). Dr. Miller has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for MAPI=Pharma. Dr. Miller has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Viatris (Mylan). Dr. Miller has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Guidepoint Global. Dr. Miller has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gerson Lehrman Group. Dr. Miller has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen Idec. Dr. Miller has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Alexion. Dr. Miller has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Amgen (Horizon Therapeutics). Dr. Miller has received personal compensation in the range of $50,000-$99,999 for serving as an Expert Witness for Sterne Kessler. Dr. Miller has received publishing royalties from a publication relating to health care.
No disclosure on file
Diogo Amarante, MD No disclosure on file
Diego Cadavid, MD, FAAN (Verge Genomics) Dr. Cadavid has received personal compensation for serving as an employee of Verge Genomics. Dr. Cadavid has received personal compensation for serving as an employee of X4 Pharmaceuticals. Dr. Cadavid has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pheno Therapeutics. Dr. Cadavid has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novo Nordisk. Dr. Cadavid has stock in Verge Genomics.
No disclosure on file
No disclosure on file
No disclosure on file