Ofatumumab, Novartis’s fully human anti-CD20 monoclonal antibody, demonstrated a reduction in the risk of 3- and 6-month confirmed disability progression compared to teriflunomide in relapsing multiple sclerosis.
Xavier Montalban, MD, PhD
New comparative data on ofatumumab, Novartis’ first fully human anti-CD20 monoclonal antibody with a monthly low-dose (20 mg) regimen, suggest that the therapy is superior in efficacy compared to teriflunomide (Aubagio; Sanofi) in treating patients with relapsing multiple sclerosis (MS).1
The data, which were accepted for presentation at the American Academy of Neurology (AAN) 2020 Annual Meeting, used pooled analysis from the phase 3 ASCLEPIOS I and II trials and suggest that ofatumumab significantly reduced the risk of 3- and 6-month confirmed disability progression (CDP) compared to teriflunomide, save for in a single subgroup of patients, Subset C.
With regard to 3-month CDP, patients in Subset A experienced a risk reduction of 41.3% (hazard ratio [HR], 0.587; 95% CI, 0.407—0.848; P = .004) compared to those treated with teriflunomide. Those in Subset B and Subset C reported risk reductions of 48.4% (HR, 0.516; 95% CI, 0.365—0.729; P <.001) and 68.8% (HR, 0.312; 95% CI, 0.114—0.859; P = .024), respectively, in comparison.
Similarly, for 6-month CDP, those administered ofatumumab experienced risk reductions of 36.8% (HR, 0.632; 95% CI, 0.421—0.947; P = .026) in Subset A, 44.9% (HR, 0.551; 95% CI, 0.377—0.805; P = .002) in Subset B, and 53.7% (HR, 0.463; 95% CI, 0.158—1.355; P = .160) in Subset C.
Study author Xavier Montalban, MD, PhD, professor of medicine, and Department Division Director, Neurology, University of Toronto, and colleagues noted that “as relapsing MS patients acquire disability due to incomplete recovery from relapses or through gradual disability progression, it is important to characterize treatment effect on Progression Independent of Relapse Activity [PIRA].” Inversed probability censor weighted estimation of PIRA suggested that confirmed risk reduction for 3-month CDP was 46.0% (HR, 0.540; 95% CI, 0.396—0.738; P <.001) and for 6-month CDP was 42.5% (HR, 0.575; 95% CI, 0.409—0.808; P = .001) versus teriflunomide.
ASCLEPIOS I and II (NCT02792218 and NCT02792231) were identical in design, lasting up to 30 months and including 1882 participants at more than 350 centers in 37 countries. All patients were required to have an Expanded Disability Status Scale (EDSS) score between 0 and 5.5, with the ability to walk short distances without aid. In those assessments, 20-mg ofatumumab once monthly was associated with over a 50% reduction in annualized relapse rate in (ASCLEPIOS I: 50.5%; ASCLEPIOS II: 58.5%; P <.001 for both) compared with treatment with teriflunomide.2
It also significantly reduced inflammatory disease activity as demonstrated by the lack of gadolinium-enhancing T1 lesions and new or enlarging T2 lesions. Secondary outcomes were also met, including a 34.4% (P = .002) and 32.5% (P = .012) relative risk reduction in 3- and 6-month confirmed disability progression compared with teriflunomide.2
Earlier this year, at the 2020 America’s Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum, data from the open-label APLIOS study of ofatumumab were presented, which suggest that the treatment nearly completely depletes B cells over 12 weeks of treatment via an at-home autoinjector—bioequivalent to a prefilled syringe of the multiple sclerosis treatment. A few days prior to that presentation, the FDA accepted a supplemental biologics license application (sBLA) for ofatumumab, which was also simultaneously accepted for review by the European Medicines Agency.3
In a recent NeurologyLive Peer Exchange discussion, a panel of MS experts including another coauthor of these AAN data, Patricia K. Coyle, MD, among others, detailed some of the agents in development for multiple sclerosis, including data from the ASCLEPIOS I and II phase 3 trials of ofatumumab. Watch that conversation below.
For more AAN 2020 coverage, click here.
1. Montalban X, Cohen J, Comi G, et al. Ofatumumab Reduces Disability Progression Independent of Relapse Activity in Patients with Relapsing Multiple Sclerosis. Neurology. 2020;94 (15 Suppl). 1845.
2. Novartis ofatumumab demonstrates superiority versus Aubagio® in two head-to-head Phase III multiple sclerosis studies [press release]. Basel, Switzerland: Novartis; Published August 30, 2019. Accessed April 24, 2020. novartis.com/news/media-releases/novartis-ofatumumab-demonstrates-superiority-versus-aubagio-two-head-head-phase-iii-multiple-sclerosis-studies.
3. Novartis announces FDA and EMA filing acceptance of ofatumumab, a novel B-cell therapy for patients with relapsing forms of multiple sclerosis (RMS) [news release]. Basel, Switzerland: Novartis. February 24, 2020. Accessed April 24, 2020. globenewswire.com/news-release/2020/02/24/1988939/0/en/Novartis-announces-FDA-and-EMA-filing-acceptance-of-ofatumumab-a-novel-B-cell-therapy-for-patients-with-relapsing-forms-of-multiple-sclerosis-RMS.html.