Abstract Details

Title Ofatumumab Reduces Disability Progression Independent of Relapse Activity in Patients with Relapsing Multiple Sclerosis

Topic Multiple Sclerosis

Presentation(s) S40 - Multiple Sclerosis: Clinical Trials (1:36 PM-1:48 PM)

Poster/Presentation
Number 004

Objective

To assess the effect of ofatumumab versus teriflunomide on confirmed disability Progression Independent of Relapse Activity (PIRA).

Background

Ofatumumab, the first fully human anti-CD20 monoclonal antibody with a monthly low-dose (20 mg, s.c.) regimen, showed superior efficacy versus teriflunomide in the Phase 3 ASCLEPIOS I and II trials in relapsing multiple sclerosis (RMS) patients. As RMS patients acquire disability due to incomplete recovery from relapses or through gradual disability progression, it is important to characterize treatment effect on PIRA.

Design/Methods

In this pooled analysis of the ASCLEPIOS I and II trials, the risk of disability progression confirmed at 3-/6-months (3mCDP/6mCDP: Expanded Disability Status Scale [EDSS] score increase of ≥1.0 if baseline EDSS score <6, or ≥0.5 if baseline EDSS score ≥6) was evaluated in three subsets of patients: (A) without confirmed relapses during the study; (B) without confirmed relapses prior to a 3mCDP/6mCDP event; (C) with secondary progressive multiple sclerosis diagnosis at study-entry and without confirmed relapses during the study. Hazard ratios (HRs) and p-values were calculated by a Cox-regression model adjusted for study as stratum, for treatment, region, and baseline EDSS score as covariates. An inversed probability censor weighted (IPCW) analysis, censoring patients with confirmed relapses prior to a 3mCDP/6mCDP event, was also performed.

Results

Ofatumumab significantly reduced the risk of 3mCDP and 6mCDP (vs. teriflunomide) in all subsets analyzed except for 6mCDP in Subset-C: Subset-A by 41.3% (HR [95%CI]: 0.587 [0.407?0.848], p=0.004) and 36.8% (0.632 [0.421?0.947], p=0.026); Subset-B by 48.4% (0.516 [0.365?0.729], p<0.001) and 44.9% (0.551 [0.377?0.805], p=0.002); and Subset-C by 68.8% (0.312 [0.114?0.859], p=0.024) and 53.7% (0.463 [0.158?1.355], p=0.160). IPCW estimation of PIRA, confirmed risk reduction for 3mCDP (46.0%: 0.540 [0.396?0.738], p<0.001) and 6mCDP (42.5%: 0.575 [0.409?0.808], p=0.001) versus teriflunomide.

Conclusions

When compared with teriflunomide, ofatumumab markedly reduced disability progression independent of relapses in a RMS population.

Authors/Disclosures
Xavier Montalban, MD, PhD, FAAN (Vall Hebron University Hospital-Multiple Sclerosis Centre of Catalonia) PRESENTER	The institution of Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. The institution of Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Merck/ EMD Serono. The institution of Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. The institution of Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Teva. The institution of Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Hoffmann-La Roche. The institution of Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Actelion/ Janssen Pharmaceuticals. The institution of Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for BMS/ Celgene. The institution of Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi/ Genzyme. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BIAL PD. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving as a Consultant for PeerVoice. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Samsung Biosys. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Zenas BioPharma. Dr. Montalban has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Actelion/ Janssen Pharmaceuticals. Dr. Montalban 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. Montalban has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BMS/ Celgene. Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck/ EMD Serono. Dr. Montalban 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. Montalban has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hoffmann-La Roche. Dr. Montalban has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi-Genzyme. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Immunic Therapeutics. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Viatris/ Mylan. The institution of Dr. Montalban has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sandoz. The institution of Dr. Montalban has received research support from Biogen. The institution of Dr. Montalban has received research support from Hoffmann-La Roche. The institution of Dr. Montalban has received research support from Sanofi/ Genzyme. The institution of Dr. Montalban has received research support from Merck/ EMD Serono. The institution of Dr. Montalban has received research support from Novartis. The institution of Dr. Montalban has received research support from Teva Pharmaceuticals. The institution of Dr. Montalban has received research support from Actelion/ Janssen Pharmaceuticals. The institution of Dr. Montalban has received research support from BMS/ Celgene.
Jeffrey A. Cohen, MD (Cleveland Clinic)	Dr. Cohen has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Convelo. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astoria. Dr. Cohen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Viatris. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for PSI. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Shionogi. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Celltrion.
	No disclosure on file
Patricia K. Coyle, MD, FAAN (SUNY At Stony Brook)	Dr. Coyle has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Accordant. Dr. Coyle has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amgen. Dr. Coyle has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Sanofi Genzyme. Dr. Coyle has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Coyle has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for GlaxoSmithKline. Dr. Coyle has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Horizon Therapeutics. The institution of Dr. Coyle has received research support from CorEvitas LLC. The institution of Dr. Coyle has received research support from Genentech/Roche. The institution of Dr. Coyle has received research support from NINDS. The institution of Dr. Coyle has received research support from Sanofi Genzyme. The institution of Dr. Coyle has received research support from Cleveland Clinic.
Ludwig Kappos, MD, FAAN (RC2NB, University Hospital Basel)	Dr. Kappos has nothing to disclose.
Bingbing Li	Bingbing Li has received personal compensation for serving as an employee of Novartis.
Nicolaos Sfikas (Novartis Pharma AG)	No disclosure on file
Roman Willi, PhD (Novartis Pharma AG)	Dr. Willi has received personal compensation for serving as an employee of Novartis Pharma. Dr. Willi has received stock or an ownership interest from Novartis.
Dieter Haering	Dieter Haering has received personal compensation for serving as an employee of Novartis.
Martin Merschhemke	No disclosure on file
Stephen L. Hauser, MD (UCSF Weill Institute for Neurosciences)	Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NGM Bio. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Moderna. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BD. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pheno Therapeutics. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nurix Therapeutics. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gilead. Dr. Hauser has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Accure. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alector. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hinge Therapeutics. Dr. Hauser 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 Neurona. Dr. Hauser has a non-compensated relationship as a Clinical Trial/Primary Investigator with Roche that is relevant to AAN interests or activities. Dr. Hauser has a non-compensated relationship as a Clinical Trial/Primary Investigator with Novartis that is relevant to AAN interests or activities.

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