FDA Delays Ofatumumab Decision in Multiple Sclerosis


The anti-CD20 monoclonal antibody had an original PDUFA date of June 2020.

Stephen L. Hauser, MD

Stephen L. Hauser, MD

Novartis recently announced that the FDA has delayed its regulatory decision on ofatumumab, originally expected sometime this month, to September 2020.1 It’s not clear why the agency pushed back the decision date, though some have speculated that the ongoing delays associated with the coronavirus disease 2019 pandemic may have contributed.

“Novartis will continue to work with the FDA to complete the review as soon as possible,” said Marie-France Tschudin, president of Novartis, in a statement.1 “We are well prepared and ready to launch ofatumumab upon approval. We are committed to the MS community and look forward to bringing this important advancement to patients with MS.”

The fully human anti-CD20 monoclonal antibody is already approved in the US and Europe as first-line treatment for chronic lymphocytic leukemia (CLL) and recurring CLL. It is marketed under the name Arzerra.

The FDA accepted the supplemental biologics license application with priority review in February 20202 with data in hand from the head to head phase 3 ASCLEPIOS I and II trials,3 which included 1882 patients with multiple sclerosis (MS). The identical clinical studies compared once-monthly 20 mg subcutaneous ofatumumab with teriflunomide (Aubagio; Sanofi Genzyme), demonstrating over a 50% reduction in annualized relapse rate (P <.001) compared with the comparator drug. Treatment with ofatumumab was also associated with significant reductions in inflammatory disease activity as seen through the lack of gadolinium-enhancing T1 lesions or new or enlarging T2 lesions. In addition, patients treated with ofatumumab experienced a relative risk reduction of 34.4% and 32.5% in 3- and 6-month confirmed disability progression compared with teriflunomide.

Data recently presented at the 2020 ACTRIMS Forum from the open-label APLIOS study4 suggest that ofatumumab helps to nearly completely clear B-cell activity over 12 weeks of treatment with the at-home autoinjector. The 12-week study included 284 patients who were randomly assigned to receive 20 mg subcutaneous ofatumumab once per month administered via autoinjector (n = 128) or prefilled syringe (n = 130) to the abdomen or to the thigh (n = 13 for each). The participants received initial loading doses on days 1, 7, and 14, with monthly injections taking place from week 4 onwards. B-cell depletion was measured 9 times over the 12-week study.

At baseline, median B-cell counts ranged from 210 to 220 cells/μL. The investigators reported that the loading doses were associated with a rapid depletion of B cells, dropping to a median of 2 to 4 cell/μL by day 14, with sustained levels of ≤1 cell/μL by week 12. Low B-cell counts were achieved as early as day 14 in the majority of patients (77%-87%), increasing to 92% to 95% by week 4. Notably, these low levels were maintained through week 12 in 97% to 100% of patients.

“The results suggest that ofatumumab sc offers an effective B-cell depleting therapy using the patient-friendly AI SensoReady pen that allows for monthly at-home self-administration and can help reduce treatment burden,” the study authors concluded.4

Additional findings from the phase 3 ASCLEPIOS I and II trials presented at the 2020 CMSC Annual Meeting5 demonstrated that treatment with ofatumumab was associated with a 3-fold higher odds of achieving no evidence of disease activity-3 (NEDA-3) status over 12 months of treatment compared with teriflunomide (odds ratio 3.36; 95% CI, 2.67—4.21; P <.001). Over an additional 12 months of treatment, those odds increased to more than 8-fold higher for those taking ofatumumab.

“One advantage is that patients and insurers are spared the cost of infusions, which can be extremely costly,” study investigator Stephen L. Hauser, MD, director of the University of California, San Francisco (UCSF) Weill Institute for Neurosciences and professor of neurology at UCSF School of Medicine, told NeurologyLive in a previous interview. “Also, because ofatumumab is a fully human molecule—the only fully human CD20&mdash;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. 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-fda-review-ofatumumab-self-administered-targeted-b-cell-therapy-patients-relapsing-multiple-sclerosis

2. 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. Novartis. February 24, 2020. Accessed February 24, 2020. https://www.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

3. Novartis ofatumumab demonstrates superiority versus Aubagio® in two head-to-head Phase III multiple sclerosis studies. News release. Novartis. August 30, 2019. Accessed September 5, 2019. novartis.com/news/media-releases/novartis-ofatumumab-demonstrates-superiority-versus-aubagio-two-head-head-phase-iii-multiple-sclerosis-studies

4. Bar-Or A., Fox E, Goodyear A, et al. Onset of B-cell depletion with subcutaneous administration of ofatumumab in relapsing multiple sclerosis: results from the APLIOS bioequivalence study. Presented at: 2020 ACTRIMS Forum. Abstract LB300.

5. 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.

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