Ofatumumab Lowers B-cell Counts and Helps Relapsing MS Patients Reach NEDA, Data Show

Ofatumumab (OMB157) elicits a strong and fast reduction in the levels of circulating immune cells in people with relapsing forms of multiple sclerosis (MS), effectively helping to stop disease activity, according to new data from the Phase 2 APLIOS trial.

The medication was also found to be more effective than Aubagio (teriflunomide) at eliminating all signs of MS activity in a post-hoc analysis of the two Phase 3 ASCLEPIOS trials.

These new findings were recently presented virtually during the 6^th Congress of the European Academy of Neurology (EAN), and published in the European Journal of Neurology.

They further support ofatumumab, under regulatory review in the U.S. with a decision expected in June, as a potential treatment option for relapsing forms of MS.

Ofatumumab, co-developed by Genmab and Novartis, is a fully human antibody that specifically targets and blocks the activity of CD20, a protein receptor found on the surface of immune B-cells. These immune cells are thought to drive the damaging immune responses against myelin — the fatty substance that wraps around nerve fibers to ensure proper nerve cell communication — seen in MS patients.

By blocking CD20, ofatumumab is expected to lower the number of circulating B-cells and possibly limit their interactions with other immune cells, which are key in MS progression.

Requests for its approval are before both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), with an FDA decision likely to be announced in the coming weeks, and that of the EMA expected next year.

If approved, ofatumumab will be the first B-cell therapy that patients can give themselves at home using an autoinjector pen, called SensoReady.

During the EAN Congress, Novartis presented data from a new analysis of APLIOS (NCT03560739), a global 12-week, open-label Phase 2 trial that investigated the pharmacological properties of ofatumumab when administered with two different devices: a prefilled syringe and the SensoReady pen.

Previous results from APLIOS showed that both subcutaneous (under the skin) delivery devices had similar effects on patients’ B-cells, and reasonable safety.

The new data, presented in the poster “Effect of Subcutaneous Ofatumumab on Lymphocyte Subsets in Patients with RMS: Analysis from the APLIOS Study” (note: EAN registration is needed to access abstracts and posters), detailed findings on the 284 adults with relapsing-remitting multiple sclerosis (RRMS) or active secondary progressive multiple sclerosis (SPMS) who participated in the trial.

Results showed that ofatumumab, given subcutaneously at a dose of 20 mg once a month, rapidly lowered levels of CD20-positive B- and T-cells. These rapid and sustained reductions were apparent in several subsets of immune cells, including memory and naïve B-cells, as well as highly active killer T-cells.

In B-cells, significant reductions became apparent by day 14, and were maintained up to day 84 (about 12 weeks). Reductions in T-cell levels  became apparent sooner (days 4–7) and rose slightly at day 84.

In the oral presentation “Early Effect of Ofatumumab on B-cell Counts and MRI Activity in Relapsing Multiple Sclerosis Patients: Results from the APLIOS Study,” researchers presented additional data from APLIOS showing ofatumumab reduced the average number of MS lesions — from 1.5 at baseline (study start) to 0.1 by week 12, and increased the percentage of patients who remained lesion-free over the course of the study — from 64.2% at baseline to 94.1% by week 12.

Novartis also presented data from a post-hoc analysis of two Phase 3 trials — ASCLEPIOS I (NCT02792218) and ASCLEPIOS II (NCT02792231) — focused on assessing the odds of RRMS or SPMS patients using ofatumumab achieving a disease-free state.

Findings from this analysis, based on data covering 1,882 patients, were in poster “Ofatumumab vs Teriflunomide in Relapsing Multiple Sclerosis: Analysis of No Evidence of Disease Activity (NEDA-3) from ASCLEPIOS I and II Trials.”

Previous data from ASCLEPIOS showed that ofatumumab lowered relapse rates and active brain lesions in people with relapsing MS.

New data presented at EAN showed that compared with Aubagio, an approved MS medication marketed by Sanofi, ofatumumab increased a patient’s likelihood of achieving a disease-free state based on NEDA-3 (no evidence of disease activity) — defined as no relapses, no six-month worsening in confirmed disability, and no new or active MS lesions.

Within the first year of treatment, nearly half (47.0%) of the patients receiving ofatumumab — and a fourth (24.5%) of those given Aubagio — attained NEDA-3. In the second year, the percentage of ofatumumab-treated patients attaining a disease-free state was almost double that seen in the Aubagio group — 87.8% with ofatumumab versus 48.2% with Aubagio.

“Achieving no evidence of disease activity is widely recognized as an important treatment goal for multiple sclerosis therapies. These data suggest that halting new disease activity is possible by targeted B-cell therapy,” Ludwig Kappos, MD, the study’s senior author, said in a press release.

In another oral presentation, “Effect of Ofatumumab on B-cell Depletion and Efficacy Outcomes: Subgroup Analysis from the Pooled Phase 3 ASCLEPIOS I and II Trials,” investigators presented additional findings from a subgroup analysis of pooled data from both ASCLEPIOS trials.

Compared with Aubagio, ofatumumab led to stronger reductions in B-cell counts, independent of patients’ body weight. Additionally, ofatumumab showed greater efficacy than Aubagio at reducing disability worsening and the number of MS relapses that patients experienced within a year.

“These results are encouraging and support our belief that, if approved, ofatumumab could have the potential to significantly improve the lives of people with RMS [relapsing MS],” said Krishnan Ramanathan, head of the Neuroscience Global Program at Novartis.

While waiting for the FDA’s decision regarding ofatumumab’s potential approval in the U.S., the company is preparing requests for its approval by regulatory authorities elsewhere.