Data from a pooled analysis of the phase 3 ASCLEPIOS I and II clinical trials suggest that patients with multiple sclerosis (MS) treated with ofatumumab have an increased likelihood of achieving no evidence of disease activity (NEDA-3) than those treated with teriflunomide (Aubagio; Sanofi).1
All told, the odds of achieving NEDA-3 status—defined as a composite of no 6-month confirmed disability worsening (6mCDW), no confirmed MS relapse, no new/enlarging T2 lesions, and no gadolinium-enhancing (Gd+) T1 lesions—were more than 3-fold higher for those administered ofatumumab from Months 0 to 12 (47%) compared to those taking teriflunomide (24.5%; odds ratio [OR], 3.36 [95%CI, 2.67–4.21]; P <.001). From Months 12 to 24, those odds increased to more than 8-fold higher for those on ofatumumab (87.8%) compared with teriflunomide (48.2%; OR, 8.09 [95%CI, 6.26–10.45]; P <.001).
The data were analyzed by Stephen L. Hauser, MD, director, UCSF Weill Institute for Neurosciences, and professor of neurology, UCSF School of Medicine, and colleagues, and were presented at the 2020 Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC 2020). The analysis included data on 927 patients from ASCLEPIOS I (NCT02792218) and 955 patients from ASCLEPIOS II (NCT02792231), and investigated the effect of subcutaneous ofatumumab 20-mg monthly compared with oral teriflunomide 14-mg once daily.
Additionally, treatment with Novartis’s fully human anti-CD20 monoclonal antibody was associated with a higher proportion of patients who were free from 6mCDW (91.9%), relapses (82.3%), and lesion activity (54.1%) compared to those on teriflunomide (6mCDW: 88.9%; relapses: 69.2%; lesion activity: 27.5%) over the 2-year period.
Ofatumumab also significantly reduced annualized relapse rate (ARR) compared with teriflunomide at all cumulative time intervals: Months 0-3 (P = .011), and all subsequent time intervals from Months 0-27 (P <.001). The Novartis product reported a significant reduction in the mean number of Gd+ T1 lesions per scan (95.9%; mean, 0.02 [95% CI, 0.01–0.03]) compared with teriflunomide (mean, 0.50 [95% CI, 0.42–0.59]; P <.001).
Another recent analysis of ofatumumab that was presented earlier this month at the American Academy of Neurology (AAN) annual meeting, also suggests that the therapy is superior in efficacy compared to teriflunomide in treating patients with relapsing MS. With regard to 3-month confirmed disability progression (CDP), those data showed that 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.2
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.
In February, the FDA accepted a supplemental biologics license application (sBLA) for ofatumumab for the treatment of relapsing forms of MS. The FDA originally assigned a PDUFA date of June 2020 for ofatumumab, but was pushed back to September 2020. It's not clear why the agency pushed back the decision date, though some speculated that the ongoing delays associated with the coronavirus disease 2019 pandemic may have contributed.3
At the time of the top-line data’s presentation at the European Committee for Treatment and Research in MS (ECTRIMS) 2019 meeting, Hauser told NeurologyLive that the effect size against the relapsing focal inflammation of MS in these analyses was “stunning” because the agent “can be self-administered by subcutaneous injection, rather than requiring an infusion," like many other options. He also noted that the adverse effect (AE) profile was difficult to distinguish from sham injections.
“One advantage is that patients and insurers are spared the cost of infusions, which can be extremely costly,” he added. “Also, because ofatumumab is a fully human molecule—the only fully human CD20—it is potentially better tolerated over the long term. The mode of administration is probably a formula that many patients will like; they can take the drug by themselves just once a month.”
1. Hauser SL, Bar-Or A, Cohen JA, et al. Ofatumumab Versus Teriflunomide in Relapsing Multiple Sclerosis: Analysis of No Evidence of Disease Activity (NEDA-3) from the ASCLEPIOS I and II Trials. Int J MS Care. 2020;22(2 Suppl). Late-Breaking Abstract.
2. 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.
3. Novartis provides update on FDA review of ofatumumab, a self-administered, targeted B-cell therapy for patients with relapsing multiple sclerosis. News release. Novartis. June 2, 2020. Accessed June 3, 2020. https://www.novartis.com/news/media-releases/novartis-provides-update-fd...